Skip Navigation

Serotype Diversity and Reassortment between Human and Animal Rotavirus Strains: Implications for Rotavirus Vaccine Programs

  1. Jon R. Gentsch1,
  2. Ashley R. Laird1,
  3. Brittany Bielfelt1,
  4. Dixie D. Griffin1,
  5. Krisztián Bányai2,
  6. Madhu Ramachandran1,
  7. Vivek Jain1,
  8. Nigel A. Cunliffe3,
  9. Osamu Nakagomi4,
  10. Carl D. Kirkwood5,
  11. Thea K. Fischer1,
  12. Umesh D. Parashar1,
  13. Joseph S. Bresee1,
  14. Baoming Jiang1 and
  15. Roger I. Glass1
  1. 1 Respiratory and Enteric Viruses Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
  2. 2 Regional Laboratory of Virology, Baranya County Institute of State Public Health Service, Pécs, Hungary
  3. 3 Department of Medical Microbiology and Genito-Urinary Medicine, University of Liverpool, Liverpool, United Kingdom
  4. 4 Nagasaki University Graduate School of Biomedical Sciences Sakamoto, Nagasaki, Japan
  5. 5 Murdoch Children's Research Institute, Royal Children's Hospital, Victoria, Australia
  1. Reprints or correspondence: Dr. Jon R. Gentsch, Respiratory and Enteric Viruses Branch, MS G-04, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Atlanta, GA 30333 (jrg4{at}cdc.gov).
 
Next Section

Abstract

The development of rotavirus vaccines that are based on heterotypic or serotype-specific immunity has prompted many countries to establish programs to assess the disease burden associated with rotavirus infection and the distribution of rotavirus strains. Strain surveillance helps to determine whether the most prevalent local strains are likely to be covered by the serotype antigens found in current vaccines. After introduction of a vaccine, this surveillance could detect which strains might not be covered by the vaccine. Almost 2 decades ago, studies demonstrated that 4 globally common rotavirus serotypes (G1–G4) represent >90% of the rotavirus strains in circulation. Subsequently, these 4 serotypes were used in the development of reassortant vaccines predicated on serotype-specific immunity. More recently, the application of reverse-transcription polymerase chain reaction genotyping, nucleotide sequencing, and antigenic characterization methods has confirmed the importance of the 4 globally common types, but a much greater strain diversity has also been identified (we now recognize strains with at least 42 P-G combinations). These studies also identified globally (G9) or regionally (G5, G8, and P2A[6]) common serotype antigens not covered by the reassortant vaccines that have undergone efficacy trials. The enormous diversity and capacity of human rotaviruses for change suggest that rotavirus vaccines must provide good heterotypic protection to be optimally effective.

Globally, rotavirus infection is the most important cause of severe diarrhea in children. Most deaths occur in less-industrialized countries [1], and health organizations worldwide are promoting the development of rotavirus vaccines to help control this disease. The current strategy is based on the use of live, attenuated rotavirus vaccine candidates designed to elicit immunity comparable to that induced by natural rotavirus infections by providing homotypic or heterotypic protection against severe diarrhea caused by the major rotavirus serotypes in circulation [2]. The earliest vaccine candidates were individual animal rotaviruses with serotypes that were usually distinct from those of common human strains. Although these candidate vaccines provided good heterotypic protection in some vaccine trials, in other trials, they either failed to provide protection or provided the best protection only when the serotype of the animal strain matched that of the infecting human strain [3]. These results suggested that serotype-specific immunity might play an important role in protection against rotavirus gastroenteritis. This notion prompted the development of vaccine candidates based on human strains and human-animal reassortants containing the common serotype antigens of human strains. Over the past 2 decades, studies of the burden of rotavirus disease and strain surveillance in many countries have assessed the need for rotavirus vaccines and have determined the most important human rotavirus (HRV) serotypes that should be targeted by candidate vaccines.

In this report, we review the results of strain surveillance and characterization studies published through early 2004 and discuss new insights gained from these studies on the potential mechanisms of the evolution and spread of new rotavirus strains. Although other recently published articles have reviewed the strain diversity and genetic and antigenic variation of rotavirus, our aim is to provide a profile of strains that could potentially affect rotavirus vaccine programs [4–6].

Previous SectionNext Section

Rotavirus Structure and Serotypes

Rotaviruses, which comprise a genus of the Reoviridae family, have a capsid with 3 protein layers that encase a genome with 11 segments of double-stranded RNA (dsRNA) (figure 1) [7]. Each segment usually codes for a single structural or nonstructural protein. The inner layer encasing dsRNA is composed of the VP2 protein and small numbers of the VP1 and VP3 proteins, which are associated with the genomic RNA. This core is surrounded by the middle protein layer, which is composed entirely of VP6, the antigen that defines group and subgroup (SG) specificities. The outer capsid layer consists of the VP7 glycoprotein layer, in which VP4 spikes are embedded. The 2 outer capsid proteins carry rotavirus serotype (neutralization)-specific antigens and are encoded by segments 4 (VP4 protease-sensitive protein and P serotype antigen) and by segments 7, 8, or 9 (VP7 glycoprotein and G serotype antigen). Because the VP4 and VP7 proteins are encoded by separate gene segments, rotaviruses can generate new P-G serotype antigen combinations through reassortment after dual infection of single cells. Because both serotype antigens are believed to be key in the development of protective immunity, it is necessary to assess their prevalence and to study genetic and antigenic variation for both G and P serotypes. Although there is good evidence from animal experiments that passively transferred VP7- and VP4-specific antibodies protect separately, it is less clear which component of the immune response is most important for protection after natural infection or vaccination [8].

Figure 1
View larger version:
Figure 1

Rotavirus structure showing protein coding assignments of 11 genome RNA segments (left). Schematic diagram (middle) and cryoelectron microscopic reproduction of a virion (right) show the location of major structural proteins. NSP, nonstructural protein. Reproduced with permission from Estes [7].

At least 10 G serotypes and 11 P serotypes and subtypes of HRV have been identified. Because identification of P serotypes is technically difficult, usually, only the corresponding VP4 genes are identified by genotyping methods in surveillance studies. To distinguish strains that have been identified by genotyping only from those identified by P-serotyping, a dual nomenclature is used. P genotypes are expressed as “P,” followed by a number in brackets (e.g., P[6]), whereas P serotypes are designated by “P” with a serotype number, followed by the corresponding genotype in brackets (e.g., P2A[6]) [7].

Rotaviruses can also be classified according to their VP6 SG specificity (I or II), by use of an EIA with monoclonal antibodies (MAbs) or by nucleotide sequencing of a VP6 gene fragment [9, 10], and according to their RNA profile (long or short electropherotype), by use of acrylamide gels and on the basis of the migration rate of gene 11. The short-electropherotype phenotype results from a partial duplication in gene 11, which causes it to migrate more slowly than gene segment 10, whereas the standard-sized gene 11 of long-electropherotype strains migrates faster than segment 10 [11].

The most common HRV strains belong to 2 distinct genome constellations (genogroups) that are only minimally related, as determined by high-stringency hybridization procedures performed with whole-genome probes [12, 13]. Strains of the Wa genogroup typically have long electropherotypes and carry the SG II antigen, whereas members of the DS-1 genogroup usually have short electropherotypes and carry the SG I antigen.

Serotypes are defined by neutralization studies, and the immune targets are usually located in the outer capsid. During the early 1980s, the first data on the distribution of rotavirus serotypes were obtained through cultivation of the most common isolates found in stool samples and their characterization in cross-neutralization studies by use of antisera that were hyperimmune to the individual strains [14]. These studies identified 4 common serotypes, now designated serotypes G1–G4, that corresponded to antigenic determinants located on the VP7 protein. Studies of animal models subsequently demonstrated that VP7 played an important role in protective immunity [15, 16]. On the basis of these pioneering studies, the 4 commonly identified G serotypes were chosen for incorporation into early and current reassortant vaccine candidates. The subsequent development of EIA methods for direct typing of rotaviruses in stool samples, by use of serotype-specific MAbs [17, 18], allowed for large-scale epidemiologic studies that documented the global incidence of those 4 original serotypes (reviewed elsewhere [19, 20]) (figure 2, left panel). In those studies, serotype G1 represented approximately half of the strains globally, followed by serotypes G3, G4, and G2 [19, 20]. Overall, MAb serotyping data suggested that serotypes G1–G4 represented at least 90% of strains circulating globally and needed to be targeted by candidate vaccines. Typically, ∼30% of rotavirus-positive stool specimens cannot be typed with MAbs and are, thus, designated as nontypeable (NT) strains [21]. Characterization of NT strains by cultivation and by antigenic and molecular analysis led to the identification of several new HRV serotypes (G8, G9, and G12). Thus, by 1990, there were 7 different HRV G types, although types G8, G9, and G12 were considered to be rare [22–25].

Figure 2
View larger version:
Figure 2

Findings from typing studies conducted during 1987–1991 that used G serotype-specific monoclonal antibodies (left panel; data are adapted from Woods et al. [19]) or that used G-serotyping and P-genotyping or G- and P-genotyping (right panel). The “other” category in the chart of P and G types refers to strains that were nontypeable (NT) for P type, G type, or P and G type, or were mixed infections of common P or G types.

The serotypes of rotavirus needed to be reconsidered when VP4, the other outer capsid protein, was identified as an independent serotype antigen (P serotype) by sequencing of VP4 genes from strains with different G serotypes and by neutralization studies [15, 26, 27]. P serotypes were also shown to be important for protective immunity by studies of animal models in which reassortants containing HRV P serotypes and animal rotavirus G serotypes were used [28]. However, serotyping was a challenge in the absence of a collection of MAbs specific for the diversity of P serotypes. Although MAbs to several common P serotypes were identified, cross-reactivity between the types precluded their use for routine P serotyping [29, 30].

