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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“Myra and Robin collaborated with Mark Marsh to show that unlike viruses such as influenza, which fuse with cells from within endosomes via a low-pH-induced conformational switch, HIV-1 fuses with T cells at neutral pH [10] (Figure 1b).”

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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