A major obstacle to the eradication of HIV is the persistence of the virus in the reservoir cells despite antiretroviral therapy. HIV latency refers to silent viruses, which can still produce infectious particles if treatment is interrupted. It can be explained by an inhibition of viral transcription and/or by a defect in post-transcriptional steps. Our group has shown that HUSH represses the HIV-1 LTR promoter in several models of HIV-1 latency and has therefore proposed that HUSH may be a player in HIV latency.

We have recently discovered a novel mechanism of gene silencing in human cells that links epigenetic silencing and RNA degradation: HUSH interacts with CNOT1, the nuclear RNA exosome to induce degradation of RNA transcription transcribed from the HIV-1 LTR, while HUSH does is also responsible for the HIV-1 provirus heterochromatinization through propagation of H3K9me3 (Matkovic et al, Nature Communications 2022).

We aim to understand how HIV-1 genomic RNA and the associated host cell macromolecular complexes prevent HIV-1 expression and lead to latency.