Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells

• Published in: PLoS pathogens Vol. 11; no. 6; p. e1005005
• Main Authors: Posch, Wilfried, Steger, Marion, Knackmuss, Ulla, Blatzer, Michael, Baldauf, Hanna-Mari, Doppler, Wolfgang, White, Tommy E, Hörtnagl, Paul, Diaz-Griffero, Felipe, Lass-Flörl, Cornelia, Hackl, Hubert, Moris, Arnaud, Keppler, Oliver T, Wilflingseder, Doris
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2015; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; CD4-Positive T-Lymphocytes - immunology; Colleges & universities; Complement System Proteins - immunology; Dendritic cells; Dendritic Cells - immunology; Experiments; Gene expression; HIV; HIV Infections - immunology; HIV-1 - immunology; Human health and pathology; Human immunodeficiency virus; Humans; Infections; Life Sciences; Lymphocytes; Phosphorylation; Rodents; Viral infections; Virus Replication - immunology
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1005005

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.