MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands.
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MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands. / 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.
In: J VIROL, Vol. 81, No. 15, 15, 2007, p. 8180-8191.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands.
AU - Meier, Angela
AU - Alter, Galit
AU - Frahm, Nicole
AU - Sidhu, Harlyn
AU - Li, Bin
AU - Bagchi, Aranya
AU - Teigen, Nickolas
AU - Streeck, Hendrik
AU - Stellbrink, Hans-Juergen
AU - Hellman, Judith
AU - van Lunzen, Jan
AU - Altfeld, Marcus
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 81
SP - 8180
EP - 8191
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 15
M1 - 15
ER -
