A history estimate and evolutionary analysis of rabies virus variants in China

Abstract

To investigate the evolutionary dynamics of rabies virus (RABV) in China, we collected and sequenced 55 isolates sampled from 14 Chinese provinces over the last 40 years and performed a coalescent-based analysis of the G gene. This revealed that the RABV currently circulating in China is composed of three main groups. Bayesian coalescent analysis estimated the date of the most recent common ancestor for the current RABV Chinese strains to be 1412 (with a 95 % confidence interval of 1006-1736). The estimated mean substitution rate for the G gene sequences (3.961¾10"4 substitutions per site per year) was in accordance with previous reports for RABV.Rabies has become an important public health concern in countries in Asia and Africa. It is estimated that this disease is responsible for over 55 000 human deaths annually, of which approximately 56 % occur in Asia and 44 % in Africa (WHO, 2005). Rabies was first described in China in about 556 BC and has been continually reported for the following 2500 years (Wang & Huang 2001 et al., 2005). In this study, we used Bayesian MCMC methods to analyse sequences from the highly variable G gene of RABV to determine phylogenetic relationships. By using G gene data collected over several years from almost all regions that had experienced cases of rabies, we investigated the evolution of RABV variants and determined the population history of RABV circulating in China.A total of 55 complete G gene sequences (1572 nt) isolated from four hosts (dog, human, cattle and deer) from 14The GenBank/EMBL/DDBJ accession numbers for the 25 RABV G gene sequences isolated in this study are FJ602447-FJ602459 and FJ418876-FJ418887. provinces, administrative municipalities and autonomous regions of China were analysed. The four hosts from which the viruses were isolated represent reservoirs and spillover hosts. Of these isolates, 25 were newly sequenced as part of this study (GenBank accession nos FJ602447-FJ602459) by using methods described previously (Meng et al., 2007); the remaining 30 isolates were obtained from GenBank. The year of isolation was available for all the isolates; full details are provided in Fig. 1 and Table 1.Estimates of the rate of molecular evolution, m (substitutions per site per year), and the time to most recent common ancestor (TMRCA) for the complete G gene alignment were obtained using a Bayesian MCMC method which was implemented in the BEAST program (available at http://beast.bio.ed.ac.uk/Main_Page). The best-fit model of nucleotide substitution for Bayesian analysis was selected with the MODELTEST software using Akaike's Information Criterion (AIC) (Posada & Crandall, 1998). The general time reversible (GTR) substitution model, incorporating a proportion of invariable sites (I) and a gamma distribution of rate variation among sites (C4) was used for the BEAST analysis. We employed both strict and relaxed (uncorrelated exponential and lognormal) molecular clocks (Drummond et al., 2006) to explore the extent of variation in the rate of nucleotide substitution and ...

The Spatial and Temporal Dynamics of Rabies in China

“…If the rabies in wildlife was a consequence of spillover from dogs, then we would expect to find the wildlife isolates mixed in with the dog samples. This hasn't been reported in previous studies which have either focused on dogs and only contained one or two wildlife samples [3], [4], [8], or contained more wildlife sequences but focused primarily on the epidemiology rather than the phylogenetic relationships between the strains [34]. Secondly, our study found the first evidence of a translocation event in wildlife in China.…”

“…While cases are relatively rare in developed countries, the virus has significant impact on a global scale, with more than 55,000 deaths reported annually [2], and represents a major public health issue in many countries. More than half of these cases occur in Asia and China has the second highest incidence of rabies after India [3], [4]; in the last 60 years several rabies epidemic waves have been reported in China and improving the understanding of how these epidemics emerge can help to determine how to best reduce the likelihood of future outbreaks. Human rabies cases in China decreased during the first half of the 1990s with a low of 159 cases reported in 1996 [5], [6], [7] but subsequently the number of human rabies cases increased dramatically, with 3,302 cases reported in 2007 [5].…”

“…There are already many published reports on the phylogenetic relationship amongst strains isolated in China that have primarily focused on sample classification and estimation of features such as date of the most recent common ancestor (TMRCA) [3], [4], [6], [7], [8], [9], [10]. In this work we have expanded on the work of previous studies by using a more complete sequence set consisting of sequences spanning a 720 nt region of the nucleocapsid gene that encompasses samples from the entire epidemic region.…”

Genetic and evolutionary characterization of RABVs from China using the phosphoprotein gene

“…There have been several previous estimates of RABVs substitution rates for the G gene (1.2-6.5 x10 -4 substitutions per site per year) and the N gene (1.1-5.6 x10 -4 substitutions per site per year) based on dog, fox and mongoose RABVs samples collected worldwide [25,27,35-38]. In this study, Bayesian coalescent analysis showed that mean substitution rate of the P gene for the Chinese RABVs isolates is 3.305×10 -4 substitutions per site per year, which indicates that the genome RNA of RABVs circulating worldwide is stable.…”

One misdated sequence of rabbit hemorrhagic disease virus prevents accurate estimation of its nucleotide substitution rate

“…Within a given viral species, published tip-calibrated Bayesian substitution rate estimates are often highly consistent (e.g. Influenza A virus [1-3] and Rabies virus [4-8]). However, for some viruses, such as rabbit hemorrhagic disease virus (RHDV), there is a significant discrepancy among published substitution rates [9-13].…”