MAVS Genetic Variation Is Associated with Decreased HIV-1 Replication In Vitro and Reduced CD4+ T Cell Infection in HIV-1-Infected Individuals

Viruses. 2020 Jul 16;12(7):764. doi: 10.3390/v12070764.

Abstract

The mitochondrial antiviral protein MAVS is a key player in the induction of antiviral responses; however, human immunodeficiency virus 1 (HIV-1) is able to suppress these responses. Two linked single nucleotide polymorphisms (SNPs) in the MAVS gene render MAVS insensitive to HIV-1-dependent suppression, and have been shown to be associated with a lower viral load at set point and delayed increase of viral load during disease progression. Here, we studied the underlying mechanisms involved in the control of viral replication in individuals homozygous for this MAVS genotype. We observed that individuals with the MAVS minor genotype had more stable total CD4+ T cell counts during a 7-year follow up and had lower cell-associated proviral DNA loads. Genetic variation in MAVS did not affect immune activation levels; however, a significantly lower percentage of naïve CD4+ but not CD8+ T cells was observed in the MAVS minor genotype. In vitro HIV-1 infection of peripheral blood mononuclear cells (PBMCs) from healthy donors with the MAVS minor genotype resulted in decreased viral replication. Although the precise underlying mechanism remains unclear, our data suggest that the protective effect of the MAVS minor genotype may be exerted by the initiation of local innate responses affecting viral replication and CD4+ T cell susceptibility.

Keywords: HIV-1 replication; MAVS genetic variation; T cell-induced immunity; antiviral immunity; human immunodeficiency virus 1; immune activation; viral load; viral sensing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Cytokines / metabolism
  • DNA, Viral / genetics
  • Gene Expression Regulation, Viral
  • Genetic Variation / genetics
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / physiology*
  • Humans
  • Viral Load / genetics
  • Virus Replication / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • DNA, Viral
  • MAVS protein, human