Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Nature immunology, 2009-09, Vol.10 (9), p.1008-1017

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• Patients infected with human immunodeficiency virus (HIV) have profoundly dysfunctional T and B cell populations. Cerutti and colleagues show that HIV-infected macrophages form long-range conduits that deliver the immunosuppressive HIV protein Nef to distal B cells, inhibiting their function. 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.