The Envelope Glycoprotein Ectodomains Determine the Efficiency of CD4+ T Lymphocyte Depletion in Simian– Human Immunodeficiency Virus–Infected Macaques

Journal of Experimental Medicine - Tập 188 Số 6 - Trang 1159-1171 - 1998
Gunilla B. Karlsson1,2,3,4,5,6,7,8, Matilda Halloran1,2,3,4,5,6,7,8, Dominik Schenten1,2,3,4,5,6,7,8, Juliette Lee1,2,3,4,5,6,7,8, Paul Rácz1,2,3,4,5,6,7,8, Klara Tenner‐Racz1,2,3,4,5,6,7,8, Judith Manola1,2,3,4,5,6,7,8, Rebecca Gelman1,2,3,4,5,6,7,8, Bijan Etemad-Moghadam1,2,3,4,5,6,7,8, Elizabeth Desjardins1,2,3,4,5,6,7,8, Richard T. Wyatt1,2,3,4,5,6,7,8, Norma P. Gerard1,2,3,4,5,6,7,8, Luisa Marcon1,2,3,5,6,7,8, David Margolin1,2,3,4,5,6,7,8, John W. Fanton1,2,3,4,5,6,7,8, Michael K. Axthelm1,2,3,4,5,6,7,8, Norman L. Letvin1,2,3,4,5,6,7,8, Joseph Sodroski1,2,3,5,6,7,8
1From the *Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115; the ‡Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115; the §Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115; the ‖Department of Pathology and Korber Laboratory, Bernhard-Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; the ¶Department of Biostatistical Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115; the **Department of Medicine and Department of Pediatrics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115; the ††Institute of Microbiology, University of Padua Medical School, Padua 35121, Italy; and the §§Oregon Regional Primate Research Center, Beaverton, Oregon 97006-3499
2the Department of Biostatistical Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115
3the Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115,
4the Department of Medicine and Department of Pediatrics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115
5the Department of Pathology and Korber Laboratory, Bernhard-Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
6the Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115
7the Institute of Microbiology, University of Padua Medical School, Padua 35121, Italy
8the Oregon Regional Primate Research Center, Beaverton, Oregon 97006-3499

Tóm tắt

CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)–infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian–human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4+ T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4+ T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4+ T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.

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Journal of Experimental Medicine

Tập 188 Số 6

1159-1171

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