Final Report Summary - HIV INNATE IMMUNITY (Toward an HIV-1 vaccine:<br/>Molecular mechanisms regulating the cryptic innate immune response to HIV-1)
We have found that DC infection results in induction of an innate response, which required the interaction between a viral protein, the Capsid, and a cellular protein, Cyclophilin A. Engaging this response leads to production of type I interferon, activation of adaptive immunity and blocking of T cell infection by the virus. We hypothesized that the innate response, which is cryptic because normally absent without efficient infection of DCs, is a factor that determines the ability of the immune system to control HIV infection. Based on these results, we aim at understanding how the interaction between Capsid and Cyclophilin A is connected to the cellular machinery that controls innate immune responses.
During the course of the project, we have identified a mechanism by which HIV-1 can be sensed. We were able to dissociate viral sensing from viral infection in dendritic cells. Doing so, we obtained a modified virus that allowed us to determine the viral determinants of sensing by dendritic cells. We have identified that the viral cDNA is essential for sensing and that in the cell, the innate sensor cGAS is required for detecting HIV-1. This work has been published in the journal Immunity. In addition to this, we have identified a novel regulator of HIV sensing in DCs. We are currently studying how this factor function in dendritic cells. Importantly these results inform us on how the innate immune system might sense HIV, and how the virus escapes this sensing.