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HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits
Open accessAbstract
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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“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”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [115]
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Metadata
- 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
- ORCID
- Venue
- Nature Immunology
- Published
- 2009-08-02
- Volume
- 10
- Issue
- 9
- Pages
- 1008-1017
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2784687
- 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
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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 › Infectious Diseases › 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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