[Frontiers in Bioscience E2, 204-220, January 1, 2010]

Correlation of the virulence of CSFV with evolutionary patterns of E2 glycoprotein

Zhiyin Wu1, 2, Qin Wang3, Qian Feng1, Yingying Liu1, JunlinTeng1, Albert Cheunghai Yu4, Jianguo Chen1, 2

1The Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education and The State Key Laboratory of Bio-membrane and Membrane Bio-engineering, Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, P. R. China, 2The Center for Theoretical Biology, Peking University, Beijing 100871, P. R. China, 3Department of Inspection Technology Research, China Institute of Veterinary Drug Control, Beijing 100081, P.R.China, 4Neuroscience Research Institute and Infectious Disease Center, Health Science Center, Peking University, Beijing 100191, P.R.China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Methods
3.1. Dataset construction and phylogeny
3.2. Estimate of mean omega (ω) across the genome and testing for positive selection
3.3. Structural and functional analysis of positively selected sites within E2
4. Results
4.1. Phylogenetic analysis of CSFV sequences
4.2. Strength of positive selection on each protein encoding sequence of CSFV
4.3. Positively selected sites of each putative gene of CSFV genome
4.4. Maximum likelihood estimates of omega (ω) and detection of physicochemical selective pressures of E2 along specific lineage of CSFV
4.5. Evolutionary analysis of CSFV virulence
5. Discussion
6. Acknowledgement
7. References

1. ABSTRACT

Infection with classical swine fever virus (CSFV) is costly to the livestock industry. Several genomic sequences including velogenic strains and low virulent strains have been identified. However, the reasons for the virulence of the virus have remained unclear. Based on selective pattern and pressure strength, we classified all genes of CSFV into three classes. Among these genes, the E2 gene was under the strongest positive selection. Based on the analysis of 85 representative E2 gene sequences, the location and intensity of positive selection in CSFV isolates from group one and group two were identified. These results suggest that these two groups employ evolutionary difference. Moreover, the mutations, potentially driven by positive selection, can be correlated with the virulence of CSFV by altering the conformation and function of E2 and/or changing its glycosylation pattern. Based on these results, a model for the evolution of virulence of CSFV is proposed. The results provide a link between epidemiology and the gene function of CSFV, and may shed light on the molecular mechanism underlying the variation of CSFV virulence.