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Journal of Virology, November 2000, p. 10690-10698, Vol. 74, No. 22
Department of Cancer Immunology and AIDS,
Dana-Farber Cancer Institute,1
Department of Pathology, Harvard Medical
School,2 and Department of Immunology
and Infectious Diseases, Harvard School of Public
Health,3 Boston, Massachusetts 02115
Received 9 June 2000/Accepted 19 August 2000
In established T-cell lines, the membrane-fusing capacity of the
human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins mediates cytopathic effects, both syncytium formation and single-cell lysis. Furthermore, changes in the HIV-1 envelope glycoproteins are
responsible for the increased CD4+ T-cell-depleting ability
observed in infected monkeys upon in vivo passage of simian-human
immunodeficiency virus (SHIV) chimeras. In this study, a panel of SHIV
envelope glycoproteins and their mutant counterparts defective in
membrane-fusing capacity were expressed in primary human
CD4+ T cells. Compared with controls, all of the functional
HIV-1 envelope glycoproteins induced cell death in primary
CD4+ T-cell cultures, whereas the membrane fusion-defective
mutants did not. Death occurred almost exclusively in envelope
glycoprotein-expressing cells and not in bystander cells. Under
standard culture conditions, most dying cells underwent lysis as single
cells. When the cells were cultured at high density to promote
syncytium formation, the envelope glycoproteins of the passaged,
pathogenic SHIVs induced more syncytia than those of the respective
parental SHIV. These results demonstrate that the HIV-1 envelope
glycoproteins induce the death of primary CD4+ T
lymphocytes by membrane fusion-dependent processes.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Importance of Membrane Fusion Mediated by Human
Immunodeficiency Virus Envelope Glycoproteins for Lysis of Primary
CD4-Positive T Cells
*
Corresponding author. Mailing address: Department of
Cancer Immunology and AIDS, 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.
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