Grant: Operating Grant

The presence of latently infected cells has precluded any hope to find a cure for HIV-1 for many years. Although latently infected resting memory CD4+ T cells constitute the major HIV-1 reservoir, other sites of viral persistence must be considered in eradication strategies. The central nervous system (CNS) constitutes one of these important and stable reservoirs, and its purge could be the most challenging issues in the next few years. The primary goals of the current research project are to better understand how latency is established in some resident cells of the CNS (i.e. astrocytes and microglial cells), and what are the consequences of purging strategies on this HIV-1 reservoir. We will study the mechanisms by which brain astrocytes get infected by HIV-1. In addition we will clarify whether microglial cells can serve as a latent reservoir. Lastly, we will analyse the consequences of therapeutics used for HIV-1 reactivation on latently infected astrocytes and microglial cells. The risks associated with HIV-1 eradicating strategies include increased brain infection, neurological damages through production of neurotoxic viral proteins and immune-related injuries such as encephalitis. Hence, better understanding of the mechanisms of HIV-1 latency in the brain is urgently needed.