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Whole Genome Sequencing for Rapid Characterization of Rabies Virus Using Nanopore Technology
Published on: August 18, 2023
Genetic diversity and molecular evolution of the rabies virus matrix protein gene in China
Hui Wu1, Lihua Wang, Xiaoyan Tao
1State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai St., Changping Dist., Beijing 102206, China.
Abstract:
To investigate the diversity of rabies virus (RABV) matrix protein (M) gene in the current Chinese rabies epidemic, we fully examined M gene of 63 street RABVs (Virus isolated from naturally infected animals), and performed phylogenetic and mutational analysis. Our results indicate that the Chinese RABV M gene is well conserved with 90.6% to 100% amino acid similarity. Analysis of the mutations indicates that the sequences can be divided into four groups with each group defined by distinct substitutions. The PPxY motif and residue E58, which are essential for efficient virus production and pathogenicity, were completely conserved. The estimated mean rate of nucleotide substitution was 4.6×10(-4) substitutions per site per year, and the estimated average time of the most recent common ancestor (TMRCA) was 265 years ago based on the M gene of Chinese street RABVs, which are similar to previously reported values for the glycoprotein (G) and nucleoprotein (N) gene. This indicates that the genomic RNA of RABVs circulating worldwide is stable; G, N and M genes are evolving at a similar rate. This study showed that although the Chinese RABV strains could be divided into distinct clades based on the phylogenetic analysis, their functional domains of M proteins were highly conserved.
Insights
Rabies virus (RABV) matrix protein (M) gene in China shows high amino acid conservation. Key functional domains remain stable, indicating conserved virus production and pathogenicity across diverse clades.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Rabies virus (RABV) poses a significant public health threat globally.
- Understanding the genetic diversity of circulating RABV strains is crucial for effective control strategies.
- The matrix protein (M) gene plays a vital role in virus assembly and release.
Purpose of the Study:
- To analyze the genetic diversity and evolutionary patterns of the RABV matrix protein (M) gene in China.
- To identify potential mutations and their impact on conserved functional domains.
- To estimate the evolutionary rate and time of the most recent common ancestor (TMRCA) of Chinese RABV strains.
Main Methods:
- Phylogenetic analysis of the M gene from 63 street RABV isolates.
- Amino acid similarity comparisons and mutational analysis.
- Estimation of nucleotide substitution rates and TMRCA.
Main Results:
- The Chinese RABV M gene exhibits high amino acid conservation (90.6%-100%).
- Mutational analysis revealed four distinct phylogenetic groups.
- Essential functional domains, including the PPxY motif and residue E58, were completely conserved.
- The estimated nucleotide substitution rate and TMRCA align with previous findings for other RABV genes (G and N).
Conclusions:
- Chinese RABV strains are phylogenetically distinct but share highly conserved functional domains in their M proteins.
- The M gene evolution rate is similar to other RABV genes, suggesting genomic RNA stability.
- Conserved functional domains imply stable virus production and pathogenicity mechanisms in circulating RABV.
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