New methods that greatly facilitated strain surveillance studies, including reverse-transcription polymerase chain reaction (RT-PCR) genotyping and automated nucleotide sequencing, have been widely used for this purpose since the early 1990s. A multiplexed, seminested RT-PCR method to identify G serotypes by genotyping [31] permitted the detection of both the common serotypes (G1–G4) and the rare serotypes (e.g., G8 and G9) for which EIA-based serotyping antibodies were either not available or not in routine use. Finally, these multiplexed RT-PCR methods were extended to permit genotyping of the other major neutralization protein, the P protein (VP4) [32, 33]. As for G-genotyping, common P types (P[4] and P[8]) and newly identified rare P types (P[6], P[9], and P[10]) could be detected. Analogous hybridization methods for genotyping were also developed [34, 35].

In 8 countries, initial surveillance studies conducted with G- and P-genotyping or with G-serotyping and P-genotyping again showed the presence of 4 common types (described in depth elsewhere [36]). In agreement with earlier molecular and antigenic characterization of culture-adapted prototype G1–G4 strains isolated from children with diarrhea, most G1, G3, and G4 isolates found in stool specimens were of genotype P[8], with SG II specificity and long electropherotypes, whereas G2 strains were of genotype P[4], with SG I specificity and short electropherotypes. Surprisingly, these studies also detected 10 uncommon reassortants, including rare P types (P[3], P[6], and P[9]) and G types (G5), at a combined prevalence of ∼3%, suggesting that earlier studies in which serotyping was used alone underestimated strain diversity. This notion proved to be true as expanded surveillance studies, especially those conducted in developing countries where surveys were not previously performed, yielded many examples of unexpected G and P genotypes.

Previous SectionNext Section

Review of Studies

We have reviewed the global distribution of rotavirus strains as documented by studies of rotavirus diarrhea conducted in 35 countries and involving >21,000 HRV strains. Studies were included in our review if they were published in the English language through January 2004 and if they reported G and P type combinations. These studies usually used RT-PCR genotyping exclusively, but some used a combination of G-serotyping and RT-PCR (figure 2) [37–105]. The 4 common strains—P[8]G1, P[4]G2, P[8]G4, and P[8]G3—represent almost 72% of all strains, and >2% consist of 2 reassortants of the recently emerged serotype G9 (P[8]G9 and P[6]G9). Strains in the “other” category typically included mixed infections with globally common types and those that could not be typed for P or G genotype or for both P and G genotype. Approximately 6% of typeable strains are composed of 25 other P-G combinations types (figure 2, right panel).

A number of studies showed striking examples of strain diversity that, together, demonstrated the importance of serotypes other than G1–G4 as a cause of gastroenteritis in children. These studies included the detection of P[8]G5 in Brazil, P[6]G8 and P[4]G8 in Malawi, and P[6]G9 in India (figure 3). Although G5 and G8 do not appear to be globally important (figure 4), they are clearly of major importance in Brazil and Malawi [40, 95, 106]. Serotype G8 may also be epidemiologically important in other parts of Africa [107]. When a high prevalence of the P[6]G9 strain was detected in India (figure 3), it was still believed to be rare elsewhere and, thus, was considered to be only regionally common [41]. However, a recent compilation of surveillance studies performed since 1995, including many not reviewed here because they did not report P-G genotype combinations, indicated that G9 emerged as early as 1993 to become 1 of 5 important serotypes globally, with a prevalence of at least 5.8% through the end of 2001 [108]. When recent studies showing a countrywide prevalence as high as 40% are included, the estimate of G9 prevalence is likely to increase substantially [109].

Figure 3
View larger version:
Figure 3

Examples of regionally important strains from India (n = 133) [41, 42], Malawi (n = 100) [53], and Brazil (n = 130) [40]

Figure 4
View larger version:
Figure 4

Reassortants of human rotavirus P and G serotypes, including uncommon and regional strains isolated from children with diarrhea

To try to develop a current picture of strains that have the highest potential to affect rotavirus vaccination programs, we summarized the most important P-G combination types detected in surveillance studies conducted since 1996 that analyzed at least 50 strains (table 1). Strain types that had an overall incidence of <0.5% are listed in the note to table 1. Five strains, including the P[8]G9 strain, were considered to be globally common on the basis of overall prevalence. Although the P[6]G9 strain was detected first, as the emergence of G9 began around 1995, more recent studies suggested that the P[8]G9 strain may be predominant [90, 110]. At least 6 regionally common strains, including P[8]G5, P[6]G8, and P[6]G9, with a prevalence of at least 0.5%, are circulating among children. Of note, P[6] strains, which were previously identified as the third most prevalent P type [5], represented >5% of the circulating strains in 30 of 47 studies reviewed (data not shown). Genotyping studies conducted in 11 of 12 African countries (not reviewed here) documented a prevalence of 18%–75% for the P[6] strain, which suggests that the average global prevalence may prove to be substantially higher as more surveys are completed in Africa and Asia [107]. Finally, strains with G types other than the common ones (G1–G4 and G9), including G5, G6, G8, and G10 in various combinations with P[4], P[6], P[8], P[9], and P[14] types, made up ∼1.2% of the total.

View this table:
Table 1

Summary of rotavirus P- and G-genotyping studies conducted since 1996.

When overall strain incidence was compared with the incidence in studies conducted in different continents, several differences are obvious. The most striking difference is the higher incidence of P[6] strains in Latin America, Africa, and Asia, compared with that in more-industrialized areas, such as Europe and North America. In addition, the incidence of unusual strains (e.g., P[4]G1 and P[4]G3) is often higher in developing countries. Finally, as mentioned above (figure 3), the regional importance of some strains (e.g., P[6]G8 in Malawi and P[6]G9 in India) is illustrated.

Previous SectionNext Section

Discussion

The introduction of molecular typing methods has enhanced our understanding of the diversity of rotavirus strains that affect both the development of rotavirus vaccines and our understanding of viral evolution. This review of >21,000 strains from 35 countries provides several new insights.

Common Strains

These studies confirmed the continued importance of serotypes G1–G4. Globally, >90% of single fully typeable strains bear these VP7 antigens, and only Africa had an incidence of <90% (i.e., 86%) for these serotypes.

Increased Strain Diversity

Studies conducted before 1990 suggested that only 4 common serotypes accounted for virtually all rotavirus strains circulating among children. Since then, along with the widespread application of RT-PCR genotyping and molecular methods, strain surveillance and characterization studies have led to the identification of at least 42 distinct P-G type combinations among the 10 HRV G serotypes and 11 HRV P serotypes and subtypes, representing more than one-third of the 110 theoretically possible P-G combinations (figures 2, 3, and 4) [26, 111–129]. In addition to the original 4 strains, at least 8 other globally or regionally common strains have been described that, overall, contain 4 additional serotype antigens (G5, G8, G9, and P[6]) and that are not included in the polyvalent rotavirus vaccine currently in development. This number is likely to increase as surveillance studies continue. Many of the 42 strains, including several that are epidemiologically important, appear to have been formed by the introduction of a new serotype antigen gene into a common HRV strain (e.g., the introduction of G8 and G12 VP7 genes into DS-1 genogroup strains) [111, 113]. Other strains may have arisen by interspecies transmission or by reassortment between human and animal rotaviruses [130, 131]. The finding of this enormous diversity among rotavirus strains provides insights into the evolution of rotavirus strains [4, 5, 132] and creates new challenges for rotavirus vaccine programs.

Vaccines currently in the late stages of development include one based on a monovalent serotype P1A[8]G1 HRV strain (Rotarix; GlaxoSmithKline) and another based on a pentavalent bovine-human reassortant strain containing G1–G4 and P1A[8] antigens (RotaTeq; Merck) [133, 134]. Rotarix is based on the concept that infection with 1 HRV serotype may elicit heterotypic protection as a result of cross-reactive antigens between serotypes, whereas RotaTeq is based on serotype-specific immunity and, in theory, should contain the antigens of the most common HRV strains to achieve optimal protection. Thus, one major challenge for the RotaTeq vaccine will be to protect effectively against the globally (G9) or regionally (G5 and G8) common G serotypes that have been identified by strain surveillance in recent years but that are not present in the vaccine. Although RotaTeq might be expected to provide a measure of protection against some of these strains (e.g., P[8]G5 and P[8]G9) because of shared P serotype antigens, other strains (e.g., P[6]G9 and P[6]G8) share neither serotype antigen and, thus, may offer the biggest challenge to this vaccine. On the other hand, the Rotarix vaccine may work well against strains that have different serotypes but many cross-reactive antigens (e.g., strains in the same [Wa] genogroup: P[8]G9 and P[8]G3), but the vaccine may be challenged by short-electropherotype P[4]G2 and P[6]G9 strains that not only have distinct serotype antigens but also belong to a completely unique genogroup (DS-1) from the Rotarix strain and, thus, have fewer cross-reactive antigens. Consequently, it will be important to determine from vaccine trials of these 2 candidates whether they elicit immunity against strains that may challenge their protection mechanism [4]. In this regard, available vaccine trial data for Rotarix show that it provides cross-protection against P[8]G9 strains, but it is not yet known whether it protects against P[4]G2 strains of the DS-1 genogroup [135].

Mechanisms of Rotavirus Evolution

In addition to the challenges posed for rotavirus vaccine programs, the great diversity observed in studies of rotavirus strain surveillance and characterization provides insights into the genetic variation and spread of rotavirus strains. Rotaviruses evolve by point mutations, gene rearrangements of primarily nonstructural genes, and reassortment events, all of which have long been known [5, 136]. An intermolecular recombination of rotavirus has been described once [137].

