HK75 is also the oldest known Lineage I strain and the immediate precursor to all contemporary lineages. It is of interest that Lineage I G9 strains have been shown to exhibit the broadest neutralizing cross-reactivity, as they neutralize Lineage II and III G9 strains to high titer, making them ideal vaccine candidates [46]. Previous analyses of G5 rotaviruses suggested http://www.selleckchem.com/products/MDV3100.html that zoonotic or natural reassortment events may have given rise to G5 diversity [38]�C[40]. Our analysis confirmed the presence of three previously defined G5 lineages [39], each associated with at least one zoonotic event. All human strains clustered within two lineages (I and III), and both lineages also contained porcine strains, but no other types of animal strains, suggesting that swine may be involved with zoonotic transmission to humans.
Lineage II contained no human strains, but closely related animal strains (swine, cattle, and horses). Strain HK69 predates the oldest known human G5 strains from Brazil [38], which indicates that any natural reassortment or zoonotic event may have occurred as early as 1978. This study identified a variety of norovirus genotypes, and an evolutionary analysis of full-length norovirus VP1 genes illustrated this diversity. Norovirus genotypes from this cohort were diverse globally, indicating no evident trend in distribution. A previous evolutionary analysis of GII.3 noroviruses suggested that, although these viruses accumulate mutations over time, they tend to eventually revert back to the amino acid composition of older strains [47].
Our analysis supports this finding and suggests that other norovirus genotypes may exhibit similar characteristics (GI.3, GI.5, GI.6, GII.6, GII.7, and GII.17). Genotype GII.4 noroviruses are the most common strains associated with outbreaks of norovirus gastroenteritis worldwide [12], [14]�C[16], [43]. However, GII.4 noroviruses detected in this study (n=6) were outnumbered by GII.2 (n=10) and GI.3 (n=8) noroviruses, an observation that could reflect sampling procedures or the distribution of genotypes at that time. The original objective of this study was to document cases of viral associated diarrhea in specific settings globally, and not necessarily to characterize outbreaks. One of the six GII.4 norovirus strains detected in this collection (Hu/NoV/C127/FrenchGuiana/1978/GII.
4) had sufficient RNA quality for full-length VP1 capsid sequencing and phylogenetic analysis; this strain AV-951 clustered with the oldest GII.4 variants from Children��s Hospital, Washington DC (1974�C1977) [48]. However, two additional genogroup GII variants with closest homology to the GII.4 genotype (Hu/NoV/KL45/Malaysia/1978/GII.na and Hu/NoV/T091/Tunisia/1976/GII.na) were also detected in specimens collected in a similar time frame, but did not meet the criterion for belonging to GII.4 (>14.3% aa distance) [13].