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

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.

Genomic Evidence for the Nonpathogenic State in HIV-1–Infected Northern Pig-Tailed Macaques

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Connection Between HIV and Mitochondria in Cardiovascular Disease and Implications for Treatments

“…226 While HIV may suppress MAVS responses, single nucleotide polymorphisms in MAVS confer resistance to HIV-1-dependent suppression, thus reducing the progression of HIV. 227 Given the genetic association of single nucleotide polymorphisms, this suggests a potentially valuable new avenue to study how genetic background may confer different risks to HIV, which extend beyond geographic location and socioeconomic status.…”

Special Issue: “Innate Immune Sensing of Viruses and Viral Evasion”

“…Retroviruses, including the Human Immunodeficiency virus, are RNA viruses that reverse transcribe their RNA genome into DNA. Different aspects of RNA or DNA sensing in retroviral infections are highlighted in one review [5] and one original article [6] and a review on the distantly related endogenous retrotransposons [7]. The recognition of DNA viruses was enigmatic until the recent discovery of several DNA sensors.…”