Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells

Wilfried Posch, Marion Steger, Ulla Knackmuss, Michael Blatzer, Hanna Mari Baldauf, Wolfgang Doppler, Tommy E. White, Paul Hörtnagl, Felipe Diaz-Griffero, Cornelia Lass-Flörl, Hubert Hackl, Arnaud Moris, Oliver T. Keppler, Doris Wilflingseder

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Article numbere1005005
JournalPLoS pathogens
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2015

    Fingerprint

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Posch, W., Steger, M., Knackmuss, U., Blatzer, M., Baldauf, H. M., Doppler, W., White, T. E., Hörtnagl, P., Diaz-Griffero, F., Lass-Flörl, C., Hackl, H., Moris, A., Keppler, O. T., & Wilflingseder, D. (2015). Complement-Opsonized HIV-1 Overcomes Restriction in Dendritic Cells. PLoS pathogens, 11(6), [e1005005]. https://doi.org/10.1371/journal.ppat.1005005