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PMID: 9420271 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Distinct mechanisms trigger apoptosis in human immunodeficiency virus type 1-infected and in uninfected bystander T lymphocytes.

Journal of virology ·Vol. 72 ·No. 1 ·1998-01-00 ·Pages 660-70

Herbein G, Van Lint C, Lovett JL, Verdin E

Abstract

Apoptosis is a main feature of AIDS pathogenesis and is thought to play a role in the progressive decrease of CD4+ T lymphocytes in infected individuals. To determine whether apoptosis occurs in infected and/or in uninfected peripheral blood T lymphocytes, we have used a recombinant human immunodeficiency virus type 1 (HIV-1) infectious clone expressing the green fluorescent protein (GFP). Using flow cytometry, we have determined the incidence of apoptosis by either terminal transferase dUTP nick end labeling or annexin-V assays in different cell subpopulations, i.e., in CD4+ or CD8+ T cells that were GFP positive or negative. After HIV-1 infection of purified peripheral blood lymphocytes, we observed that apoptosis occurred mostly in infected CD4+ peripheral blood lymphocytes. Remarkably, the presence of monocyte-derived macrophages in the culture increased dramatically the apoptosis of uninfected bystander T lymphocytes, while apoptosis in HIV-infected T lymphocytes was not changed. We therefore demonstrate that HIV-induced apoptosis results from at least two distinct mechanisms: (i) direct apoptosis in HIV-infected CD4+ T lymphocytes and (ii) indirect apoptosis in uninfected T cells mediated by antigen-presenting cells.

MeSH Terms
Antigen-Presenting Cells/cytology,immunology,virology Apoptosis/immunology,physiology Base Sequence CD4-Positive T-Lymphocytes/cytology,immunology,virology CD8-Positive T-Lymphocytes/cytology,immunology,virology Cloning, Molecular DNA Primers/genetics Gene Expression Green Fluorescent Proteins HIV-1/genetics,pathogenicity,physiology Humans Luminescent Proteins/genetics Macrophages/immunology Mutation T-Lymphocytes/cytology,immunology,virology Virus Replication/genetics
Chemicals
DNA Primers Luminescent Proteins Green Fluorescent Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Herbein G
The Picower Institute for Medical Research, Manhasset, New York 11030, USA.
Van Lint C
Lovett J L
Verdin E
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1998-01-00
Pages
660-70
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC109420
Subset
IM
Grants
NIAID NIH HHS · AI40847-01A1 · United States
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