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110 Nef-Trafficking Intercellular Highways for HIV Evasion of Antibody Production

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

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 44
doi: 10.1097/01.qai.0000397300.56223.a7

Mount Sinai School of Medicine, Immunology Institute, Catalan Institute for Research and Advanced Studies, Barcelona Biomedical Research Park, IMIM-Hospital del Mar

Contact-dependent communication between immune cells generates protection, but also facilitates viral spread. 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 harboring 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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