title: A dominant role for CD8+-T-lymphocyte selection in simian immunodeficiency virus sequence variation.
abstract: CD8(+) T lymphocytes (CD8-TL) select viral escape variants in both human immunodeficiency virus and simian immunodeficiency virus (SIV) infections. The frequency of CD8-TL viral escape as well as the contribution of escape to overall virus diversification has not been assessed. We quantified CD8-TL selection in SIV infections by sequencing viral genomes from 35 SIVmac239-infected animals at the time of euthanasia. Here we show that positive selection for sequences encoding 46 known CD8-TL epitopes is comparable to the positive selection observed for the variable loops of env. We also found that >60% of viral variation outside of the viral envelope occurs within recognized CD8-TL epitopes. Therefore, we conclude that CD8-TL selection is the dominant cause of SIV diversification outside of the envelope.
authors.affiliation: Wisconsin Primate Research Center, Department of Pathology, Laboratoty of Medicine, University of Wisconsin, 1300 University Ave., Madison, WI 53706, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.forename: Adrian B
authors.initials: AB
authors.lastname: McDermott
authors.forename: Kendall C
authors.initials: KC
authors.lastname: Krebs
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Dodds
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Miller
authors.forename: Edna J
authors.initials: EJ
authors.lastname: Gonzalez
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Jacoby
authors.forename: Levi
authors.initials: L
authors.lastname: Yant
authors.forename: Helen
authors.initials: H
authors.lastname: Piontkivska
authors.forename: Ralph
authors.initials: R
authors.lastname: Pantophlet
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: William M
authors.initials: WM
authors.lastname: Rehrauer
authors.forename: Nancy
authors.initials: N
authors.lastname: Wilson
authors.forename: Austin L
authors.initials: AL
authors.lastname: Hughes
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins