Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production

PLoS One. 2014 Jul 18;9(7):e102395. doi: 10.1371/journal.pone.0102395. eCollection 2014.

Abstract

Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SP-D against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Antigens / chemistry
  • CD4 Antigens / metabolism*
  • Cervix Uteri / virology
  • Cytokines / biosynthesis*
  • Cytokines / metabolism
  • Female
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / metabolism*
  • HIV-1 / drug effects*
  • HIV-1 / metabolism
  • HIV-1 / physiology
  • Humans
  • Inflammation / metabolism
  • Jurkat Cells
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Docking Simulation
  • Monocytes / drug effects
  • Monocytes / virology
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Protein Conformation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pulmonary Surfactant-Associated Protein D / chemistry
  • Pulmonary Surfactant-Associated Protein D / metabolism
  • Pulmonary Surfactant-Associated Protein D / pharmacology*
  • Semen / virology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / virology
  • Vagina / virology
  • Virus Internalization / drug effects

Substances

  • CD4 Antigens
  • Cytokines
  • HIV Envelope Protein gp120
  • Pulmonary Surfactant-Associated Protein D
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases

Grant support

The work (Project no. 2011-16850) was supported by Medical Innovation Fund of Indian Council of Medical Research, New Delhi, India (www.icmr.nic.in/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.