Gelin Xu

Evolutionary dynamics of rabies viruses highlights the importance of China rabies transmission in Asia

Rabies in Asia is emerging as a serious public health issue. To explore the possible origin, phylogenetic relationships, and evolutionary dynamics of Asian Rabies viruses (RABV), we examined 200 complete nucleoprotein (N) gene sequences from RABV isolates in the region. Phylogeny supported the classification of Asian RABVs into five distinct clusters in lyssavirus genotype 1. Our geospatial and temporal analyses demonstrated that China appears to be the prime source of Asian RABVs. Understanding of rabies transmission and associated human activities, such as dog translocation, can help rabies control and elimination in Asia through collaborative efforts or programs.

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

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 (3.961x10(-4) substitutions per site per year) was in accordance with previous reports for RABV.

Transmission dynamics of rabies in China over the last 40 years: 1969–2009

BACKGROUND Rabies is a serious reemerging zoonosis in China. The molecular evolution and transmission patterns of rabies virus inferred from historical data can provide guidelines for better disease control and prevention in the future. OBJECTIVES To investigate the epidemiology and evolutionary dynamics of the rabies virus in China. STUDY DESIGN The molecular evolution of 132 viral glycoprotein gene sequences of Chinese rabies viruses collected in 17 provinces and 3 municipalities between 1969 and 2009 was analyzed. RESULTS Phylogenetic analysis revealed that Chinese rabies viruses are subdivided into 6 lineages (A-F) within Lyssavirus genotype 1. Lineage A represents the widely dispersed cosmopolitan lineage while lineage B is closely related to Arctic-like rabies viruses. The remaining lineages (C-F) are typical of those circulating across much of Southeast Asia. The evolutionary rate for Chinese rabies virus was 1.532 x 10(-4) substitutions per site per year, and the corresponding common ancestor was in about 1115. CONCLUSIONS The phylogeographic structure demonstrated Chinese rabies viruses have been transmitted intra-provincially and extra-provincially due to human-related activities.

Molecular characterization of the complete genome of a street rabies virus WH11 isolated from donkey in China

The complete genomic sequence of a rabies virus isolate WH11, isolated from brain tissue of a rabid donkey in China, was determined and compared with other rabies viruses. This is the first Chinese street strain which was isolated from donkey and the entire length and organization of the virus was similar to that of other rabies viruses. Multiple alignments of amino acid sequences of the nucleoprotein, phosphoprotein, matrix protein, glycoprotein, and large protein of WH11 with those of other rabies viruses were undertaken to examine the conservative degree of functional regions. Phylogenetic analysis using the complete genomic sequence of WH11 determined that this isolate is most closely related with rabies viruses previously isolated in China and the attenuated Chinese vaccine strain CTN181.

Isolation and Identification of a Novel Rabies Virus Lineage in China with Natural Recombinant Nucleoprotein Gene

Rabies virus (RABV) causes severe neurological disease and death. As an important mechanism for generating genetic diversity in viruses, homologous recombination can lead to the emergence of novel virus strains with increased virulence and changed host tropism. However, it is still unclear whether recombination plays a role in the evolution of RABV. In this study, we isolated and sequenced four circulating RABV strains in China. Phylogenetic analyses identified a novel lineage of hybrid origin that comprises two different strains, J and CQ92. Analyses revealed that the virus 3′ untranslated region (UTR) and part of the N gene (approximate 500 nt in length) were likely derived from Chinese lineage I while the other part of the genomic sequence was homologous to Chinese lineage II. Our findings reveal that homologous recombination can occur naturally in the field and shape the genetic structure of RABV populations.

Reconstruction and expression of the MRI-contrast protein, ferritin, with recombinant rabies vectors

Attenuated recombinant rabies vector could be an ideal system for delivery of contrast agent gene for Magnetic Resonance Imaging (MRI) because of its neurotropic nature. In this study, the gene of a biomolecular contrast agent, ferritin, was successfully cloned into two rabies virus vectors, vaccine-based pCTN and street strain-based pNH. Recombinant virus granules were obtained and proved to express ferritin by RT-PCR after transfection of CTN-ferritin and NH-ferritin vector systems in BHK-21 cells. The recovered rabies virus-rCTN-ferritin was of similar ability to rNH-ferritin, which suggests the possibility of application of this safe and effective rabies vector system in delivery of diagnostic or therapeutic genes into the brain.

A comparison of complete genome sequences of a rabies virus chinese isolate SH06 with the vaccine strains

In this study, we determined the complete nucleotide and deduced amino acid sequence of a primary isolate of rabies virus (SH06) obtained from the brain of a rabid dog. The overall length of the genome was 11 924 nucleotides. Comparison of the genomic sequence showed the homology of SH06 at nucleotide level with full-length genomes of reference vaccine strains ranged from 82.2% with the PV strain to 86.9% with the CTN strain. A full-length genome-based phylogenetic analysis was performed with sequences available from GenBank. Phylogenetic analysis of the complete genome sequences indicated that the SH06 exhibited the highest homology with rabies street virus BD06 and CTN vaccine strain originated from China.

Molecular epidemiology and sequencing of the G-L intergenic region of rabies viruses isolated in China

A group of 25 rabies viruses (RABVs), recovered from 24 dogs and one human case, were collected from various areas in China between 2004 and 2006. Genetic and phylogenetic analyses of the G-L intergenic region were carried out in 25 street RABV isolates and CTN vaccine strains of 7 generations. The study was based on the comparison of a 519 bp nucleotide sequence, encompassing the G-L intergenic region. The nucleotide sequence homologies of Chinese street strains were from 95.5% to 100%. The phylogenetic analysis showed that all Chinese isolates clearly supported the placement of all Chinese viruses in Lyssavirus genotype 1 and they were distributed according to their geographical origins. All of the Chinese strains were closely related but they could still be divided into two groups: group of street strains and group of CTN strains. This study presents details about the molecular epidemiology of rabies viruses based on the sequences of the G-L Intergenic region.

Development of a relative potency test using ELISA for human rabies vaccines

The NIH potency test for human rabies vaccines has disadvantages for use, especially in developing countries where rabies is endemic and prophylaxis needs ample, rapid, and reliable vaccine supplies. In China, 60-75 million doses of human rabies vaccines are administered each year. Vaccine quality control is of paramount importance, as is the release of potency-validated vaccines. We intended to design an alternative to the NIH in vivo method, and developed a relative potency test using an ELISA. Using Pearsons correlation analysis, we found a close relationship between the rabies vaccine glycoprotein content in vitro and the potency values in vivo. We suggest the relative potency test developed here as a simplified method for human rabies vaccine quality control in China and a possible alternative to the NIH method.