Distinguishing the genotype 1 genes and proteins of human Wa-like rotaviruses vs. porcine rotaviruses

Abstract

Group A rotaviruses (RVAs) are 11-segmented, double-stranded RNA viruses and important causes of gastroenteritis in the young of many animal species. Previous studies have suggested that human Wa-like RVAs share a close evolutionary relationship with porcine RVAs. Specifically, the VP1-VP3 and NSP2-5/6 genes of these viruses are usually classified as genotype 1 with >81% nucleotide sequence identity. Yet, it remains unknown whether the genotype 1 genes and proteins of human Wa-like strains are distinguishable from those of porcine strains. To investigate this, we performed comprehensive bioinformatic analyses using all known genotype 1 gene sequences. The RVAs analyzed represent wildtype strains isolated from humans or pigs at various geographical locations during the years of 2004–2013, including 11 newly-sequenced porcine RVAs from Brazil. We also analyzed archival strains that were isolated during the years of 1977–1992 as well as atypical strains involved in inter-species transmission between humans and pigs. We found that, in general, the genotype 1 genes of typical modern human Wa-like RVAs clustered together in phylogenetic trees and were separate from those of typical modern porcine RVAs. The only exception was for the NSP5/6 gene, which showed no host-specific phylogenetic clustering. Using amino acid sequence alignments, we identified 34 positions that differentiated the VP1-VP3, NSP2, and NSP3 genotype 1 proteins of typical modern human Wa-like RVAs versus typical modern porcine RVAs and documented how these positions vary in the archival/unusual isolates. No host-specific amino acid positions were identified for NSP4, NSP5, or NSP6. Altogether, the results of this study support the notion that human Wa-like RVAs and porcine RVAs are evolutionarily related, but indicate that some of their genotype 1 genes and proteins have diverged over time possibly as a reflection of sequestered replication and protein co-adaptation in their respective hosts.

Synanthropic rodents as virus reservoirs and transmitters

“…RVs are widely distributed in Brazil, and have been described in animals (both young and adults) such as cattle 105 , birds 106 , and pigs 107,108 . In rodents, there is a single report of RVA associated with swine production 109 .…”

Novel G9 rotavirus strains co-circulate in children and pigs, Taiwan

“…A recent study found that backbone genes of genotype 1 human and porcine strains can be distinguished by conserved patterns of amino acid substitutions within the VP1, VP2, VP3, NSP1, NSP2, and NSP3 proteins33. We performed analysis on these five proteins from the strains sampled and compared results with the reference strains sampled in the publication (Figs 6 and 7).…”

“…All samples had NSP2 proteins that shared multiple conserved sites with Wa-like human origin NSP2 proteins but also had substitutions at positions 97 and 282 that resembled to patterns seen in porcine strains (D and L, respectively). Moreover, this combination of aa substitutions was detected in many reference human and porcine RVA strains33. Thus, the genesis of NSP2 is difficult to discern, as the particular variable site pattern found in this protein is shared among various porcine and human strains33.…”

“…Moreover, this combination of aa substitutions was detected in many reference human and porcine RVA strains33. Thus, the genesis of NSP2 is difficult to discern, as the particular variable site pattern found in this protein is shared among various porcine and human strains33.…”

“…Sequences obtained from samples and reference sequences were aligned with MUSCLE and phylogenetic trees with 1,000 bootstraps replicates were created with neighbor-joining and maximum likehood methods with the best-fit substitution models determined by built-in model test application in MEGA639. Variable amino acid positions of VP1, VP2, VP3, NSP1, NSP2, and NSP3 were identified by aligning protein sequence in MEGA6 and visually inspecting each of the variable sites that were identified as previously described33.…”