pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane

CD4 functions as the cell-surface receptor for human immunodeficiency virus (HIV); however, the mechanism of virus entry into susceptible cells is unknown. To explore this question we used a human T lymphoblastic cell line (VB) expressing high levels of surface CD4. Neutralization of endosomal compa...

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Bibliographic Details
Published inCell Vol. 49; no. 5; pp. 659 - 668
Main Authors Stein, Barry S., Gowda, Shantharaj D., Lifson, Jeffrey D., Penhallow, Robert C., Bensch, Klaus G., Engleman, Edgar G.
Format Journal Article
LanguageEnglish
Published Cambridge, MA Elsevier Inc 05.06.1987
Cell Press
Subjects
AIDS/HIV
Antigens, Differentiation, T-Lymphocyte
Antigens, Surface - physiology
Biological and medical sciences
Cell Line
Cell Membrane - microbiology
Fundamental and applied biological sciences. Psychology
HIV - physiology
human immunodeficiency virus
Humans
Hydrogen-Ion Concentration
lymphocytes T
Membrane Fusion
Microbiology
Microscopy, Electron
plasma membranes
Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains
T-Lymphocytes - microbiology
Virology
Virus
Membrane fusion
T-Lymphocyte
Plasma membrane
Retroviridae
PH
Virus replication cycle
Human immunodeficiency virus
Virus envelope
Host virus relation
Mechanism
Virus penetration
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Summary:CD4 functions as the cell-surface receptor for human immunodeficiency virus (HIV); however, the mechanism of virus entry into susceptible cells is unknown. To explore this question we used a human T lymphoblastic cell line (VB) expressing high levels of surface CD4. Neutralization of endosomal compartments (pH > 6.4) with lysosomotropic agents did not effectively inhibit HIV nucleocapsid entry into the cytoplasm, and virus treated at low pH (5.5) failed to induce rapid cell-to-cell fusion in uninfected cells. Electron microscopy of VB cells acutely exposed to HIV at neutral pH revealed direct fusion of the virus envelope with the plasma membrane within minutes at 4°C. No endocytosed virions were visualized upon rewarming the HIV-exposed cells to 37°C for as long as 60 min. These results indicate that HIV penetrates CD4-positive T cells via pH-independent membrane fusion.
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ISSN:0092-8674
1097-4172
DOI:10.1016/0092-8674(87)90542-3