MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands

A Meier, G Alter, N Frahm, H Sidhu, B Li… - Journal of …, 2007 - Am Soc Microbiol
A Meier, G Alter, N Frahm, H Sidhu, B Li, A Bagchi, N Teigen, H Streeck, HJ Stellbrink…
Journal of virology, 2007Am Soc Microbiol
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 …
Abstract
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.
American Society for Microbiology