MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands |
| |
| Authors: | Meier Angela Alter Galit Frahm Nicole Sidhu Harlyn Li Bin Bagchi Aranya Teigen Nickolas Streeck Hendrik Stellbrink Hans-Juergen Hellman Judith van Lunzen Jan Altfeld Marcus |
| |
| Affiliation: | Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129, USA. |
| |
| 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. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
