%0 Journal Article
%T Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells
%A Wilfried Posch&nbsp
%A Marion Steger&nbsp
%A Ulla Knackmuss&nbsp
%A Michael Blatzer&nbsp
%A Hanna-Mari Baldauf&nbsp
%A Wolfgang Doppler&nbsp
%A Tommy E. White&nbsp
%A Paul H£¿rtnagl&nbsp
%A Felipe Diaz-Griffero&nbsp
%A Cornelia Lass-Fl£¿rl
%J PLOS Pathogens
%D 2015
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1005005
%X 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.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1005005