The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells

Immunity. 2013 Dec 12;39(6):1132-42. doi: 10.1016/j.immuni.2013.11.002. Epub 2013 Nov 21.

Abstract

HIV-2 is less pathogenic for humans than HIV-1 and might provide partial cross-protection from HIV-1-induced pathology. Although both viruses replicate in the T cells of infected patients, only HIV-2 replicates efficiently in dendritic cells (DCs) and activates innate immune pathways. How HIV is sensed in DC is unknown. Capsid-mutated HIV-2 revealed that sensing by the host requires viral cDNA synthesis, but not nuclear entry or genome integration. The HIV-1 capsid prevented viral cDNA sensing up to integration, allowing the virus to escape innate recognition. In contrast, DCs sensed capsid-mutated HIV-1 and enhanced stimulation of T cells in the absence of productive infection. Finally, we found that DC sensing of HIV-1 and HIV-2 required the DNA sensor cGAS. Thus, the HIV capsid is a determinant of innate sensing of the viral cDNA by cGAS in dendritic cells. This pathway might potentially be harnessed to develop effective vaccines against HIV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid / immunology*
  • Cells, Cultured
  • DNA, Complementary / metabolism*
  • DNA, Viral / metabolism
  • Dendritic Cells* / immunology
  • Dendritic Cells* / virology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / metabolism
  • HIV-2 / genetics
  • HIV-2 / immunology*
  • HIV-2 / metabolism
  • Humans
  • Immunity, Innate / physiology
  • Models, Biological
  • Nucleotidyltransferases / metabolism*

Substances

  • DNA, Complementary
  • DNA, Viral
  • MB21D1 protein, human
  • Nucleotidyltransferases