Computational Analysis Suggests That Lyssavirus Glycoprotein Gene Plays a Minor Role in Viral Adaptation

Kevin Tang,Xianfu Wu

doi:10.4061/2011/143498

Abstract

The Lyssavirus glycoprotein (G) is a membrane protein responsible for virus entry and protective immune responses. To explore possible roles of the glycoprotein in host shift or adaptation of Lyssavirus, we retrieved 53 full-length glycoprotein gene sequences from NCBI GenBank. The sequences were from different host isolates over a period of 70 years in 21 countries. Computational analyses detected 1 recombinant (AY987478, a dog isolate of CHAND03, genotype 1 in India) with incongruent phylogenetic support. No recombination was detected when AY98748 was excluded in the analyses. We applied different selection models to identify selection pressure on the glycoprotein gene. One codon at amino acid residual 483 was found to be under weak positive selection with marginal probability of 95% by using the maximum likelihood method. We found no significant evidence of positive selection on any site of the glycoprotein gene when the putative recombinant AY987478 was excluded. The computational analyses suggest that the G gene has been under purifying selection and that the evolution of the G gene may not play a significant role in Lyssavirus adaptation.

Highlights

Positive selection and recombination are important mechanisms in microbial pathogen adaption to new hosts, resistance to antibiotics, and evasion of immune responses [1]
Rabies virus is a single-stranded negative RNA virus belonging to the order Mononegavirales, family Rhabdoviridae, genus Lyssavirus, which causes rabies in all warm-blooded mammals
We found no significant evidence for positive selection pressure on any site of the G gene

Summary

Introduction

Positive selection and recombination are important mechanisms in microbial pathogen adaption to new hosts, resistance to antibiotics, and evasion of immune responses [1]. RNA viruses have high mutation rates due to lack of both proofreading and postreplicative repair activities associated with RNA replicases and reverse transcriptases [2], which benefits RNA viruses in adapting to the changing environment. Recombination is a general phenomenon in evolution and plays a significant role in viral fitness [3, 4]. Host shift and spillover events are frequently reported in rabies [5,6,7,8,9]. The role of the G gene in rabies spillover, host shift, and adaptation has not been analyzed thoroughly. The information could help understand viral pathogenesis and develop a vaccine for a broad spectrum of lyssavirus infections

Methods

Results

Conclusion