Broadly neutralizing antibody VRC01 prevents HIV-1 transmission from plasmacytoid dendritic cells to CD4 T lymphocytes

J Virol. 2014 Sep;88(18):10975-81. doi: 10.1128/JVI.01748-14. Epub 2014 Jun 25.

Abstract

Plasmacytoid dendritic cells (pDC) poorly replicate human immunodeficiency virus type 1 (HIV-1) but efficiently transfer HIV-1 to adjacent CD4 T lymphocytes. We found that coculture with T lymphocytes downregulates SAMHD1 expression, enhances HIV-1 replication, and increases pDC maturation and alpha interferon (IFN-α) secretion. HIV-1 transfer to T lymphocytes is inhibited by broadly neutralizing antibody VRC01 with efficiency similar to that of cell-free infection of T lymphocytes. Interestingly, prevention of HIV-1 transmission by VRC01 retains IFN-α secretion. These results emphasize the multiple functions of VRC01 in protection against HIV-1 acquisition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Neutralizing / pharmacology*
  • Antibodies, Viral / pharmacology*
  • Broadly Neutralizing Antibodies
  • CD4-Positive T-Lymphocytes / virology*
  • Cells, Cultured
  • Dendritic Cells / virology*
  • HIV Antibodies / pharmacology*
  • HIV Infections / prevention & control
  • HIV Infections / virology*
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • Humans

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Broadly Neutralizing Antibodies
  • HIV Antibodies
  • VRC01 monoclonal antibody