TY - JOUR
T1 - Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells
AU - Posch, Wilfried
AU - Steger, Marion
AU - Knackmuss, Ulla
AU - Blatzer, Michael
AU - Baldauf, Hanna Mari
AU - Doppler, Wolfgang
AU - White, Tommy E.
AU - Hörtnagl, Paul
AU - Diaz-Griffero, Felipe
AU - Lass-Flörl, Cornelia
AU - Hackl, Hubert
AU - Moris, Arnaud
AU - Keppler, Oliver T.
AU - Wilflingseder, Doris
N1 - Funding Information:
We thank our technician Karolin Thurnes, and Dr Annelies Mühlbacher, Central Institute for Blood Transfusion & Immunological Department, for their valuable help and support regarding this manuscript. We thank Prof. Nikolaus Romani, Department of Dermatology & Venereology, Medical University of Innsbruck, Prof. Teunis Geijtenbeek, AMC Netherlands, and Prof. Manfred P. Dierich for discussing the manuscript. Additionally, we want to thank Prof. Olivier Schwartz, Institute Pasteur, and Prof. Stephan Geley, Division of Molecular Pathophysiology, Medical University of Innsbruck, for providing reagents. The authors also thank Polymun Scientific, Donaustrasse 99, Klosterneuburg, Austria who provided all reagents for p24 ELISA. The reagents ARP118 (HIV-BaL) and ARP177.8 (HIV-92UG037) were obtained from the Centre for AIDS Reagents, NIBSC HPA UK, supported by the EC FP6/7 Europrise Network of Excellence, and NGIN consortia and the Bill and Melinda Gates GHRC-CAVD Project and were donated by Dr. S. Gartner, Dr. M. Popovic, Dr. R. Gallo (Courtesy of the NIH AIDS Research and Reference Reagent Program [BaL]), and the WHO UN AIDS Network for HIV-isolation and characterization [92UG037].
Publisher Copyright:
© 2015 Posch et al.
PY - 2015/6/1
Y1 - 2015/6/1
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.
AB - 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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U2 - 10.1371/journal.ppat.1005005
DO - 10.1371/journal.ppat.1005005
M3 - Article
C2 - 26121641
AN - SCOPUS:84936763308
SN - 1553-7366
VL - 11
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 6
M1 - e1005005
ER -
