title: Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells.
abstract: 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.
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Posch
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Marion
authors.initials: M
authors.lastname: Steger
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Ulla
authors.initials: U
authors.lastname: Knackmuss
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Blatzer
authors.affiliation: Institute of Medical Virology, University of Frankfurt, Frankfurt, Germany.
authors.forename: Hanna-Mari
authors.initials: HM
authors.lastname: Baldauf
authors.affiliation: Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Doppler
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
authors.forename: Tommy E
authors.initials: TE
authors.lastname: White
authors.affiliation: Central Institute for Blood Transfusion & Immunological Department, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Hörtnagl
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
authors.forename: Felipe
authors.initials: F
authors.lastname: Diaz-Griffero
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.affiliation: Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Hackl
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC)-Paris 6, Center for Immunology and Microbial Infections - Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France; INSERM, U1135, Center for Immunology and Microbial Infections - Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France; CNRS, ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France; Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Department of Immunology, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Moris
authors.affiliation: Institute of Medical Virology, University of Frankfurt, Frankfurt, Germany.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Keppler
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Wilflingseder
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D014779:Virus Replication / Q000276:immunology
chemical_list: D003165:Complement System Proteins