Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells

PLoS Pathogens

Doris Wilflingseder¹  Paul Hörtnagl²  Tommy E. White³  Felipe Diaz-Griffero³  Hubert Hackl⁴  Wilfried Posch⁵  Cornelia Lass-Flörl⁵  Michael Blatzer⁵  Ulla Knackmuss⁵  Marion Steger⁵  Wolfgang Doppler⁶  Oliver T. Keppler⁷  Hanna-Mari Baldauf⁸  Arnaud Moris⁹ 

[1] CNRS, ERL 8255, Center for Immunology and Microbial Infections - CIMI-Paris, Paris, France;Central Institute for Blood Transfusion & Immunological Department, Medical University of Innsbruck, Innsbruck, Austria;Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America;Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria;Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria;Division of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria;INSERM, U1135, Center for Immunology and Microbial Infections - Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France;Institute of Medical Virology, University of Frankfurt, Frankfurt, Germany;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

关键词: HIV-1;    HIV;    Phosphorylation;    T cells;    Complement system;    Cytotoxic T cells;    Opsonization;    HIV-2;   

DOI  :  10.1371/journal.ppat.1005005

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY