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© The Rockefeller University Press, 0022-1007/1998/9/1159/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 6, September 21, 1998 1159-1171

Articles

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

Gunilla B. Karlsson*, Matilda Halloran§, Dominik Schenten*, Juliette Lee*, Paul Racz||, Klara Tenner-Racz||, Judith Manola, Rebecca Gelman, Bijan Etemad-Moghadam*, Elizabeth Desjardins*, Richard Wyatt*, Norma P. Gerard**, Luisa Marcon*,{dagger}{dagger}, David Margolin{ddagger}, John Fanton§§, Michael K. Axthelm§§, Norman L. Letvin{ddagger}, and Joseph Sodroski*,{ddagger}

From the * Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115; the {ddagger} 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 {dagger}{dagger} Institute of Microbiology, University of Padua Medical School, Padua 35121, Italy; and the §§ Oregon Regional Primate Research Center, Beaverton, Oregon 97006-3499

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.

Key Words: simian–human immunodeficiency virus • Rhesus macaques • envelope glycoprotein • CD4+ T lymphocyte depletion • pathogenesis

Address correspondence to Joseph Sodroski, Dana-Farber Cancer Institute, 44 Binney St., JFB 824, Boston, MA 02115. Phone: 617-632-3371; Fax: 617-632-4338; E-mail: Joseph_Sodroski{at}dfci.harvard.edu

Abbreviations used: CAT, chloramphenicol acetyltransferase; MIP, macrophage inflammatory protein; RT, reverse transcriptase; sCD4, human soluble CD4; SHIV, simian–human immunodeficiency virus; SIV, simian immunodeficiency virus.


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