Cited by 295HIV Research and TreatmentCellular transport and secretionT-cell and Retrovirus Studies

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Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism

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McClure, M. O., Marsh, M., Weiss, R. A.·1988·The EMBO Journal

DOI 10.1002/j.1460-2075.1988.tb02839.xPMC PMC454348

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Abstract

The effect of weak bases (NH4Cl and amantadine) and carboxylic ionophores (monensin) on the infection of CD4 (T4) positive human cell lines by HIV-1 is examined. These reagents, which raise the pH of acidic intracellular organelles, fail to inhibit HIV-1 entry and the events leading to viral protein synthesis at concentrations inhibitory for low pH-dependent fusogenic enveloped viruses. The infectivity of VSV (HIV-1) pseudotypes is unaffected by weak bases at concentrations causing 95% plaque reduction of VSV in its own envelope. HIV-1 dependent cell--cell fusion (syncytium formation) occurs in medium maintained at pH 7.4-7.6, and virions are not irreversibly inactivated by incubation in acid medium. Our results show that HIV-1 entry and membrane fusion do not require exposure to low pH. The production of infectious HIV-1 particles, however, is inhibited in cells treated with NH4Cl.

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“Human immunodeficiency virus (HIV) infection is initiated by the virus binding to the cell surface after CD4 engagement and HIV-1 fusion with the plasma membrane (Stein et al., 1987; Maddon et al., 1988; McClure et al., 1988; Moore et al., 1997).”
Highly Conserved Regions within the Spike Proteins of Human Coronaviruses 229E and NL63 Determine Recognition of Their Respective Cellular Receptors
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Method
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SFV infection in CHO cells: cell-type specific restrictions to productive virus entry at the cell surface
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“Human immunodeficiency virus type 1 (HIV-1) delivers its genome to host cells by fusing its envelope with cellular membranes (37, 45, 52, 55).”
Background
V3 Loop region of the HIV-1 gpl20 envelope protein is essential for virus infectivity
Ivanoff, L. A., Dubay, J. W., Morris, J. F., Roberts, S. J., Gutshall, L. L., Sternberg, E. J., Hunter, E., Matthews, T. J., & Petteway, S. R. (1992) · Virology · doi:10.1016/0042-6822(92)90444-t · Cited by 101
Inhibition of HIV-1 endocytosis allows lipid mixing at the plasma membrane, but not complete fusion
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Background
Requirements for different components of the host cell cytoskeleton distinguish ecotropic murine leukemia virus entry via endocytosis from entry via surface fusion
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“Among the retroviruses, human immunodeficiency virus (25, 27, 28, 48), avian leukosis virus subgroup A (14), and amphotropic murine leukemia virus (28) appear to fuse at the cell surface, while mouse mammary tumor virus appears to fuse with endocytic vesicle membranes (37).”
Background
Functional interaction of constant and variable domains of human immunodeficiency virus type 1 gp120
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Background
Internalization and recycling of CD4 transfected into HeLa and NIH3T3 cells.
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Herpesvirus Entry into Host Cells Mediated by Endosomal Low pH
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Mechanisms of enveloped virus entry into animal cells
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Self-citation
Alteration of HIV-1 Infectivity and Neutralization by a Single Amino Acid Replacement in the V3 Loop Domain
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BackgroundInfluential
The role of CD4 in HIV binding and entry
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Maternal-Fetal Transmission of Human Immunodeficiency Virus: A Review of Possible Routes and Cellular Mechanisms of Infection
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BackgroundResult
Interaction of the influenza hemagglutinin fusion peptide with lipid bilayers: area expansion and permeation
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Background
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Background
HIV-1 Entry in SupT1-R5, CEM-ss, and Primary CD4+T Cells Occurs at the Plasma Membrane and Does Not Require Endocytosis
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BackgroundMethod
Mechanisms of Retrovirus Replication
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Replication-Competent Rhabdoviruses with Human Immunodeficiency Virus Type 1 Coats and Green Fluorescent Protein: Entry by a pH-Independent Pathway
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“Subsequent studies contradicted the initial reports: entry of HIV-1 and VSV(HIV) pseudotypes was shown to be resistant to agents that block endosomal acidification, and fusion of HIV-1 with the plasma membrane was observed (29, 42).”
Result
HIV‐1 Replication in Dendritic Cells Occurs Through a Tetraspanin‐Containing Compartment Enriched in AP‐3
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Background
Suramin inhibits in vitro infection by duck hepatitis B virus, rous sarcoma virus, and hepatitis delta virus
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Involvement of ADAM9 in Multinucleated Giant Cell Formation of Blood Monocytes
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Infectious Entry by Amphotropic as well as Ecotropic Murine Leukemia Viruses Occurs through an Endocytic Pathway
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BackgroundResultInfluential
Fusion of Rous sarcoma virus with host cells does not require exposure to low pH
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Authors: McClure, M. O., Marsh, M., & Weiss, R. A.
Affiliations: Institute of Cancer Research (GB)
ORCID: McClure, M. O.
Marsh, M.
Weiss, R. A.
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1988-02-01
Volume: 7
Issue: 2
Pages: 513-518
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1002/j.1460-2075.1988.tb02839.x
PMC: PMC454348
OpenAlex: W108460990
Cited by: 295
References: 46
Citations by year: 2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 5 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 6 · 2013: 7 · 2012: 11
FWCI: 6.89
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Wellcome Trust
Medical Research Council
Topics: Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords: HIV-1 infection, CD4+ T cells, membrane fusion, syncytium formation, ammonium chloride, amantadine, monensin, carboxylic ionophores, weak bases, viral protein synthesis
MeSH terms: Antigens, Differentiation, T-Lymphocyte, Cell Line, Cell Transformation, Viral, HIV, Humans, Hydrogen-Ion Concentration, Viral Envelope Proteins

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Human immunodeficiency virus infection of CD4-bearing cells occurs by a pH-independent mechanism

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