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Cited by 427HIV Research and Treatmentinterferon and immune responsesImmune Response and Inflammation

A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells

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Manel, Nicolas, Hogstad, Brandon, Wang, Yaming, Levy, David E., Unutmaz, Derya, Littman, Dan R.·2010·Nature
DOI 10.1038/nature09337PMC PMC3051279
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Abstract

Dendritic cells serve a key function in host defence, linking innate detection of microbes to activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of human immunodeficiency virus (HIV) by host innate pattern-recognition receptors and subsequent coupling to antiviral T-cell responses is not yet known. Dendritic cells are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. Here we show that, when dendritic cell resistance to infection is circumvented, HIV-1 induces dendritic cell maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly synthesized HIV-1 capsid with cellular cyclophilin A (CYPA) and the subsequent activation of the transcription factor IRF3. Because the peptidylprolyl isomerase CYPA also interacts with HIV-1 capsid to promote infectivity, our results indicate that capsid conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell-intrinsic sensor for HIV-1 exists in dendritic cells and mediates an antiviral immune response, but it is not typically engaged owing to the absence of dendritic cell infection. The virulence of HIV-1 may be related to evasion of this response, the manipulation of which may be necessary to generate an effective HIV-1 vaccine.

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  • CypA binding of capsid has only been seen with lentiviruses.

    “However, CypA binding of capsid has only been seen with lentiviruses”

    From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [63]

    The paper reports CypA binding to HIV-1 capsid and, in the passage discussing HIV-2 (section labelled Abstract; page unavailable), notes the reported ability of HIV-2 capsid to bind human CypA. It does not say that capsid binding to CypA has been seen only in lentiviruses; that exclusive qualifier is unsupported. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Manel, N., Hogstad, B., Wang, Y., Levy, D. E., Unutmaz, D., & Littman, D. R.
Affiliations
  • New York University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Littman, Dan R.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2010-09-09
Volume
467
Issue
7312
Pages
214-217
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature09337
PMC
PMC3051279
OpenAlex
W2019039109
Cited by
427
References
4
Citations by year
2026: 3 · 2025: 9 · 2024: 11 · 2023: 18 · 2022: 11 · 2021: 22 · 2020: 16 · 2019: 16 · 2018: 28 · 2017: 32 · 2016: 30 · 2015: 37 · 2014: 49 · 2013: 42 · 2012: 55
FWCI
16.34
Type
journal article
Language
en
Update notices
erratum (2011-02-16)
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • Cancer Research Institute
  • Johns Hopkins University
  • York University
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (AI 28900, AI 33856, R01AI033856, U54AI057168, R21AI084633, R01AI065303, U54AI057158, R01AI028900)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
HIV-1, dendritic cells, innate immunity, type I interferon, Vpx, SIVmac, capsid, cyclophilin A, IRF3, dendritic cell maturation, T cell activation, HIV pathogenesis, vaccine design, HIV infectivity, peptidylprolyl isomerase, antiviral immune evasion
MeSH terms
Cell Line, Dendritic Cells, Humans, Immunity, Innate, Lymphocyte Activation, Monocytes, T-Lymphocytes, HIV-1, HIV Infections, Cyclophilin A, Capsid Proteins, Interferon Regulatory Factor-3

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