TY - JOUR A1 - Posch, Wilfried A1 - Steger, Marion A1 - Knackmuss, Ulla A1 - Blatzer, Michael A1 - Baldauf, Hanna-Mari A1 - Doppler, Wolfgang A1 - White, Tommy E. A1 - Hörtnagl, Paul A1 - Diaz-Griffero, Felipe A1 - Lass-Flörl, Cornelia A1 - Hackl, Hubert A1 - Moris, Arnaud A1 - Keppler, Oliver Till A1 - Wilflingseder, Doris T1 - Complement-opsonized HIV-1 overcomes restriction in dendritic cells T2 - PLoS pathogens N2 - 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. Y1 - 2015 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/38008 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-380087 SN - 1553-7374 SN - 1553-7366 N1 - Copyright: © 2015 Posch et al. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. VL - 11 IS - (6): e1005005 SP - 1 EP - 23 PB - PLoS CY - Lawrence, Kan. ER -