Cited by 302HIV Research and TreatmentT-cell and B-cell ImmunologyHIV-related health complications and treatments

HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits

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Xu, Weifeng, Santini, Paul A, Sullivan, John S, He, Bing, Shan, Meimei, Ball, Susan C, Dyer, Wayne B, Ketas, Thomas J +7 more·2009·Nature Immunology

Abstract

Contact-dependent communication between immune cells generates protection but also facilitates viral spread. Here we found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type 1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine-exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients with Nef-deficient virions, our data suggest that HIV-1 exploits intercellular 'highways' as a 'Trojan horse' to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entry.

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Crossref · 10.1038/ni.1753

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  • Nef mediates formation of TNTs in infected macrophages via M-sec and by enhancing production of myosin-X; Nef translocates from HIV-1-infected macrophages to B cells through nanotubes, inhibiting production of antiviral IgG2 and IgA.

    “The HIV accessory protein, Nef, has been reported to mediate the formation of TNTs in infected macrophages via the cellular protein M-sec [113], and by enhancing the production of the motor protein myosin-X [114]. Moreover, Nef is capable of translocating from HIV-1-infected macrophages to B cells through nanotubes, where it exerts anti-immune activity by inhibiting the production of antiviral IgG”

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Authors
Xu, W., Santini, P. A., Sullivan, J. S., He, B., Shan, M., Ball, S. C., Dyer, W. B., Ketas, T. J., Chadburn, A., Cohen-Gould, L., Knowles, D. M., Chiu, A., Sanders, R. W., Chen, K., & Cerutti, A.
Affiliations
  • Cornell University (US)
  • The University of Sydney (AU)
  • Icahn School of Medicine at Mount Sinai (US)
  • Northwestern University (US)
  • Amsterdam UMC Location University of Amsterdam (NL)
Corresponding author
Cerutti, Andrea
Venue
Nature Immunology
Published
2009-08-02
Volume
10
Issue
9
Pages
1008-1017
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W1968201178
Cited by
302
References
57
Citations by year
2026: 4 · 2025: 11 · 2024: 14 · 2023: 11 · 2022: 11 · 2021: 14 · 2020: 20 · 2019: 13 · 2018: 15 · 2017: 16 · 2016: 14 · 2015: 18 · 2014: 21 · 2013: 18 · 2012: 32
FWCI
11.95
Type
journal article
Language
en
Open access
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
National Institute of Allergy and Infectious Diseases (R01AI074378, R01AI057653-S1, AI 07621, T32AI007621, R01AI057653)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
Keywords
HIV-1, Nef protein, macrophages, B cells, IgG2, IgA, class switch recombination, guanine nucleotide exchange factor, mucosal immunity
MeSH terms
Actins, B-Lymphocytes, Cell Communication, Humans, Immunoglobulin A, Immunoglobulin G, Macrophages, HIV Antibodies, HIV-1, HIV Core Protein p24, Immunoglobulin Class Switching, Germinal Center, CD40 Antigens, U937 Cells, nef Gene Products, Human Immunodeficiency Virus

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