Molecular Characteristics of German G8P[4] Rotavirus Strain GER1H-09 Suggest that a Genotyping and Subclassification Update Is Required for G8

Abstract

A rare G8P[4] rotavirus, designated GER1H-09, was detected in a stool sample from an infant suffering from repeated episodes of emesis for 2 days without diarrhea. Sequencing of all genomic RNA segments was performed, and complete coding sequences were determined. The VP7 amino acid sequence revealed a close phylogenetic relationship to human G8P[6] and G8P [8] isolates from Slovenia and Africa. GER1H-09 shared typical amino acid residues within variable regions VR3 to VR7 with those strains, and their subclassification as lineage G8-II rotaviruses is proposed. The variability in VR3 was identified as the likely reason for the failure in genotyping G8-II rotaviruses by commonly used multiplex PCR. Furthermore, the sequences of associated structural and nonstructural proteins showed high amino acid identities to DS-1-like rotaviruses. The genotype composition of GER1H-09 (G8-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2) suggests the occurrence of reassortment events between G8 genotypes and human DS-1-like G2P[4] rotaviruses.Rotaviruses (RVs) are the main etiological agents of gastroenteritis worldwide. They occur in humans and animals, and the annual death rate is Ͼ600,000 children (26). Like other members of the family Reoviridae, the rotaviral genome consists of 11 double-stranded RNA segments enclosed by a triple-layered nucleocapsid. Seven RV groups (A to G) are determined by the antigenetic properties of the middle layer capsid protein (VP6) (7). RV infections in humans are mainly caused by group A RVs (18). They are further classified into different P and G genotypes based upon the main neutralization antigens, namely, the spike protein (VP4) and the major outer capsid glycoprotein (VP7) (7). The most prevalent genotypes, G1P [8] and G9P[8], are responsible for approximately 90% of worldwide human RV infections (30). RV epidemiology is in a constant state of diversification, mainly driven by frequent reassortment events (17). For discovery of reassortment events, genotyping of all genomic RNA segments, including the other structural proteins (VP1-3, VP6) and the nonstructural proteins (NSP1-5), is mandatory (22,23). With regard to the high incidence of RV infections worldwide, two oral live-attenuated vaccines have been licensed. Rotarix is a monovalent vaccine derived from a human G1P [8] strain that has been attenuated by serial passages (29). RotaTeq is a human-bovine reassortant RV vaccine and contains the human genotypes G1, G2, G3, G4, and P[8] (37). The postmarketing surveillance of circulating RV genotypes is crucial for vaccine efficacy studies. A close look at rotavirus genotypes in Germany has already revealed the circulation of uncommon human G10 and G12 rotaviruses in prior studies (19,28,35). Here we add to the already known diversity by the description of a recent G8 genotype variant derived from a stool sample from a German infant. The subclassification of G8 genotypes into lineages I and II is proposed. CASE REPORTAn 11-month-old girl was admitted to hospital (Department of Pediatrics, Hospital St. Eli...

Vaccine preventable viral diseases and risks associated with waterborne transmission

“…This process of "humanization" following zoonotic transmission may further proceed generating new virus reassortants, as was shown in two distinct G8P [8] and G8P [4] rotaviruses reported in 2006 and 2009 in Europe, showing partial or little similarity with the DRC strains and close phylogenetic links with other common human rotavirus circulating in Europe belonging to G types other than G8 [38,39]. One of these latter strains, G8P [8] with a full Wa-like genome, unexpectedly became predominant among children with severe gastroenteritis in Croatia in 2006, suggesting that its emergence was [36,38] favored by an unusual gene repertoire [13,17,36].…”

First Reports of Human Rotavirus G8P[4] Gastroenteritis in the United States

“…No other demographic or clinical differences among these children were found, although all were ill enough to be hospitalized (Table 1). None of the children had unusual travel, dietary, or animal contact; some G8 rotavirus strains infecting humans are thought to reflect a bovine origin (7,11,13,22,27). This suggests endemic circulation and transmission of the G8P [4] strains in the community, a hypothesis supported by the possible intrafamilial spread in two of the case patients.…”

“…Sequencing and phylogenetic analysis of partial VP7 and VP4 gene sequences from these 3 G8P [4] strains, designated US09Ro045, US09Ro103, and US09Ro104, revealed that all 3 exhibited 99 to 100% identity with the VP7 and VP4 genes of the 2009 German rotavirus strain GER1H-09 ( Fig. 1) and shared phylogenetic lineage with it (27). Full-genome sequencing of these 3 strains is under way (our unpublished data).…”

“…The emergence of G8P [4] strains, which are now being detected in the United States, in several locations in Europe (1,15,27) raises questions about the effectiveness of current rotavirus vaccines, which share neither G nor P types with G8P [4] viruses. Similar questions have been raised in the context of a greater prevalence of G2P [4] strains observed after routine implementation of the monovalent G1P [8] rotavirus vaccine in Brazil and in parts of Australia and Belgium (4,17,35).…”

Full-Genome Characterization of a G8P[8] Rotavirus That Emerged among Children with Diarrhea in Croatia in 2006

“…Bovine-like G8 rotavirus was first reported in an Indonesian child (12), and further G8 RVA human cases occurred worldwide, including in industrialized countries (13)(14)(15)(16)(17)(18)(19)(20)(21). Using full-genome sequencing, G8P [8] African RVAs were shown to involve reassortment between at least four human, swine, and bovine strains (22).…”