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Science  18 Sep 2009:
Vol. 325, Issue 5947, pp. 1477
DOI: 10.1126/science.325_1477a

A Nef-containing conduit linking macrophages.

CREDIT: XU ET AL., NAT. IMMUNOL. 10, 1008 (2009)

B cell–mediated immunity is compromised in HIV-infected individuals even though these cells are not infected by the virus. How does HIV do this? One clue comes from the recent observations that B cells can express the viral protein Nef and that these Nef-expressing B cells exhibit impaired immunoglobulin class switching, a process whereby B cells expand their immunoglobulin repertoires to include additional classes and thus enhance the response to pathogens. How Nef ends up in B cells, however, has been puzzling.

Xu et al. report that this occurs via long-range intercellular conduits formed between HIV-infected macrophages and B cells. Nef expression in macrophages drove conduit formation via an actin- and guanine nuclear exchange factor–dependent pathway. Nef then entered B cells via these conduits and once present in B cells, inhibited class switching. The authors then established the in vivo relevance of these findings by demonstrating that long-term nonprogressors (patients who have not developed AIDS) infected with Nef-deficient HIV showed evidence of normal class switching, whereas class switching was aberrant in patients harboring wild-type HIV.

Nat. Immunol. 10, 1008 (2009).

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