Reassortment

Reassortment between the common strains detected in surveillance studies is well documented. The globally common genotype P[8] strains with serotype G1, G3, G4, or G9 VP7 genes belong to the same genome constellation (Wa genogroup), as indicated by the ability of all genes, except VP7, to cross-hybridize with other genogroup members [13]. The fifth globally common strain, P[4]G2, belongs to a distinct genome constellation (DS-1 genogroup) that does not cross-hybridize with any gene segment from typical members of the Wa genogroup. Nucleotide sequencing studies provided strong evidence that reassortment occurs between circulating genotype P[8] strains with G1, G3, G4, or G9 specificity when it was found that phylogenetically distinct VP4 genes of such strains can segregate with VP7 genes of >1 G serotype [138, 139]. Other sequencing studies demonstrated that all 11 genes reassorted between typical long-electropherotype G1 and G4 strains. When fragments of each gene of cocirculating G1 and G4 strains were sequenced, it was found that the cognate genes from the 2 serotypes could be distinguished phylogenetically. Subsequently, it was shown that the distinct lineages of each gene could be identified in both serotypes, demonstrating that reassortment occurs in all 11 gene segments of such strains [140]. Together, these studies show that reassortment is a major evolutionary mechanism in common circulating rotavirus strains.

In contrast to the high level of multigenic reassortment that is believed to occur between members of the same genogroup (designated “intragenogroup reassortment”), independent segregation of genes between the major HRV genogroups (designated “intergenogroup reassortment”) is uncommon overall. The evidence, in part, comes from early studies showing that the G types of commonly circulating strains are usually associated with a single P type, SG, and electropherotype [36]. These data confirmed earlier investigations conducted by use of PAGE analysis, subgrouping, and whole-genome hybridization of partially restricted exchange of gene segments between strains in the 2 main rotavirus genome constellations (Wa and DS-1 genogroups) [13]. However, more-complete surveillance studies have documented numerous examples of the reassortment of serotype antigen genes across genogroups, and single G types have been detected in association with a wide variety of P types. The global incidence of these reassortants is low (<10%), but it is clear that they can be very common in some settings; P[6]G9 is common among both Wa genogroup and DS-1 genogroup strains [108]. Numerous examples of intergenogroup reassortment in other genes are also well documented [141–144].

The generation of new P-G genotype combinations by the introduction of genes from novel serotypes represents another mechanism for the generation of rotavirus diversity. Sequencing studies of the VP7 gene of emerging serotype G9 strains detected around 1995 demonstrate that the VP7 gene is distinct from the cognate gene of G9 strains first isolated in the United States a decade previously [23]. This result indicates that the modern lineage is not directly descended from the original lineage, and may, instead, be the result of a recent introduction into humans through reassortment [145, 146].

In children with diarrhea, the modern G9 VP7 gene lineage was first detected among long-electropherotype P[8]G9 strains during the 1994–1995 rotavirus season in Japan and among P[4]G9, P[6]G9, and P[8]G9 strains over the next several years in other countries [62, 145–149]. Hybridization studies indicate that these strains represent 2 distinct genotypes, P[8]G9 and P[6]G9, which were single-segment reassortants of typical members of the Wa and DS-1 genogroups, respectively [108]. The same G9 lineage was subsequently shown to be present as early as 1993 in Indian neonates, who excreted a long-electropherotype P[6]G9 strain in the absence of symptoms of diarrhea [108]. Thus, it is plausible that these unusual neonatal infections could have been an early source for the spread of this gene to children with diarrhea, from which it subsequently spread globally and reassorted to produce a variety of new genotypes.

Interspecies transmission

Another major source of HRV diversity involves the introduction of animal rotavirus genes either through transmission of whole viruses or through reassortment. Evidence for the first of these mechanisms came from hybridization studies that used whole-genome probes made from HRV strains by in vitro transcription. For example, all 11 segments of several HRVs (e.g., AU-1, P3[9]G3, and HCR-3 P5A[3]G3 strains) are virtually indistinguishable from feline and canine strains with the same serotype, suggesting that these uncommon strains with novel P serotypes were derived through interspecies transmission to humans [130, 131]. However, only a few strains have high homology to all 11 genes of animal rotaviruses, suggesting that interspecies transmissions that result in gastroenteritis are rare.

Animal-HRV reassortment

A more common mechanism for the introduction of animal rotavirus genes into HRVs is through reassortment. Examples of both rare (e.g., G6, G8, P3[9], and P5A[3]) and common (e.g., G3, G4, and P1A[8]) P and G HRV serotypes (figure 4) that have very close genetic and antigenic relationships with the same rotavirus serotype in animals are well known. Especially intriguing are recent findings that, when some common HRV G serotypes (G3 and G4) and P serotypes (P1A[8]) are sequenced, they are almost indistinguishable from the same genes in porcine or canine rotavirus strains, which suggests that even common HRV serotypes may have recent animal origins [150]. Whole-genome hybridization experiments and nucleotide sequencing show that animal-human reassortants may contain only a serotype antigen gene (e.g., strain 116E) or several genes related to animal rotaviruses [151, 152]. In the case of strain 116E, the VP4 gene is highly related to the bovine serotype P8[11]G10 VP4 gene, whereas the remaining 10 genes are related to typical HRV strains of the Wa genogroup (e.g., P1A[8]G1, SG II, long electropherotype) [121]; strain I321 (P[11]G10) contains 2 genes from HRVs of the Wa genogroup, and its remaining genes are from a bovine rotavirus [152]. Some of the G5 strains isolated in Brazil, such as Br1054 (P[8]G5), contain several genes each from human Wa genogroup strains and porcine rotaviruses related to the serotype G5 isolate, OSU [153]. Other uncommon strains, such as PA151 (P3[9]G6) and PCP5 (P3[9]G3), which were isolated in Italy, have the same P serotype as feline rotaviruses and the felinelike HRV strain AU-1. Unlike AU-1, these strains are apparent reassortants, deriving several genes each from bovine rotaviruses and AU-1-like rotaviruses [154]. Strains that have the same numbers of bovine and HRV genes or the same P and G types as PA151 and PCP5 have been detected in the United States and Hungary [113, 155]. The finding of such close sequence similarity in these geographically and temporally diverse strains suggests that they possibly share a common origin. These strains may have entered the human population at least once or more and subsequently may have acquired a G3 VP7 gene through reassortment with a human G3 rotavirus [113, 126].

A variety of other HRVs with strong associations with animal strains have been reported. The serotype G8 strain 69M (P4[10]G8), which has a supershort electropherotype pattern, contains genes related to HRVs of the DS-1 genogroup and others related to typical bovine rotaviruses [156]. Long-electropherotype G8 strains (e.g., Hal1166 and other P[14]G8 isolates) from a variety of settings share similar relatedness to the human DS-1 genogroup and bovine rotaviruses, but they also share a high homology to the typically lapine VP4 gene (P[14]), which suggests that such strains could have been derived through reassortment events in 2 different animal species [125, 156–158].

Mixed infections

The great degree of strain diversity among rotaviruses, particularly in some developing countries, suggests that, for children, coinfections with 2 different rotavirus serotypes may be a relatively frequent occurrence. In fact, mixed infections with rotavirus strains appear to be quite common in some settings in developing countries, on the basis of studies showing 2 RNA profiles in the same patient specimens and on the basis of results of RT-PCR genotyping and EIA serotyping studies that demonstrated the presence of >1 genotype or serotype in the same stool sample [36, 132, 159]. In strain prevalence surveys, the highest levels of detection of mixed infections are often in developing countries, where higher numbers of different genotype combinations have been detected (figures 3 and 5) [41, 51, 99, 160]. In India, for example, multicenter surveys identified as many as 9 P-G genotype combinations among rotavirus specimens collected in a single city [41, 64]. In contrast, in studies conducted in developed countries, fewer mixed infection were seen, and fewer genotype combinations were detected per city surveyed (figure 5) [36]. Thus, the high levels of detection of mixed infection in children with diarrhea, especially in developing countries, may play a major role in generating strain diversity.

Figure 5
View larger version:
Figure 5

Differences in the incidence of mixed infections in developed versus developing countries. Data are adapted from the following references: [36, 40, 41, 97–99, 101–103, 105, 159]. BAN, Bangladesh; BRA, Brazil; IND, India; JPN, Japan; Malay, Malaysia; S. Afr, South Africa; USA, United States of America.

Role of neonates

Another intriguing possibility is that mixed infections in neonates could be an important source of novel rotavirus strains. It has been known since the 1970s that strains with common G serotypes and genogroups and novel P serotypes (P2A[6]) circulated in hospital nurseries, often without producing symptoms of diarrhea [161]. These strains sometimes circulated continually in the same nursery for years and thus served as an uninterrupted reservoir where mixed infections could potentially occur any time another strain was introduced by staff or visitors. Although, at first, they were thought to be confined to neonates, P[6] strains are relatively common in children with diarrhea, suggesting that reassortment in neonates could be one possible source for new strains. Strains undergoing reassortment in neonates could explain the origin of other HRVs as well. As noted, the VP7 gene of novel P[6]G9 strains was first detected in infected neonates by sequence analysis. The same VP7 gene lineage is now common in children with gastroenteritis.

The novel P2A[6]G8 strains that are common in Malawi were detected in neonates and children with diarrhea in Malawi at approximately the same time [53, 162]. Two distinct P8[11] strains with G9 or G10 specificity were first detected in neonates [163, 164]. The P[11]G10 strains are now common in children with diarrhea in some parts of India, whereas a P[11]G4 reassortant is detected infrequently in sick Indian children [42, 165].

Previous SectionNext Section

Acknowledgment

We thank Claudia Chesley for her help in editing the paper.

Previous SectionNext Section

Footnotes

  • Financial support: Centers for Disease Control and Prevention.

  • Potential conflicts of interest: none reported.

  • Addendum. Since this manuscript was accepted for publication, another review of the global distribution of rotavirus strains and its possible effect on rotavirus vaccines has been published [166].

