Journal of virology 2017 05 24() pii 10.1128/JVI.01943-16
In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4(+) T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4(+) T cells upon acetate treatment. This enhancing effect correlates with an increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration in the genome of CD4(+) T cells. Thus, we propose that upon antigen presentation, acetate influences class I/II HDAC activity that transforms condensed chromatin into a more relaxed structure. This event leads to a higher level of viral integration and an enhanced HIV-1 production. In line with previous studies showing reactivation of latent HIV-1 by SCFAs, we provide evidence herein that acetate can also increase susceptibility of primary human CD4(+) T cells to productive HIV-1 infection.IMPORTANCE Alterations in the fecal microbiota and intestinal epithelial damages involved in the gastrointestinal disorder associated with HIV-1 infection result in microbial translocation that leads to disease progression and virus-related comorbidities. Indeed, notably via production of short-chain fatty acids (SCFAs), bacteria migrating from the lumen to the intestinal mucosa could influence HIV-1 replication by causing epigenetic regulatory mechanisms such as histone acetylation. We demonstrate that acetate enhances virus production in primary human CD4(+) T cells. Moreover, we report that acetate impairs class I/II histone deacetylase activity and increases integration of HIV-1 DNA into the host genome. Therefore, it can be postulated that bacterial metabolites such as acetate modulate HIV-1-mediated disease progression.