Purpose of review: The early stage of HIV-1 infection is when the virus is most vulnerable, and should therefore offer the best opportunity for therapeutic interventions. This review addresses the recent progress in the understanding of innate immune responses against HIV-1 with focus on the potential targets for prevention of viral acquisition, replication and dissemination.
Recent findings: Research indicates that the host-derived factor trappin-2/elafin is protective against HIV, whereas semen-derived enhancer of viral infection and defensins 5 and 6 enhance viral transmission. Further, studies suggest that stimulation of TLR4 and inhibition of TLR7-9 pathways may be HIV suppressive. The regulation and function of viral restriction factors tetherin and APOBEC3G have been investigated and a molecule mimicking the premature uncoating achieved by TRIM5α, PF74, has been identified. Chloroquine has been shown to inhibit plasmacytoid dendritic cell activation and suppress negative modulators of T-cell responses. Blockade of HMBG1 has been found to restore natural-killer-cell-mediated killing of infected dendritic cells, normally suppressed by HIV-1. Interestingly, when used as adjuvants, EAT-2 and heat shock protein gp96 reportedly enhance innate immune responses.
Summary: Several targets for innate immunity-mediated therapeutics have been identified. Nonetheless, more research is required to unveil their underlying mechanisms and interactions before testing these molecules in clinical trials.