Previous Section
 

References

  1. ↵
    1. Miller MA,
    2. McCann L
    . Policy analysis of the use of hepatitis B, Haemophilus influenzae type B-, Streptococcus pneumoniae-conjugate, and rotavirus vaccines, in national immunization schedules. Health Econ 2000;9:19-35.
    CrossRefMedlineWeb of Science
  2. ↵
    1. Howley PM
    1. Kapikian AZ,
    2. Hoshino Y,
    3. Chanock RM
    . Rotaviruses. In: Howley PM, editor. Fields virology. 4th ed. Vol. 2. Philadelphia: Lippincott, Williams & Wilkins; 2001. p. 1787-833.
    Abstract/FREE Full Text
  3. ↵
    1. Perez-Schael I,
    2. Blanco M,
    3. Vilar M,
    4. et al
    . Clinical studies of a quadrivalent rotavirus vaccine in Venezuelan infants. J Clin Microbiol 1990;28:553-8.
    Abstract/FREE Full Text
  4. ↵
    1. Cunliffe N,
    2. Bresee J,
    3. Gentsch J,
    4. Glass R
    . The expanding diversity of rotaviruses. Lancet 2002;359:640-2.
    CrossRefMedlineWeb of Science
  5. ↵
    1. Desselberger U,
    2. Iturriza-Gomara M,
    3. Gray JJ
    . Rotavirus epidemiology and surveillance. Novartis Found Symp 2001;238:125-47. discussion, 147–52.
    MedlineWeb of Science
  6. ↵
    1. Palombo EA
    . Genetic and antigenic diversity of human rotaviruses: potential impact on the success of candidate vaccines. FEMS Microbiol Lett 1999;181:1-8.
    CrossRefMedlineWeb of Science
  7. ↵
    1. Howley PM
    1. Estes MK
    . Rotaviruses and their replication. In: Howley PM, editor. Fields virology. 4th ed. Vol. 2. Philadelphia: Lippincott, Williams & Wilkins; 2001. p. 1747-86.
    FREE Full Text
  8. ↵
    1. Offit PA
    . Rotaviruses: immunological determinants of protection against infection and disease. Adv Virus Res 1994;44:161-202.
    MedlineWeb of Science
  9. ↵
    1. Greenberg H,
    2. McAuliffe V,
    3. Valdesuso J,
    4. et al
    . Serological analysis of the subgroup protein of rotavirus using monoclonal antibodies. Infect Immun 1983;39:91-9.
    Abstract/FREE Full Text
  10. ↵
    1. Iturriza-Gomara M,
    2. Wong C,
    3. Blome S,
    4. Desselberger U,
    5. Gray J
    . Molecular characterization of VP6 genes of human rotavirus isolates: correlation of genogroups with subgroups and evidence of independent segregation. J Virol 2002;76:6596-601.
    Abstract/FREE Full Text
  11. ↵
    1. Matsui SM,
    2. Mackow ER,
    3. Matsuno S,
    4. Paul PS,
    5. Greenberg HB
    . Sequence analysis of gene 11 equivalents from “short” and “super short” strains of rotavirus. J Virol 1990;64:120-4.
    Abstract/FREE Full Text
  12. ↵
    1. Flores J,
    2. Perez I,
    3. White L,
    4. et al
    . Genetic relatedness among human rotaviruses as determined by RNA hybridization. Infect Immun 1982;37:648-55.
    Abstract/FREE Full Text
  13. ↵
    1. Nakagomi O,
    2. Nakagomi T,
    3. Akatani K,
    4. Ikegami N
    . Identification of rotavirus genogroups by RNA-RNA hybridization. Mol Cell Probes 1989;3:251-61.
    CrossRefMedlineWeb of Science
  14. ↵
    1. Wyatt RG,
    2. James HD Jr,
    3. Pittmann AL,
    4. et al
    . Direct isolation in cell culture of human rotaviruses and their characterization into four serotypes. J Clin Microbiol 1983;18:310-7.
    Abstract/FREE Full Text
  15. ↵
    1. Hoshino Y,
    2. Sereno MM,
    3. Midthun K,
    4. Flores J,
    5. Kapikian AZ,
    6. Chanock RM
    . Independent segregation of two antigenic specificities (VP3 and VP7) involved in neutralization of rotavirus infectivity. Proc Natl Acad Sci USA 1985;82:8701-4.
    Abstract/FREE Full Text
  16. ↵
    1. Offit PA,
    2. Blavat G
    . Identification of two rotavirus genes determining neutralization specificities. J Virol 1986;57:376-8.
    Abstract/FREE Full Text
  17. ↵
    1. Coulson B,
    2. Unicomb LE,
    3. Pitson GA,
    4. Bishop RF
    . Simple and specific enzyme immunoassay using monoclonal antibodies for serotyping human rotaviruses. J Clin Microbiol 1987;25:509-15.
    Abstract/FREE Full Text
  18. ↵
    1. Taniguchi K,
    2. Urasawa T,
    3. Morita Y,
    4. Greenberg HB,
    5. Urasawa S
    . Direct serotyping of human rotavirus in stools using serotype 1-, 2-, 3-, and 4-specific monoclonal antibodies to VP7. J Infect Dis 1987;155:1159-66.
    Abstract/FREE Full Text
  19. ↵
    1. Woods PA,
    2. Gentsch J,
    3. Gouvea V,
    4. et al
    . Distribution of serotypes of human rotavirus in different populations. J Clin Microbiol 1992;30:781-5.
    Abstract/FREE Full Text
  20. ↵
    1. Koshimura Y,
    2. Nakagomi T,
    3. Nakagomi O
    . The relative frequencies of G serotypes of rotaviruses recovered from hospitalized children with diarrhea: a 10-year survey (1987–1996) in Japan with a review of globally collected data. Microbiol Immunol 2000;44:499-510.
    MedlineWeb of Science
  21. ↵
    1. Coulson BS
    . VP4 and VP7 typing using monoclonal antibodies. Arch Virol Suppl 1996;12:113-8.
    Medline
  22. ↵
    1. Matsuno S,
    2. Hasegawa A,
    3. Mukoyama A,
    4. Inouye S
    . A candidate for a new serotype of human rotavirus. J Virol 1985;54:623-4.
    Abstract/FREE Full Text
  23. ↵
    1. Clark HF,
    2. Hoshino Y,
    3. Bell LM,
    4. et al
    . Rotavirus isolate W161 representing a presumptive new human serotype. J Clin Microbiol 1987;25:1757-62.
    Abstract/FREE Full Text
    1. Taniguchi K,
    2. Urasawa T,
    3. Kobayashi N,
    4. Gorziglia M,
    5. Urasawa S
    . Nucleotide sequence of VP4 and VP7 genes of human rotaviruses with subgroup I specificity and long RNA pattern: implication for new G serotype specificity. J Virol 1990;64:5640-4.
    Abstract/FREE Full Text
  25. ↵
    1. Nakagomi T,
    2. Akatani K,
    3. Ikegami N,
    4. Katsushima N,
    5. Nakagomi O
    . Occurrence of changes in human rotavirus serotypes with concurrent changes in genomic RNA electropherotypes. J Clin Microbiol 1988;26:2586-92.
    Abstract/FREE Full Text
  26. ↵
    1. Gorziglia M,
    2. Green K,
    3. Nishikawa K,
    4. et al
    . Sequence of the fourth gene of human rotaviruses recovered from asymptomatic or symptomatic infections. J Virol 1988;62:2978-84.
    Abstract/FREE Full Text
  27. ↵
    1. Gorziglia M,
    2. Larralde G,
    3. Kapikian AZ,
    4. Chanock RM
    . Antigenic relationships among human rotaviruses as determined by outer capsid protein VP4. Proc Natl Acad Sci USA 1990;87:7155-9.
    Abstract/FREE Full Text
  28. ↵
    1. Offit PA,
    2. Blavat G,
    3. Greenberg HB,
    4. Clark HF
    . Molecular basis of rotavirus virulence: role of gene segment 4. J Virol 1986;57:46-9.
    Abstract/FREE Full Text
  29. ↵
    1. Coulson BS
    . Typing of human rotavirus VP4 by an enzyme immunoassay using monoclonal antibodies. J Clin Microbiol 1993;31:1-8.
    Abstract/FREE Full Text
  30. ↵
    1. Padilla-Noriega L,
    2. Werner-Eckert R,
    3. Mackow ER,
    4. et al
    . Serologic analysis of human rotavirus serotypes P1A and P2 by using monoclonal antibodies. J Clin Microbiol 1993;31:622-8.
    Abstract/FREE Full Text
  31. ↵
    1. Gouvea V,
    2. Glass RI,
    3. Woods P,
    4. et al
    . Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens. J Clin Microbiol 1990;28:276-82.
    Abstract/FREE Full Text
  32. ↵
    1. Gentsch JR,
    2. Glass RI,
    3. Woods P,
    4. et al
    . Identification of group A rotavirus gene 4 types by polymerase chain reaction. J Clin Microbiol 1992;30:1365-73.
    Abstract/FREE Full Text
  33. ↵
    1. Gunasena S,
    2. Nakagomi O,
    3. Isegawa Y,
    4. et al
    . Relative frequency of VP4 gene alleles among human rotaviruses recovered over a 10 year period (1982–1991) from Japanese children with diarrhea. J Clin Microbiol 1993;31:2195-7.
    Abstract/FREE Full Text
  34. ↵
    1. Flores J,
    2. Sears J,
    3. Perez Schael I,
    4. Lanata C,
    5. Kapikian AZ
    . Identification of human rotavirus serotype by hybridization to polymerase chain reaction-generated probes derived from a hyperdivergent region of the gene encoding outer capsid protein VP7. J Virol 1990;64:4021-4.
    Abstract/FREE Full Text
  35. ↵
    1. Larralde G,
    2. Flores J
    . Identification of gene 4 alleles among human rotaviruses by polymerase chain reaction-derived probes. Virology 1990;179:469-73.
    CrossRefMedlineWeb of Science
  36. ↵
    1. Gentsch JR,
    2. Woods PA,
    3. Ramachandran M,
    4. et al
    . Review of G and P typing results from a global collection of strains: implications for vaccine development. J Infect Dis 1996;174:S30-6.
    CrossRefMedlineWeb of Science
  37. ↵
    1. Landaeta ME,
    2. Dove W,
    3. Vinh H,
    4. et al
    . Characterization of rotaviruses causing diarrhoea in Vietnamese children. Ann Trop Med Parasitol 2003;97:53-9.
    CrossRefMedlineWeb of Science
  38. ↵
    1. Ehlken B,
    2. Laubereau B,
    3. Karmaus W,
    4. et al
    . Prospective population-based study on rotavirus disease in Germany. Acta Paediatrica 2002;91:769-75.
    CrossRefMedlineWeb of Science
  39. ↵
    1. Buesa J,
    2. de Souza CO,
    3. Asensi M,
    4. Martinez C,
    5. Prat J,
    6. Gil MT
    . VP7 and VP4 genotypes among rotavirus strains recovered from children with gastroenteritis over a 3-year period in Valencia, Spain. Eur J Epidemiol 2000;16:501-6.
    CrossRefMedlineWeb of Science
  40. ↵
    1. Leite JP,
    2. Alfieri AA,
    3. Woods P,
    4. Glass RI,
    5. Gentsch JR
    . Rotavirus G and P types circulating in Brazil: characterization by RT-PCR, probe hybridization, and sequence analysis. Arch Virol 1996;141:2365-74.
    CrossRefMedlineWeb of Science
  41. ↵
    1. Ramachandran M,
    2. Das BK,
    3. Vij A,
    4. et al
    . Unusual diversity of human rotavirus G and P genotypes in India. J Clin Microbiol 1996;34:436-9.
    Abstract/FREE Full Text
  42. ↵
    1. Das BK,
    2. Kumar RK,
    3. Bhan MK
    . Rotavirus gastroenteritis and vaccine development. Indian J Pediatr 1998;65:S36-40.
  43. ↵
    1. Husain M,
    2. Seth P,
    3. Dar L,
    4. Broor S
    . Classification of rotavirus into G and P types with specimens from children with acute diarrhea in New Delhi, India. J Clin Microbiol 1996;34:1592-4.
    Abstract/FREE Full Text
  44. ↵
    1. O'Ryan M,
    2. Mamani N,
    3. Avendano LF,
    4. et al
    . Molecular epidemiology of human rotaviruses in Santiago, Chile. Pediatr Infect Dis J 1997;16:305-11.
    CrossRefMedlineWeb of Science
  45. ↵
    1. Arista S,
    2. Vizzi E,
    3. Ferraro D,
    4. Cascio A,
    5. Di Stefano R
    . Distribution of VP7 serotypes and VP4 genotypes among rotavirus strains recovered from Italian children with diarrhea. Arch Virol 1997;142:2065-71.
    CrossRefMedlineWeb of Science
    1. Adah MI,
    2. Rohwedder A,
    3. Olaleye OD,
    4. Durojaiye OA,
    5. Werchau H
    . Further characterization of field strains of rotavirus from Nigeria: VP4 genotype P6 most frequently identified among symptomatically infected children. J Trop Pediatr 1997;43:267-74.
    Abstract/FREE Full Text
    1. Ramachandran M,
    2. Gentsch JR,
    3. Parashar UD,
    4. et al
    . Detection and characterization of novel rotavirus strains in the United States. J Clin Microbiol 1998;36:3223-9.
    Abstract/FREE Full Text
    1. Griffin DD,
    2. Kirkwood C,
    3. Parashar UD,
    4. et al
    . Surveillance of rotavirus strains in the United States: identification of unusual strains. J Clin Microbiol 2000;38:2784-7.
    Abstract/FREE Full Text
  49. ↵
    1. Mascarenhas JDP,
    2. Paiva FL,
    3. Barardi CRM,
    4. Gabbay YB,
    5. Simoes CO,
    6. Linhares AC
    . Rotavirus G and P types in children in Belem, Northern Brazil, as determined by RT-PCR: occurrence of mixed P type infections. J Diarrhoeal Dis Res 1998;16:8-14.
    MedlineWeb of Science
  50. ↵
    1. Wu H,
    2. Taniguchi K,
    3. Urasawa T,
    4. Urasawa S
    . Serological and genomic characterization of human rotaviruses detected in China. J Med Virol 1998;55:168-76.
    CrossRefMedlineWeb of Science
  51. ↵
    1. Unicomb LE,
    2. Podder G,
    3. Gentsch JR,
    4. et al
    . Evidence of high-frequency genomic reassortment of group A rotavirus strains in Bangladesh: emergence of type G9 in 1995. J Clin Microbiol 1999;37:1885-91.
    Abstract/FREE Full Text
  52. ↵
    1. Iturriza-Gomara M,
    2. Green J,
    3. Brown DWG,
    4. Desselberger U,
    5. Gray JJ
    . Comparison of specific and random priming in the reverse transcription polymerase chain reaction for genotyping group A rotaviruses. J Virol Methods 1999;78:93-103.
    CrossRefMedlineWeb of Science
  53. ↵
    1. Cunliffe NA,
    2. Gondwe JS,
    3. Broadhead RL,
    4. et al
    . Rotavirus G and P types in children with acute diarrhea in Blantyre, Malawi, from 1997 to 1998: predominance of novel P[6]G8 strains. J Med Virol 1999;57:308-12.
    CrossRefMedlineWeb of Science
  54. ↵
    1. O'Mahony J,
    2. Foley B,
    3. Morgan S,
    4. Morgan JG,
    5. Hill C
    . VP4 and VP7 genotyping of rotavirus samples recovered from infected children in Ireland over a 3-year period. J Clin Microbiol 1999;37:1699-1703.
    Abstract/FREE Full Text
  55. ↵
    1. Rodriguez Castillo A,
    2. Villa AV,
    3. Ramirez Gonzalez JE,
    4. et al
    . VP4 and VP7 genotyping by reverse transcription-PCR of human rotavirus in Mexican children with acute diarrhea. J Clin Microbiol 2000;38:3876-8.
    Abstract/FREE Full Text
  56. ↵
    1. Espul C,
    2. Cuello H,
    3. Martinez N,
    4. et al
    . Genomic and antigenic variation among rotavirus strains circulating in a large city of Argentina. J Med Virol 2000;61:504-9.
    CrossRefMedlineWeb of Science
  57. ↵
    1. Bon F,
    2. Fromantin C,
    3. Aho S,
    4. Pothier P,
    5. Kohli E
    . G and P genotyping of rotavirus strains circulating in France over a three year period: detection of G9 and P[6] strains at low frequencies. J Clin Microbiol 2000;38:1681-3.
    Abstract/FREE Full Text
    1. Cubitt WD,
    2. Steele AD,
    3. Iturriza M
    . Characterisation of rotaviruses from children treated at a London hospital during 1996: emergence of strains G9P2A[6] and G3P2A[6]. J Med Virol 2000;61:150-4.
    CrossRefMedlineWeb of Science
  59. ↵
    1. Trabelsi A,
    2. Peenze I,
    3. Pager C,
    4. Jeddi M,
    5. Steele D
    . Distribution of rotavirus VP7 serotypes and VP4 genotypes circulating in Sousse, Tunisia, from 1995 to 1999: emergence of natural human reassortants. J Clin Microbiol 2000;38:3415-9.
    Abstract/FREE Full Text
    1. Audu R,
    2. Omilabu SA,
    3. de Beer M,
    4. Peenze I,
    5. Steele AD
    . Diversity of human rotavirus VP6, VP7, and VP4 in Lagos State, Nigeria. J Health Popul Nutr 2002;20:59-64.
    MedlineWeb of Science
  61. ↵
    1. Arguelles MH,
    2. Villegas GA,
    3. Castello A,
    4. et al
    . VP7 and VP4 genotyping of human group A rotavirus in Buenos Aires, Argentina. J Clin Microbiol 2000;38:252-9.
    Abstract/FREE Full Text
  62. ↵
    1. Araujo IT,
    2. Ferreira MSR,
    3. Failho AM,
    4. et al
    . Rotavirus genotypes P[4]G9, P[6]G9, and P[8]G9 in hospitalized children with acute gastroenteritis in Rio de Janeiro, Brazil. J Clin Microbiol 2001;39:1999-2001.
    Abstract/FREE Full Text
  63. ↵
    1. Fischer TK,
    2. Steinsland H,
    3. Molbak K,
    4. et al
    . Genotype profile of rotavirus strains from children in a suburban community in Guinea-Bissau, West Africa. J Clin Microbiol 2000;38:264-7.
    Abstract/FREE Full Text
  64. ↵
    1. Jain V,
    2. Das BK,
    3. Bhan MK,
    4. Glass RI,
    5. Gentsch JR
    . Great diversity of group A rotavirus strains and high prevalence of mixed rotavirus infections in India. Indian Strain Surveillance Collaborating Laboratories. J Clin Microbiol 2001;39:3524-9.
    Abstract/FREE Full Text
  65. ↵
    1. Bok K,
    2. Castagnaro N,
    3. Borsa A,
    4. et al
    . Surveillance for rotavirus in Argentina. J Med Virol 2001;65:190-8.
    CrossRefMedlineWeb of Science
    1. Ananthan S,
    2. Saravanan P
    . Genomic diversity of group A rotavirus RNA from children with acute diarrhoea in Chennai, south India. Indian J Med Res 2000;111:50-6.
    MedlineWeb of Science
  67. ↵
    1. Van Man N,
    2. Van Trang N,
    3. Lien HP,
    4. et al
    . The epidemiology and disease burden of rotavirus in Vietnam: sentinel surveillance at 6 hospitals. J Infect Dis 2001;183:1707-12.
    Abstract/FREE Full Text
  68. ↵
    1. O'Halloran F,
    2. Lynch M,
    3. Cryan B,
    4. O'Shea H,
    5. Fanning S
