Killing of primary CD4+ T cells by non-syncytium-inducing macrophage-tropic human immunodeficiency virus type 1.
Understanding the mechanism by which human immunodeficiency virus type 1 (HIV-1) kills CD4+ T lymphocytes is important to the development of therapeutic and prophylactic strategies. Recent studies have indicated that, in some cases, progression to AIDS is associated with the appearance of syncytium-inducing, T cell line-tropic HIV-1 variants. Nevertheless, approximately 50% of subjects with AIDS harbor only non-syncytium-inducing, macrophage-tropic (NSI-M) variants of HIV-1. In most asymptomatic patients, NSI-M HIV-1 isolates are the predominant virus type found. We report here that cytopathicity of NSI-M HIV-1 for primary CD4+ T lymphocytes can be directly detected in vitro. The extent of CD4+ T-cell killing was not completely correlated with the rate of viral replication, suggesting that other characteristics of HIV-1 contribute to its cytopathicity. Our findings suggest that: (i) direct killing by NSI-M HIV-1 may contribute to CD4+ T-lymphocyte depletion in vivo, and (ii) the determinants of HIV-1 cytopathicity for CD4+ T lymphocytes and cell tropism or syncytia-forming ability are not necessarily tightly linked.
Yu
X
X
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
McLane
M F
MF
Ratner
L
L
O'Brien
W
W
Collman
R
R
Essex
M
M
Lee
T H
TH
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D016923:Cell Death; D002478:Cells, Cultured; D005434:Flow Cytometry; D015726:Giant Cells / Q000276:immunology; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000821:virology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors; D014779:Virus Replication