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1: J Virol. 2007 Aug;81(15):8180-91. Epub 2007 May 16.
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MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands.

Meier A, Alter G, Frahm N, Sidhu H, Li B, Bagchi A, Teigen N, Streeck H, Stellbrink HJ, Hellman J, van Lunzen J, Altfeld M.

Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA.

Immune activation is a major characteristic of human immunodeficiency virus type 1 (HIV-1) infection and a strong prognostic factor for HIV-1 disease progression. The underlying mechanisms leading to immune activation in viremic HIV-1 infection, however, are not fully understood. Here we show that, following the initiation of highly active antiretroviral therapy, the immediate decline of immune activation is closely associated with the reduction of HIV-1 viremia, which suggests a direct contribution of HIV-1 itself to immune activation. To propose a mechanism, we demonstrate that the single-stranded RNA of HIV-1 encodes multiple uridine-rich Toll-like receptor 7/8 (TLR7/8) ligands that induce strong MyD88-dependent plasmacytoid dendritic cell and monocyte activation, as well as accessory cell-dependent T-cell activation. HIV-1-encoded TLR ligands may, therefore, directly contribute to the immune activation observed during viremic HIV-1 infection. These data provide an initial rationale for inhibiting the TLR pathway to directly reduce the chronic immune activation induced by HIV-1 and the associated immune pathogenesis.

Publication Types:
PMID: 17507480 [PubMed - indexed for MEDLINE]

PMCID: PMC1951290