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

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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

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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, Chadburn, Amy, Cohen-Gould, Leona, Knowles, Daniel M, Chiu, April, Sanders, Rogier W, Chen, Kang, Cerutti, Andrea·2009·Nature Immunology

DOI 10.1038/ni.1753PMC PMC2784687

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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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Retracted
RETRACTED ARTICLE: Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells
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See all 302

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: Xu, Weifeng
Shan, Meimei
Dyer, Wayne B
Ketas, Thomas J
Chadburn, Amy
Chiu, April
Sanders, Rogier W
Chen, Kang
Cerutti, Andrea
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2009-08-02
Volume: 10
Issue: 9
Pages: 1008-1017
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.1753
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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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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