A dominant role for CD8+-T-lymphocyte selection in simian immunodeficiency virus sequence variation.
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.
O'Connor
David H
DH
Wisconsin Primate Research Center, Department of Pathology, Laboratoty of Medicine, University of Wisconsin, 1300 University Ave., Madison, WI 53706, USA.
McDermott
Adrian B
AB
Krebs
Kendall C
KC
Dodds
Elizabeth J
EJ
Miller
Jacqueline E
JE
Gonzalez
Edna J
EJ
Jacoby
Timothy J
TJ
Yant
Levi
L
Piontkivska
Helen
H
Pantophlet
Ralph
R
Burton
Dennis R
DR
Rehrauer
William M
WM
Wilson
Nancy
N
Hughes
Austin L
AL
Watkins
David I
DI
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
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins