Genetic Characterization of a Novel, Naturally Occurring Recombinant Human G6P[6] Rotavirus

Abstract

A binary classification system has been established for group A rotaviruses, with the viral capsid protein VP7 defining G types and VP4 defining P types. At least 15 G types and 21 P types have been isolated globally with various G and P combinations. Most of the currently circulating human rotaviruses belong to G1P[8], G2P[4], G3P[8], and G4P[8]. We report a human rotavirus strain (B1711) with a novel genotypic VP7/VP4 combination of G6P[6]. This unique rotavirus was isolated from a 13-month-old human immunodeficiency virus (HIV)-negative child of an HIV-seropositive Malian mother that was hospitalized with severe diarrhea in Belgium after returning from a trip to Mali. The VP7 and VP4 genes of the rotavirus strain were sequenced, and phylogenetic trees were constructed. Nucleotide and amino acid sequence comparisons with 15 known G genotypes indicated that the VP7 sequence of strain B1711 was most closely related to an American (Se584) and an Italian (PA151) human G6 strain (95 to 96% nucleotide and 98% amino acid identity). Comparison of the VP4 sequence with 21 P types showed the closest similarity to P[6] genotypes, with greatest similarity to a G8P[6] Malawi strain (mw131) (97% nucleotide and 98% amino acid identity). The B1711 strain is the first reported rotavirus isolate with a G6P[6] genotypic combination. The discovery and surveillance of novel human and nonhuman rotavirus G or P types or of novel G/P combinations is essential for the design of future rotavirus vaccines and for our understanding of rotavirus diversity and evolution.Group A rotaviruses are the single most important etiological agent associated with gastroenteritis in infants and young children (2, 40). Rotavirus-associated diarrhea leads to more than 125 million cases of infantile gastroenteritis and 870,000 deaths each year, primarily in less developed countries (54). In the United States it also results in $274 million in medical care costs and a total of $1 billion in societal costs (including indirect cost of lost parental work time) per year (47). Rotaviruses contain 11 segments of double-stranded RNA within a core shell and are members of the Reoviridae family. Each segment encodes a single viral polypeptide, for a total of five nonstructural and six structural proteins (17). The two outer capsid proteins VP7 and VP4, which independently elicit neutralizing antibodies, are the basis of a binary classification system for rotaviruses: G types (derived from the VP7 glycoprotein) and P types (derived from the protease sensitive VP4 protein). Thus far, 15 different G genotypes and 21 different P genotypes have been reported (2,26,31,48). Because VP4 and VP7 are encoded by different RNA segments, various combinations of G and P types can be observed (40). Most G genotypes were serologically confirmed as serotypes (25). Due to the lack of appropriate antibody reagents, a dual P-typing system (P serotype and P genotype) has been used (18). Strains sharing more than 89% sequence identity at the amino acid level are considered to belong to...

Severity of Diarrhea and Malnutrition among Under Five-Year-Old Children in Rural Bangladesh

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The Impact of Socio-Economic Conditions and Clinical Characteristics on Improving Childhood Care Seeking Behaviors for Families Living far from the Health Facility

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Sequencing and Phylogenetic Analysis of Human Genotype P[6] Rotavirus Strains Detected in Hungary Provides Evidence for Genetic Heterogeneity within the P[6] VP4 Gene

“…By extrapolation of the data collected from international reports, these six strains are responsible for more than 90 to 95% of all hospitalization cases, while the remaining 5 to 10% of cases are associated with unusual combinations of the common P and G types (e.g., P [4],G1; P [6],G3; or P [8],G2) and with rare strains, some of which seem to have primarily local relevance (e.g., P [9],G6 in Hungary or P [8],G5 in South America). Although epidemiological observations suggest the existence of genetic linkages between the most common human VP4 and VP7 specificities (genotype P [8] is in linkage with the G1, G3, G4, and G9 specificities, whereas genotype P [4] is associated mainly with the G2 specificity), in this regard the relatively prevalent human P type, P [6], may represent an exception based on data that it has been found to be in association with most of the human VP7 specificities (5,6,13,29).…”

“…Serotypes G6 and G8, identified frequently in ruminants, or serotype G5, common in pigs but rare in humans, exemplify this hypothesis (2,4,6,11). Although direct epidemiological evidence is still lacking, studies based on full genome hybridization and, more recently, on sequence and phylogenetic analysis seem to support the hypothesis that interspecies transmission may occur (4,13,29), even though such analyses usually cannot demonstrate direct evolutionary ancestry between recent animal and human strains. Indeed, gene sequences of animal strains segregate in most instances apart from those of human strains, suggesting either a strong diversification after the host switching or unequal distribution of distinct phylogenetic lineages in different hosts.…”