    . Molecular characterization of rotavirus in Ireland: detection of novel strains circulating in the population. J Clin Microbiol 2000;38:3370-4.
    Abstract/FREE Full Text
  69. ↵
    1. Asmah RH,
    2. Green J,
    3. Armah GE,
    4. et al
    . Rotavirus G and P genotypes in rural Ghana. J Clin Microbiol 2001;39:1981-4.
    Abstract/FREE Full Text
    1. Armah GE,
    2. Pager CT,
    3. Asmah RH,
    4. et al
    . Prevalence of unusual human rotavirus strains in Ghanaian children. J Med Virol 2001;63:67-71.
    CrossRefMedlineWeb of Science
  71. ↵
    1. Adah MI,
    2. Wade A,
    3. Taniguchi K
    . Molecular epidemiology of rotaviruses in Nigeria: detection of unusual strains with G2P[6] and G8P[1] specificities. J Clin Microbiol 2001;39:3969-75.
    Abstract/FREE Full Text
  72. ↵
    1. Coluchi N,
    2. Munford V,
    3. Manzur J,
    4. et al
    . Detection, subgroup specificity, and genotype diversity of rotavirus strains in children with acute diarrhea in Paraguay. J Clin Microbiol 2002;40:1709-14.
    Abstract/FREE Full Text
  73. ↵
    1. Steele AD,
    2. Kasolo FC,
    3. Bos P,
    4. Peenze I,
    5. Oshitani H,
    6. Mpabalwani E
    . Characterization of VP6 subgroup, VP7 and VP4 genotype of rotavirus strains in Lusaka, Zambia. Ann Trop Paediatr 1998;18:111-6.
    MedlineWeb of Science
  74. ↵
    1. Adhikary AK,
    2. Zhou Y,
    3. Kakizawa J,
    4. et al
    . Distribution of rotavirus VP4 genotype and VP7 serotype among Chinese children. Acta Paediatr Jpn 1998;40:641-3.
    Medline
  75. ↵
    1. Kang G,
    2. Green J,
    3. Gallimore CI,
    4. Brown DW
    . Molecular epidemiology of rotaviral infection in South Indian children with acute diarrhea from 1995–1996 to 1998–1999. J Med Virol 2002;67:101-5.
    CrossRefMedlineWeb of Science
  76. ↵
    1. Araujo IT,
    2. Fialho AM,
    3. de Assis RM,
    4. et al
    . Rotavirus strain diversity in Rio de Janeiro, Brazil: characterization of VP4 and VP7 genotypes in hospitalized children. J Trop Pediatr 2002;48:214-8.
    Abstract/FREE Full Text
  77. ↵
    1. Santos N,
    2. Soares CC,
    3. Volotao EM,
    4. Albuquerque MC,
    5. Hoshino Y
    . Surveillance of rotavirus strains in Rio de Janeiro, Brazil, from 1997 to 1999. J Clin Microbiol 2003;41:3399-402.
    Abstract/FREE Full Text
  78. ↵
    1. Rosa ESML,
    2. Pires De Carvalho I,
    3. Gouvea V
    . 1998–1999 Rotavirus seasons in Juiz de Fora, Minas Gerais, Brazil: detection of an unusual G3P[4] epidemic strain. J Clin Microbiol 2002;40:2837-42.
    Abstract/FREE Full Text
  79. ↵
    1. Kang G,
    2. Raman T,
    3. Green J,
    4. Gallimore CI,
    5. Brown DW
    . Distribution of rotavirus G and P types in north and south Indian children with acute diarrhoea in 1998–99. Trans R Soc Trop Med Hyg 2001;95:491-2.
    CrossRefMedlineWeb of Science
  80. ↵
    1. Das S,
    2. Sen A,
    3. Uma G,
    4. et al
    . Genomic diversity of group A rotavirus strains infecting humans in eastern India. J Clin Microbiol 2002;40:146-9.
    Abstract/FREE Full Text
  81. ↵
    1. Binka FN,
    2. Anto FK,
    3. Oduro AR,
    4. et al
    . Incidence and risk factors of paediatric rotavirus diarrhoea in northern Ghana. Trop Med Int Health 2003;8:840-6.
    CrossRefMedlineWeb of Science
  82. ↵
    1. Song MO,
    2. Kim KJ,
    3. Chung SI,
    4. et al
    . Distribution of human group A rotavirus VP7 and VP4 types circulating in Seoul, Korea between 1998 and 2000. J Med Virol 2003;70:324-8.
    CrossRefMedlineWeb of Science
  83. ↵
    1. Doan LT,
    2. Okitsu S,
    3. Nishio O,
    4. Pham DT,
    5. Nguyen DH,
    6. Ushijima H
    . Epidemiological features of rotavirus infection among hospitalized children with gastroenteritis in Ho Chi Minh City, Vietnam. J Med Virol 2003;69:588-94.
    CrossRefMedlineWeb of Science
  84. ↵
    1. Cunliffe N,
    2. Dove W,
    3. Bunn J,
    4. et al
    . Expanding global distribution of rotavirus serotype G9: detection in Libya, Kenya, and Cuba. Emerg Infect Dis 2001;7:890-2.
    MedlineWeb of Science
  85. ↵
    1. Abdel-Haq NM,
    2. Thomas RA,
    3. Asmar BI,
    4. Zacharova V,
    5. Lyman WD
    . Increased prevalence of G1P[4] genotype among children with rotavirus-associated gastroenteritis in metropolitan Detroit. J Clin Microbiol 2003;41:2680-2.
    Abstract/FREE Full Text
  86. ↵
    1. Souza MB,
    2. Racz ML,
    3. Leite JP,
    4. et al
    . Molecular and serological characterization of group A rotavirus isolates obtained from hospitalized children in Goiania, Brazil, 1998–2000. Eur J Clin Microbiol Infect Dis 2003;22:441-3.
    CrossRefMedlineWeb of Science
    1. Noppornpanth S,
    2. Theamboonlers A,
    3. Poovorawan Y
    . Predominant human rotavirus genotype G1P[8] infection in infants and children in Bangkok, Thailand. Asian Pac J Allergy Immunol 2001;19:49-53.
    MedlineWeb of Science
  88. ↵
    1. Mascarenhas JD,
    2. Linhares AC,
    3. Gabbay YB,
    4. Leite JP
    . Detection and characterization of rotavirus G and P types from children participating in a rotavirus vaccine trial in Belem, Brazil. Mem Inst Oswaldo Cruz 2002;97:113-7.
    MedlineWeb of Science
  89. ↵
    1. Bishop RF,
    2. Masendycz PJ,
    3. Bugg HC,
    4. Carlin JB,
    5. Barnes GL
    . Epidemiological patterns of rotaviruses causing severe gastroenteritis in young children throughout Australia from 1993 to 1996. J Clin Microbiol 2001;39:1085-91.
    Abstract/FREE Full Text
  90. ↵
    1. Iturriza-Gomara M,
    2. Green J,
    3. Brown D,
    4. Tamsay M,
    5. Desselberger U,
    6. Gray J
    . Molecular epidemiology of human group A rotavirus infections in the United Kingdom between 1995 and 1998. J Clin Microbiol 2000;38:4394-401.
    Abstract/FREE Full Text
  91. ↵
    1. Fruhwirth M,
    2. Brosl S,
    3. Ellemunter H,
    4. Moll-Schuler I,
    5. Rohwedder A,
    6. Mutz I
    . Distribution of rotavirus VP4 genotypes and VP7 serotypes among nonhospitalized and hospitalized patients with gastroenteritis and patients with nosocomially acquired gastroenteritis in Austria. J Clin Microbiol 2000;38:1804-6.
    Abstract/FREE Full Text
  92. ↵
    1. Banyai K,
    2. Gentsch J,
    3. Glass R,
    4. Uj M,
    5. Mihaly I,
    6. Szucs G
    . Eight-year survey of human rotavirus strains demonstrates circulation of unusual G and P types in Hungary. J Clin Microbiol 2004;42:393-7.
    Abstract/FREE Full Text
  93. ↵
    1. Fang Z-Y,
    2. Hui Y,
    3. Qi J,
    4. et al
    . Diversity of rotavirus strains among children with acute diarrhea in China: 1998–2000 surveillance study. J Clin Microbiol 2002;40:1875-8.
    Abstract/FREE Full Text
  94. ↵
    1. Laird AR,
    2. Ibarra V,
    3. Ruiz-Palacios G,
    4. Guerrero ML,
    5. Glass RI,
    6. Gentsch JR
    . Unexpected detection of animal VP7 genes among common rotavirus strains isolated from children in Mexico. J Clin Microbiol 2003;41:4400-3.
    Abstract/FREE Full Text
  95. ↵
    1. Cunliffe N,
    2. Gondwe JS,
    3. Graham SM,
    4. et al
    . Rotavirus strain diversity in Blantyre, Malawi from 1997 to 1999. J Clin Microbiol 2001;39:836-43.
    Abstract/FREE Full Text
    1. Martella V,
    2. Terio V,
    3. Del Gaudio G,
    4. et al
    . Detection of the emerging rotavirus G9 serotype at high frequency in Italy. J Clin Microbiol 2003;41:3960-3.
    Abstract/FREE Full Text
  97. ↵
    1. Rasool NBG,
    2. Larralde G,
    3. Gorziglia MI
    . Determination of human rotavirus VP4 using serotype-specific cDNA probes. Arch Virol 1993;133:275-82.
    CrossRefMedlineWeb of Science
    1. Kaga E,
    2. Iizuka M,
    3. Nakagomi T,
    4. Nakagomi O
    . The distribution of G (VP7) and P (VP4) serotypes among human rotaviruses recovered from Japanese children with diarrhea. Microbiol Immunol 1994;38:317-30.
    MedlineWeb of Science
  99. ↵
    1. Timenetsky Mdo C,
    2. Santos N,
    3. Gouvea V
    . Survey of rotavirus G and P types associated with human gastroenteritis in Sao Paulo, Brazil, from 1986 to 1992. J Clin Microbiol 1994;32:2622-4.
    Abstract/FREE Full Text
    1. Fang Z-Y,
    2. Shangjin J,
    3. Shuming Q,
    4. et al
    . Serotypes of group A rotavirus isolates determined by PCR in Hebei and Henan provinces, China. Chinese J Virol 1994;10:316-20.
  101. ↵
    1. Ushijima H,
    2. Mukoyama A,
