HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits
Open Access
- 2 August 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 10 (9), 1008-1017
- https://doi.org/10.1038/ni.1753
Abstract
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.Keywords
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