Editors' ChoiceHIV

The B cell follicle shields HIV

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Science Translational Medicine  11 Mar 2015:
Vol. 7, Issue 278, pp. 278ec42
DOI: 10.1126/scitranslmed.aaa9497

Unlike the vast majority of HIV-infected individuals who gradually progress to acquired immunodeficiency syndrome (AIDS) (progressors), a small fraction of HIV-infected individuals called “elite controllers” develop efficient immune responses against HIV that suppress viremia and maintain CD4+ T cell counts in the absence of antiretroviral therapy (ART). However, elite controllers do harbor persistent low levels of productive HIV in sites that have yet to be identified.

Using a nonhuman primate model of HIV infection—that is, simian immunodeficiency virus (SIV) infection in rhesus macaques—Fukazawa et al. found that productive infection of elite controllers but not progressors was highly restricted to follicular helper T (TFH) cells, a subset of effector/memory CD4+ T cells present in B cell follicles that help B cells to produce class-switched antibodies. Furthermore, they showed that the depletion of CD8+ cytotoxic T lymphocytes (CTLs) in elite controller monkeys led to a marked redistribution of productive SIV infection to non-TFH CD4+ T cells. Conversely, upon CTL recovery, the restriction of productive SIV infection to TFH cells was once again restored in elite controller monkeys. These data suggest that B cell follicles provide a sanctuary for SIV to escape from CTL-mediated elimination. Strikingly, the authors also showed that SIV RNA was preferentially localized to TFH cells present in B cell follicles in ART-treated monkeys, raising the possibility that B cell follicles could be the same hiding place for SIV and its human counterpart HIV in individuals undergone ART.

This study represents a major step towards the identification of cellular and anatomical reservoirs of HIV in individuals with immunologically or pharmacologically controlled virus replication. Current HIV-cure strategies rely on immune-mediated elimination of HIV antigen-positive cells following latent virus reactivation. This study suggests that the destruction of B cell follicles and the induction of sufficient CTLs capable of penetrating B cell follicles will be necessary to achieve total HIV elimination.

Y. Fukazawa et al., B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat. Med. 10.1038/nm.3781 (2015). [Abstract]

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