    3. Hasegawa A,
    4. Nishimura S,
    5. Konishi K,
    6. Bosu K
    . Serotyping of human rotaviruses in the Tokyo area (1990–1993) by enzyme immunoassay with monoclonal antibodies and by reverse transcription and polymerase chain reaction amplification. J Med Virol 1994;44:162-5.
    MedlineWeb of Science
    1. Wu H,
    2. Taniguchi K,
    3. Wakasugi F,
    4. et al
    . Survey on the distribution of the gene 4 alleles of human rotaviruses by polymerase chain reaction. Epidemiol Infect 1994;112:615-22.
    Medline
  103. ↵
    1. Santos N,
    2. Riepenhoff-Talty M,
    3. Clark HF,
    4. Offit P,
    5. Gouvea V
    . VP4 genotyping of human rotavirus in the United States. J Clin Microbiol 1994;32:205-8.
    Abstract/FREE Full Text
    1. Silberstein I,
    2. Shulman LM,
    3. Mendelson E,
    4. Shif I
    . Distribution of both rotavirus VP4 genotypes and VP7 serotypes among hospitalized and nonhospitalized Israeli children. J Clin Microbiol 1995;33:1421-2.
    Abstract/FREE Full Text
  105. ↵
    1. Steele AD,
    2. van Niekerk MC,
    3. Mphahlele MJ
    . Geographic distribution of human rotavirus VP4 genotypes and VP7 serotypes in five South African regions. J Clin Microbiol 1995;33:1516-9.
    Abstract/FREE Full Text
  106. ↵
    1. Gouvea V,
    2. de Castro L,
    3. Timenetsky Mdo C,
    4. Greenberg H,
    5. Santos N
    . Rotavirus serotype G5 associated with diarrhea in Brazilian children. J Clin Microbiol 1994;32:1408-9. [erratum:J Clin Microbiol 1994;32:1834].
    Abstract/FREE Full Text
  107. ↵
    1. Steele AD,
    2. Ivanoff B
    . Rotavirus strains circulating in Africa during 1996–1999: emergence of G9 strains and P[6] strains. Vaccine 2003;21:361-7.
    CrossRefMedlineWeb of Science
  108. ↵
    1. Laird AR,
    2. Gentsch JR,
    3. Nakagomi T,
    4. Nakagomi O,
    5. Glass RI
    . Characterization of serotype G9 rotavirus strains isolated in the United States and India from 1993 to 2001. J Clin Microbiol 2003;41:3100-11.
    Abstract/FREE Full Text
  109. ↵
    1. Kirkwood C,
    2. Bogdanovic-Sakran N,
    3. Clark R,
    4. Masendycz P,
    5. Bishop R,
    6. Barnes G
    . Report of the Australian Rotavirus Surveillance Program, 2001/2002. Commun Dis Intell 2002;26:537-40.
    Medline
  110. ↵
    1. Kirkwood C,
    2. Bogdanovic-Sakran N,
    3. Palombo E,
    4. et al
    . Genetic and antigenic characterization of rotavirus serotype G9 strains isolated in Australia between 1997 and 2001. J Clin Microbiol 2003;41:3649-54.
    Abstract/FREE Full Text
  111. ↵
    1. Cunliffe NA,
    2. Gentsch JR,
    3. Kirkwood CD,
    4. et al
    . Molecular and serologic characterization of novel serotype G8 rotavirus strains detected in Blantyre, Malawi. Virology 2000;274:309-20.
    CrossRefMedlineWeb of Science
    1. Timenetsky Mdo C,
    2. Gouvea V,
    3. Santos N,
    4. Carmona RC,
    5. Hoshino Y
    . A novel human rotavirus serotype with dual G5–G11 specificity. J Gen Virol 1997;78:1373-8.
    Abstract/FREE Full Text
  113. ↵
    1. Griffin DD,
    2. Nakagomi T,
    3. Hoshino Y,
    4. et al
    . Characterization of nontypeable rotavirus strains from the United States: identification of a new rotavirus reassortant (P2A[6],G12) and rare P3[9] strains related to bovine rotaviruses. Virology 2002;294:256-69.
    CrossRefMedlineWeb of Science
    1. Nakagomi T,
    2. Horie Y,
    3. Koshimura Y,
    4. Greenberg HB,
    5. Nakagomi O
    . Isolation of human rotavirus with a super-short RNA pattern possessing a new P2 subtype. J Clin Microbiol 1999;37:1213-6.
    Abstract/FREE Full Text
    1. Isegawa Y,
    2. Nakagomi O,
    3. Nakagomi T,
    4. Ueda S
    . A VP4 sequence highly conserved in human rotavirus strain AU-1 and feline rotavirus strain FRV-1. J Gen Virol 1992;73:1939-46.
    Abstract/FREE Full Text
    1. Gerna G,
    2. Sarasini A,
    3. Parea M,
    4. et al
    . Isolation and characterization of two distinct human rotavirus strains with G6 specificity. J Clin Microbiol 1992;30:9-16.
    Abstract/FREE Full Text
    1. Pongsuwanna Y,
    2. Guntapong R,
    3. Chiwakul M,
    4. et al
    . Detection of a human rotavirus with G12 and P[9] specificity in Thailand. J Clin Microbiol 2002;40:1390-4.
    Abstract/FREE Full Text
    1. Taniguchi K,
    2. Nishikawa K,
    3. Urasawa T,
    4. et al
    . Complete nucleotide sequence of the gene encoding VP4 of a human rotavirus (strain K8) which has unique VP4 neutralization epitopes. J Virol 1989;63:4101-6.
    Abstract/FREE Full Text
    1. Qian Y,
    2. Green KY
    . Human rotavirus strain 69M has a unique VP4 as determined by amino acid sequence analysis. Virology 1991;182:407-12.
    CrossRefMedlineWeb of Science
    1. Li B,
    2. Clark HF,
    3. Gouvea V
    . Nucleotide sequence of the VP4-encoding gene of an unusual human rotavirus (HCR3). Virology 1993;196:825-30.
    CrossRefMedlineWeb of Science
  121. ↵
    1. Gentsch J,
    2. Das BK,
    3. Jiang B,
    4. Bhan MK,
    5. Glass RI
    . Similarity of the VP4 protein of human rotavirus strain 116E to that of the bovine B223 strain. Virology 1993;194:424-30.
    CrossRefMedlineWeb of Science
    1. Das M,
    2. Dunn SJ,
    3. Woode GN,
    4. Greenberg HB,
    5. Rao CD
    . Both surface proteins (VP4 and VP7) of an asymptomatic neonatal rotavirus strain (I321) have high levels of sequence identity with the homologous proteins of a serotype 10 bovine rotavirus. Virology 1993;194:374-9.
    CrossRefMedlineWeb of Science
    1. Gerna G,
    2. Sears J,
    3. Hoshino Y,
    4. et al
    . Identification of a new VP4 serotype of human rotavirus. Virology 1994;200:66-71.
    CrossRefMedline
    1. Palombo EA,
    2. Bishop RF
    . Genetic and antigenic characterization of a serotype G6 human rotavirus isolated in Melbourne, Australia. J Med Virol 1995;47:348-54.
    MedlineWeb of Science
  125. ↵
    1. Browning GF,
    2. Snodgrass DR,
    3. Nakagomi O,
    4. Kaga E,
    5. Sarasini A,
    6. Gerna G
    . Human and bovine serotype G8 rotaviruses may be derived by reassortment. Arch Virol 1992;125:121-8.
    CrossRefMedlineWeb of Science
  126. ↵
    1. Iizuka M,
    2. Kaga E,
    3. Chiba M,
    4. Masamune O,
    5. Gerna G,
    6. Nalagomi O
    . Serotype G6 human rotavirus sharing a conserved genetic constellation with natural reassortants between members of the bovine and AU-1 genogroups. Arch Virol 1994;135:427-32.
    CrossRefMedlineWeb of Science
    1. Urasawa T,
    2. Taniguchi K,
    3. Kobayashi N,
    4. et al
    . Nucleotide sequence of VP4 and VP7 genes of a unique human rotavirus strain Mc35 with subgroup I and serotype 10 specificity. Virology 1993;195:766-71.
    CrossRefMedline
    1. Okada J-I,
    2. Urasawa T,
    3. Kobayashi N,
    4. et al
    . New P serotype of a human rotavirus closely related to that of a porcine rotavirus. J Med Virol 2000;60:63-9.
    CrossRefMedlineWeb of Science
  129. ↵
    1. Rahman M,
    2. De Leener K,
    3. Goegebuer T,
    4. et al
    . Genetic characterization of a novel, naturally occurring recombinant human G6P[6] rotavirus. J Clin Microbiol 2003;41:2088-95.
    Abstract/FREE Full Text
  130. ↵
    1. Nakagomi T,
    2. Nakagomi O
    . Human rotavirus HCR3 possesses a genomic RNA constellation indistinguishable from that of feline and canine rotaviruses. Arch Virol 2000;145:2403-9.
    CrossRefMedlineWeb of Science
  131. ↵
    1. Nakagomi T,
    2. Nakagomi O
    . RNA-RNA hybridization identifies a human rotavirus that is genetically related to feline rotavirus. J Virol 1989;63:1431-4.
    Abstract/FREE Full Text
  132. ↵
    1. Gouvea V,
    2. Brantly M
    . Is rotavirus a population of reassortants? Trends Microbiol 1995;3:159-62.
    CrossRefMedline
  133. ↵
    1. Bernstein DI,
    2. Sack DA,
    3. Rothstein E,
    4. et al
    . Efficacy of live, attenuated, human rotavirus vaccine 89-12 in infants: a randomised placebo-controlled trial. Lancet 1999;354:287-90.
    CrossRefMedlineWeb of Science
  134. ↵
    1. Clark HF,
    2. Offit PA,
    3. Ellis RW,
    4. et al
    . The development of multivalent bovine rotavirus (strain WC3) reassortant vaccine for infants. J Infect Dis 1996;174 Suppl 1:S73-80.
    CrossRefMedlineWeb of Science
  135. ↵
