Self-DNA Sensing Fuels HIV-1-Associated Inflammation

Abstract

Inflammation, over-reacting innate immunity, and CD4⁺ T cell depletion are hallmarks of HIV-1 infection. Self-DNA is usually not considered in the context of HIV-1-associated inflammation, although self-DNA contributes to inflammation in diverse pathologies, including autoimmune diseases, cancer, multiorgan failure after trauma, and even virus infections. Cells undergoing HIV-1-associated pyroptotic bystander cell death release self-DNA and other damage-associated molecular patterns (DAMPs), including chaperones and histones. In complexes with such DAMPs or extracellular vesicles, self-DNA gains immunogenic potential and becomes accessible to intracellular DNA sensors. Therefore, we hypothesize that self-DNA can contribute to HIV-1-associated inflammation. Self-DNA might not only drive HIV-1-associated 'inflamm-ageing' but also provide new opportunities for 'shock and kill' strategies aimed at eliminating latent HIV-1.

Keywords: HIV-1; damage-associated molecular patterns; danger signals; inflammation; innate immunity; nucleic acid sensing.