Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia

Todd M. Allen, David H. O'Connor, Peicheng Jing, John L. Dzuris, Bianca R. Mothé, Thorsten U. Vogel, Ed Dunphy, Max E. Liebl, Carol Emerson, Nancy Wilson, Kevin J. Kunstman, Xiaochi Wang, David B. Allison, Austin L. Hughes, Ronald C. Desrosiers, John D. Altman, Steven M. Wolinsky, Alessandro Sette and David I. Watkins ()
Additional contact information
Todd M. Allen: Wisconsin Regional Primate Research Center, University of Wisconsin
David H. O'Connor: Wisconsin Regional Primate Research Center, University of Wisconsin
Peicheng Jing: Wisconsin Regional Primate Research Center, University of Wisconsin
John L. Dzuris: Epimmune
Bianca R. Mothé: Wisconsin Regional Primate Research Center, University of Wisconsin
Thorsten U. Vogel: Wisconsin Regional Primate Research Center, University of Wisconsin
Ed Dunphy: Wisconsin Regional Primate Research Center, University of Wisconsin
Max E. Liebl: Wisconsin Regional Primate Research Center, University of Wisconsin
Carol Emerson: Wisconsin Regional Primate Research Center, University of Wisconsin
Nancy Wilson: Wisconsin Regional Primate Research Center, University of Wisconsin
Kevin J. Kunstman: Northwestern University Medical School
Xiaochi Wang: Emory Vaccine Center, Emory University School of Medicine, G211 Rollins Research Building
David B. Allison: St. Luke’s/Roosevelt Hospital, Obesity Research Center
Austin L. Hughes: 401 Coker Life Sciences, University of South Carolina
Ronald C. Desrosiers: New England Regional Primate Research Center
John D. Altman: Emory Vaccine Center, Emory University School of Medicine, G211 Rollins Research Building
Steven M. Wolinsky: Northwestern University Medical School
Alessandro Sette: Epimmune
David I. Watkins: Wisconsin Regional Primate Research Center, University of Wisconsin

Nature, 2000, vol. 407, issue 6802, 386-390

Abstract: Abstract Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop1,2. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection3,4,5,6,7,8,9,10,11, the data have been controversial12,13. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development.

Date: 2000
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DOI: 10.1038/35030124

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