    1. Perez-Schael I,
    2. Salinas B,
    3. Linhares AC,
    4. et al
    . Program and abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy (San Diego). Washington, DC: American Society for Microbiology; 2002. Protective efficacy of an oral human rotavirus (HRV) vaccine in Latin American infants [abstract 02-LB-3961].
  136. ↵
    1. Ramig R,
    2. Ward R
    . Genomic segment reassortment in rotaviruses and other Reoviridae. Adv Virus Res 1991;39:163-207.
    MedlineWeb of Science
  137. ↵
    1. Suzuki Y,
    2. Gojobori T,
    3. Nakagomi O
    . Intragenic recombinations in rotaviruses. FEBS Lett 1998;427:183-7.
    CrossRefMedlineWeb of Science
  138. ↵
    1. Maunula L,
    2. von Bonsdorff C-H
    . Short sequences define genetic lineages: phylogenetic analysis of group A rotaviruses based on partial sequences of genome segments 4 and 9. J Gen Virol 1998;79:321-32.
    Abstract/FREE Full Text
  139. ↵
    1. Iturriza-Gomara M,
    2. Isherwood B,
    3. Desselberger U,
    4. Gray J
    . Reassortment in vivo: driving force for diversity of human rotavirus strains isolated in the United Kingdom between 1995 and 1999. J Virol 2001;75:3696-705.
    Abstract/FREE Full Text
  140. ↵
    1. Maunula L,
    2. Von Bonsdorff CH
    . Frequent reassortments may explain the genetic heterogeneity of rotaviruses: analysis of Finnish rotavirus strains. J Virol 2002;76:11793-800.
    Abstract/FREE Full Text
  141. ↵
    1. Palombo EA,
    2. Bugg HC,
    3. Masendycz PJ,
    4. Coulson BS,
    5. Barnes GL,
    6. Bishop RF
    . Multiple-gene rotavirus reassortants responsible for an outbreak of gastroenteritis in central and northern Australia. J Gen Virol 1996;77:1223-7.
    Abstract/FREE Full Text
    1. Flores J,
    2. Perez-Schael I,
    3. Boeggeman E,
    4. et al
    . Genetic relatedness among human rotaviruses. J Med Virol 1985;17:135-43.
    CrossRefMedlineWeb of Science
    1. Nakagomi O,
    2. Nakagomi T
    . Molecular evidence for naturally occurring single VP7 gene substitution reassortant between human rotaviruses belonging to two different genogroups. Arch Virol 1991;119:67-81.
    CrossRefMedlineWeb of Science
  144. ↵
    1. Ward RL,
    2. Nakagomi O,
    3. Knowlton DR,
    4. et al
    . Evidence for natural reassortants of human rotaviruses belonging to different genogroups. J Virol 1990;64:3219-25.
    Abstract/FREE Full Text
  145. ↵
    1. Ramachandran M,
    2. Kirkwood CD,
    3. Unicomb L,
    4. et al
    . Molecular characterization of serotype G9 rotavirus strains from a global collection. Virology 2000;278:436-44.
    CrossRefMedlineWeb of Science
  146. ↵
    1. Iturriza-Gomara M,
    2. Cubitt D,
    3. Steele D,
    4. et al
    . Characterisation of rotavirus G9 strains isolated in the UK between 1995 and 1998. J Med Virol 2000;61:510-7.
    CrossRefMedlineWeb of Science
    1. Oka T,
    2. Nakagomi T,
    3. Nakagomi O
    . Apparent re-emergence of serotype G9 in 1995 among rotaviruses recovered from Japanese children hospitalized with acute gastroenteritis. Microbiol Immunol 2000;44:957-61.
    MedlineWeb of Science
    1. Bok K,
    2. Palacios G,
    3. Sijvarger K,
    4. Matson D,
    5. Gomez J
    . Emergence of G9 P[6] human rotaviruses in Argentina: phylogenetic relationships among G9 strains. J Clin Microbiol 2001;39:4020-5.
    Abstract/FREE Full Text
  149. ↵
    1. Santos N,
    2. Volotao EM,
    3. Soares CC,
    4. et al
    . Rotavirus strains bearing genotype G9 or P[9] recovered from Brazilian children with diarrhea from 1997 to 1999. J Clin Microbiol 2001;39:1157-60.
    Abstract/FREE Full Text
  150. ↵
    1. Santos N,
    2. Lima RC,
    3. Nozawa CM,
    4. Linhares RE,
    5. Gouvea V
    . Detection of porcine rotavirus type G9 and of a mixture of types G1 and G5 associated with Wa-like VP4 specificity: evidence for natural human-porcine genetic reassortment. J Clin Microbiol 1999;37:2734-6.
    Abstract/FREE Full Text
  151. ↵
    1. Das BK,
    2. Gentsch JR,
    3. Hoshino Y,
    4. et al
    . Characterization of the G serotype and genogroup of New Delhi newborn rotavirus strain 116E. Virology 1993;197:99-107.
    CrossRefMedlineWeb of Science
  152. ↵
    1. Dunn SJ,
    2. Greenberg HB,
    3. Ward RC,
    4. et al
    . Serotypic and genotypic characterization of human serotype 10 rotaviruses from asymptomatic neonates. J Clin Microbiol 1993;31:165-9.
    Abstract/FREE Full Text
  153. ↵
    1. Alfieri AA,
    2. Leite JPG,
    3. Nakagomi O,
    4. et al
    . Characterization of human rotavirus genotype P[8]G5 from Brazil by probe-hybridization and sequence. Arch Virol 1996;141:2353-64.
    CrossRefMedlineWeb of Science
  154. ↵
    1. Iizuka M,
    2. Kaga E,
    3. Chiba M,
    4. Masamune O,
    5. Gerna G,
    6. Nakagomi O
    . Serotype G6 human rotavirus sharing a conserved genetic constellation with natural reassortants between members of the bovine and AU-1 genogroups. Arch Virol 1994;135:427-32.
    CrossRefMedlineWeb of Science
  155. ↵
    1. Banyai K,
    2. Gentsch J,
    3. Griffin DD,
    4. Holmes JL,
    5. Glass RI,
    6. Szucs G
    . Genetic variability among serotype G6 human rotaviruses: identification of a novel lineage isolated in Hungary. J Med Virol 2003;71:124-34.
    CrossRefMedlineWeb of Science
  156. ↵
    1. Ohshima A,
    2. Takagi T,
    3. Nakagomi T,
    4. Matsuno S,
    5. Nakagomi O
    . Molecular characterization by RNA-RNA hybridization of a serotype 8 human rotavirus with “super-short” RNA electropherotype. J Med Virol 1990;30:107-12.
    MedlineWeb of Science
    1. Holmes JL,
    2. Kirkwood CD,
    3. Gerna G,
    4. et al
    . Characterization of unusual G8 rotavirus strains isolated from Egyptian children. Arch Virol 1999;144:1381-96.
    CrossRefMedlineWeb of Science
  158. ↵
    1. Palombo EZ,
    2. Clark R,
    3. Bishop RF
    . Characterisation of a “European-like” serotype G8 human rotavirus isolated in Australia. J Med Virol 2000;60:56-62.
    CrossRefMedlineWeb of Science
  159. ↵
    1. Ahmed MU,
    2. Urasawa S,
    3. Taniguchi K,
    4. et al
    . Analysis of human rotavirus strains prevailing in Bangladesh in relation to nationwide floods brought by the 1988 monsoon. J Clin Microbiol 1991;29:2273-9.
    Abstract/FREE Full Text
  160. ↵
    1. Fischer TK,
    2. Page NA,
    3. Griffin DD,
    4. et al
    . Characterization of incompletely typed rotavirus strains from Guinea-Bissau: identification of G8 and G9 types and a high frequency of mixed infections. Virology 2003;311:125-33.
    CrossRefMedline
  161. ↵
    1. Albert MJ,
    2. Unicomb LE,
    3. Barnes GL,
    4. Bishop RF
    . Cultivation and characterization of rotavirus strains infecting newborn babies in Melbourne, Australia from 1975 to 1979. J Clin Microbiol 1987;25:1635-40.
    Abstract/FREE Full Text
  162. ↵
    1. Cunliffe NA,
    2. Rogerson S,
    3. Dove W,
    4. et al
    . Detection and characterization of rotaviruses in hospitalized neonates in Blantyre, Malawi. J Clin Microbiol 2002;40:1534-7.
    Abstract/FREE Full Text
  163. ↵
    1. Bhan MK,
    2. Lew JF,
    3. Sazawal S,
    4. Das BK,
    5. Gentsch JR,
    6. Glass RI
    . Protection conferred by neonatal rotavirus infection against subsequent diarrhea. J Infect Dis 1993;168:282-7.
    Abstract/FREE Full Text
  164. ↵
    1. Sukumaran M,
    2. Gowda K,
    3. Maiya PP,
    4. et al
    . Exclusive asymptomatic neonatal infections by human rotavirus strains having subgroup I specificity and ‘long’ RNA electropherotype. Arch Virol 1992;126:239-51.
    CrossRefMedlineWeb of Science
  165. ↵
    1. Iturriza Gomara M,
    2. Kang G,
    3. Mammen A,
    4. et al
    . Characterization of G10P[11] rotaviruses causing acute gastroenteritis in neonates and infants in Vellore, India. J Clin Microbiol 2004;42:2541-7.
    Abstract/FREE Full Text
  166. ↵
    1. Santos N,
    2. Hoshino Y
    . Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev Med Virol 2005;15:29-56.
    CrossRefMedlineWeb of Science
| Table of Contents

This Article

  1. J Infect Dis. (2005) 192 (Supplement 1): S146-S159. doi: 10.1086/431499
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 205 (5)
  1. Journal of Infectious Diseases
  1. Alert me to new issues

Most