Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells

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Posch, Wilfried | Steger, Marion | Knackmuss, Ulla | Blatzer, Michael | Baldauf, Hanna-Mari | Doppler, Wolfgang | White, Tommy E. | Hörtnagl, Paul | Diaz-Griffero, Felipe | Lass-Flörl, Cornelia | Hackl, Hubert | Moris, Arnaud | Keppler, Oliver T. | Wilflingseder, Doris

Edité par CCSD ; Public Library of Science -

International audience. DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus, DCs are productively infected only at very low levels with HIV-1, and this non-permissiveness of DCs is suggested to go along with viral evasion. We now illustrate that complement-opsonized HIV-1 (HIV-C) efficiently bypasses SAMHD1 restriction and productively infects DCs including BDCA-1 DCs. Efficient DC infection by HIV-C was also observed using single-cycle HIV-C, and correlated with a remarkable elevated SAMHD1 T592 phosphorylation but not SAMHD1 degradation. If SAMHD1 phosphorylation was blocked using a CDK2-inhibitor HIV-C-induced DC infection was also significantly abrogated. Additionally, we found a higher maturation and co-stimulatory potential, aberrant type I interferon expression and signaling as well as a stronger induction of cellular immune responses in HIV-C-treated DCs. Collectively, our data highlight a novel protective mechanism mediated by complement opsonization of HIV to effectively promote DC immune functions , which might be in the future exploited to tackle HIV infection.

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