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Cited by 160HIV Research and TreatmentInflammasome and immune disordersinterferon and immune responses

Cell-to-Cell Transmission of HIV-1 Is Required to Trigger Pyroptotic Death of Lymphoid-Tissue-Derived CD4 T Cells

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Galloway, Nicole L.K., Doitsh, Gilad, Monroe, Kathryn M., Yang, Zhiyuan, Muñoz-Arias, Isa, Levy, David N., Greene, Warner C.·2015·Cell Reports
DOI 10.1016/j.celrep.2015.08.011PMC PMC4565731
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Abstract

The progressive depletion of CD4 T cells underlies clinical progression to AIDS in untreated HIV-infected subjects. Most dying CD4 T cells correspond to resting nonpermissive cells residing in lymphoid tissues. Death is due to an innate immune response against the incomplete cytosolic viral DNA intermediates accumulating in these cells. The viral DNA is detected by the IFI16 sensor, leading to inflammasome assembly, caspase-1 activation, and the induction of pyroptosis, a highly inflammatory form of programmed cell death. We now show that cell-to-cell transmission of HIV is obligatorily required for activation of this death pathway. Cell-free HIV-1 virions, even when added in large quantities, fail to activate pyroptosis. These findings underscore the infected CD4 T cells as the major killing units promoting progression to AIDS and highlight a previously unappreciated role for the virological synapse in HIV pathogenesis.

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  • HIV cell-to-cell transmission, but not cell-free virions, induces pyroptotic death of target cells, limiting infectious spread via cell contacts.

    “Despite some evidence that VS can promote HIV spread in vivo, Galloway et al. showed that HIV cell-to-cell transmission, but not cell-free virions, induces pyroptotic death of target cells, limiting the infectious spread via cell contacts [134].”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [134]

    The Results and Discussion report that cell-to-cell transmission triggers pyroptotic death in resting, nonpermissive lymphoid CD4 T cells, whereas cell-free virions do not. The Discussion says this response acts against HIV-1 in those targets, but does not establish that pyroptosis limits infectious spread via cell contacts generally; it describes cell-to-cell spread between permissive cells as highly efficient. Page numbers are unavailable in our copy. (LLM, conf=0.84)

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Authors
Galloway, N. L. K., Doitsh, G., Monroe, K. M., Yang, Z., Muñoz-Arias, I., Levy, D. N., & Greene, W. C.
Affiliations
  • Gladstone Institutes (US)
  • New York University (US)
Corresponding author
  • Doitsh, Gilad
  • Greene, Warner C.
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2015-09
Volume
12
Issue
10
Pages
1555-1563
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2015.08.011
PMC
PMC4565731
OpenAlex
W1871039033
Cited by
160
References
2
Citations by year
2026: 6 · 2025: 10 · 2024: 11 · 2023: 12 · 2022: 13 · 2021: 12 · 2020: 12 · 2019: 18 · 2018: 14 · 2017: 19 · 2016: 28 · 2015: 5
FWCI
11.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • A.P. Giannini Foundation
  • National Institutes of Health (AI 096113, AI027763)
  • University of California, San Francisco (P30AI027763)
  • National Institute on Drug Abuse (DP1DA036502)
  • National Institute of Allergy and Infectious Diseases (R56AI118453, AI027763, R21AI102782, R01AI078783, AI-096113, U19AI096113, T32AI060537, P30AI027763)
  • National Center for Chronic Disease Prevention and Health Promotion (1DP1036502)
  • National Institute on Minority Health and Health Disparities (L60 MD003100)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
HIV-1, cell-to-cell transmission, pyroptosis, CD4+ T cells, lymphoid tissue, IFI16, inflammasome, caspase-1, virological synapse, innate immune response, AIDS progression, programmed cell death
MeSH terms
Cells, Cultured, Humans, Lymphoid Tissue, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Cell Adhesion Molecules, Apoptosis, Coculture Techniques, Caspase 1

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