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Nature 407, 386-390 (21 September 2000) | doi:10.1038/35030124; Received 10 May 2000; Accepted 11 July 2000

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

Todd M. Allen1,2, David H. O'Connor1,2, Peicheng Jing1, John L. Dzuris3, Bianca R. Mothé1, Thorsten U. Vogel1, Ed Dunphy1, Max E. Liebl1, Carol Emerson1, Nancy Wilson1, Kevin J. Kunstman5, Xiaochi Wang6, David B. Allison7, Austin L. Hughes8, Ronald C. Desrosiers9, John D. Altman6, Steven M. Wolinsky5, Alessandro Sette3 & David I. Watkins1,10

  1. Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, Wisconsin 53715-1299, USA
  2. Epimmune, 5820 Nancy Ridge Drive, San Diego, California 92121 , USA
  3. Northwestern University Medical School , 303 East Chicago, Room 3-735 Tarry Building, Chicago, Illinois 60611-3008, USA
  4. Emory Vaccine Center, Emory University School of Medicine, G211 Rollins Research Building, 1510 Clifton Road, Atlanta, Georgia 30322, USA
  5. St. Luke's/Roosevelt Hospital, Obesity Research Center, 1090 Amsterdam Avenue, Suite 14B, New York, New York 10025, USA
  6. Department of Biological Sciences, 401 Coker Life Sciences, University of South Carolina, Columbia, South Carolina 29208, USA
  7. New England Regional Primate Research Center, One Pine Hill Drive, Southborough, Massachusetts 01772-9102, USA
  8. Dept. of Pathology and Laboratory Medicine, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706-1532, USA
  9. These authors contributed equally to this work

Correspondence to: David I. Watkins1,10 Correspondence and requests for materials should be addressed to D.I.W. (e-mail: Email: watkins@primate.wisc.edu).

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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.

  1. Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, Wisconsin 53715-1299, USA
  2. Epimmune, 5820 Nancy Ridge Drive, San Diego, California 92121 , USA
  3. Northwestern University Medical School , 303 East Chicago, Room 3-735 Tarry Building, Chicago, Illinois 60611-3008, USA
  4. Emory Vaccine Center, Emory University School of Medicine, G211 Rollins Research Building, 1510 Clifton Road, Atlanta, Georgia 30322, USA
  5. St. Luke's/Roosevelt Hospital, Obesity Research Center, 1090 Amsterdam Avenue, Suite 14B, New York, New York 10025, USA
  6. Department of Biological Sciences, 401 Coker Life Sciences, University of South Carolina, Columbia, South Carolina 29208, USA
  7. New England Regional Primate Research Center, One Pine Hill Drive, Southborough, Massachusetts 01772-9102, USA
  8. Dept. of Pathology and Laboratory Medicine, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706-1532, USA
  9. These authors contributed equally to this work

Correspondence to: David I. Watkins1,10 Correspondence and requests for materials should be addressed to D.I.W. (e-mail: Email: watkins@primate.wisc.edu).