Interaction between endogenous bacterial flora and latent HIV infection

Abstract

Human commensal bacteria do not normally cause any diseases. However, in certain pathological conditions, they exhibit a number of curious behaviors. In HIV infection, these bacteria exhibit bidirectional relationships: whereas they cause opportunistic infections based on immunological deterioration, they also augment HIV replication, in particular, viral replication from latently infected cells, which is attributable to the effect of butyric acid produced by certain anaerobic bacteria by modifying the state of chromatin. Here, we review recent evidence supporting the contributory role of such endogenous microbes in disrupting HIV latency and its potential link to the clinical progression of AIDS.

Fig 1

Causal association of microbial interaction with HIV-1 latency and AIDS progression. HIV-1 infection weakens the immune system, making the body susceptible to opportunistic pathogens. CD4⁺ T cell depletion leads to impaired mucosal epithelial barrier integrity, allowing microbial translocation. The influx of circulating microbial products is associated with a systemic hyperimmune activation (e.g., through the TLR–NF-κB pathway) that may aggravate HIV-1 disease and enhance its progression. Recently, the bacterial metabolite butyric acid, which is produced under anaerobic conditions, has been shown to reactivate latent HIV-1 by promoting dissociation of the HDAC1–AP-4 repressor complex and hyperacetylation of histones, indicating its potential involvement in the progression of AIDS (see text for details). HATs, histone acetyltransferases; Me, methyl; Ac, acetyl; LPS, lipopolysaccharide.