MBE Advance Access published online on December 11, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl194
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Research Article |
Adaptation of a Diverse Simian Immunodeficiency Virus Population to a New Host is Revealed Through a Systematic Approach to Identify Amino Acid Sites Under Selection
1 Program in Population Biology, Evolution, and Ecology, and Emory Vaccine Center, Emory University, Atlanta, GA, USA
2 Current Address: Centers for Disease Control and Prevention, Division of Bacterial and Mycotic Diseases, Atlanta, GA, USA
3 Departments of Medicine, and Microbiology and Immunology, and Emory Vaccine Center, Emory University, Atlanta, GA, USA
4 Current Address: Merck Vaccine Division, Merck and Company, Inc., West Point, PA, USA
5 University of Iowa, Department of Biological Sciences, Roy J. Carver Center for Comparative Genomics, 310 Biology Building, Iowa City, IA 52242-1324, tel: (319) 335-1082, fax: (319) 335-1069
* Corresponding Author. email: john-logsdon{at}uiowa.edu
Simian immunodeficiency viruses (SIV) have had considerable success at crossing species barriers; both HIV-1 and HIV-2 have been transmitted on multiple occasions from SIV-infected natural host species. However, the precise evolutionary and ecological mechanisms characterizing a successful cross-species transmission event remain to be elucidated. Here, in addition to expanding and clarifying our previous description of the adaptation of a diverse, naturally occurring SIVsm inoculum to a new rhesus macaque host, we present an analytical framework for understanding the selective forces driving viral adaptation to a new host. A preliminary analysis of large-scale changes in virus population structure revealed that viruses replicating in the macaques were subject to increasing levels of selection through day 70 post infection, while contemporaneous viruses in the mangabeys remained similar to the source inoculum. Three different site-by-site methods were employed to identify the amino acid sites responsible for this macaque-specific selection. Of 124 amino acid sites analyzed, three codons in V2, a two amino acid shift in an N-linked glycosylation site and variation at two sites in the highly charged region, were consistently evolving under either directional or diversifying selection at days 40 and 70 post infection. This strong macaque-specific selection on the V2 loop underscores the importance of this region in the adaptation of SIVsm to rhesus macaques. Due to the extreme viral diversity already extant in the naturally occurring viral inoculum we employed a broad range of phylogenetic and numerical tools in order to distinguish the signatures of past episodes of selection in viral sequences from more recent selection pressures.
Key Words: SIV • Selection • Zoonosis • Quasispecies • Macaca mulatta • Cercocebus atys
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