Title | HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Xu W, Santini PA, Sullivan JS, He B, Shan M, Ball SC, Dyer WB, Ketas TJ, Chadburn A, Cohen-Gould L, Knowles DM, Chiu A, Sanders RW, Chen K, Cerutti A |
Journal | Nat Immunol |
Volume | 10 |
Issue | 9 |
Pagination | 1008-17 |
Date Published | 2009 Sep |
ISSN | 1529-2916 |
Keywords | Actins, B-Lymphocytes, CD40 Antigens, Cell Communication, Germinal Center, HIV Antibodies, HIV Core Protein p24, HIV-1, Humans, Immunoglobulin A, Immunoglobulin Class Switching, Immunoglobulin G, Macrophages, nef Gene Products, Human Immunodeficiency Virus, U937 Cells |
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. |
DOI | 10.1038/ni.1753 |
Alternate Journal | Nat Immunol |
PubMed ID | 19648924 |
Grant List | R01AI057653 / AI / NIAID NIH HHS / United States AI07621 / AI / NIAID NIH HHS / United States R01AI074378 / AI / NIAID NIH HHS / United States R01AI057653-S1 / AI / NIAID NIH HHS / United States |
Related Faculty:
Amy Chadburn, M.D.