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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.

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Acknowledgements

We thank L. Smith and B. Becker for preparation of this manuscript and C. D. Pauza and the Immunology and Virology Core Laboratory for infection with molecularly cloned SIVMAC239 nef stop and monitoring of macaques. This work was supported by the NIAID, NCRR and the The James B. Pendleton Charitable Trust. D.I.W. is an Elizabeth Glaser scientist.

Author information

Author notes

    • Todd M. Allen
    •  & David H. O'Connor

    These authors contributed equally to this work

Affiliations

  1. *Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, Wisconsin 53715-1299, USA

    • Todd M. Allen
    • , David H. O'Connor
    • , Peicheng Jing
    • , Bianca R. Mothé
    • , Thorsten U. Vogel
    • , Ed Dunphy
    • , Max E. Liebl
    • , Carol Emerson
    • , Nancy Wilson
    •  & David I. Watkins
  2. ‡Epimmune, 5820 Nancy Ridge Drive, San Diego, California 92121 , USA

    • John L. Dzuris
    •  & Alessandro Sette
  3. Northwestern University Medical School , 303 East Chicago, Room 3-735 Tarry Building, Chicago, Illinois 60611-3008, USA

    • Kevin J. Kunstman
    •  & Steven M. Wolinsky
  4. ¶Emory Vaccine Center, Emory University School of Medicine, G211 Rollins Research Building, 1510 Clifton Road, Atlanta, Georgia 30322, USA

    • Xiaochi Wang
    •  & John D. Altman
  5. #St. Luke’s/Roosevelt Hospital, Obesity Research Center, 1090 Amsterdam Avenue, Suite 14B, New York, New York 10025, USA

    • David B. Allison
  6. Department of Biological Sciences, 401 Coker Life Sciences, University of South Carolina, Columbia, South Carolina 29208, USA

    • Austin L. Hughes
  7. **New England Regional Primate Research Center, One Pine Hill Drive, Southborough, Massachusetts 01772-9102, USA

    • Ronald C. Desrosiers
  8. ††Dept. of Pathology and Laboratory Medicine, University of Wisconsin, 1300 University Avenue, Madison, Wisconsin 53706-1532, USA

    • David I. Watkins

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Correspondence to David I. Watkins.

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https://doi.org/10.1038/35030124

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