The eradication of HIV faces a major obstacle, which is viral persistence in reservoir cells despite antiretroviral treatment. HIV latency refers to silent viruses that can still produce infectious particles if the treatment is interrupted. This can be explained by an inhibition of viral transcription and/or defects in co- or post-transcriptional steps. Our research group has demonstrated that HUSH suppresses the HIV-1 LTR promoter in several HIV-1 latency models, suggesting that HUSH may play a role in HIV latency (Chougui et al., 2018)(Matkovic et al., 2022).

 

 

Members of the project

Collaborations

Internal:
Florence MARGOTTIN-GOGUET
Véronique AVETTAND-FENOEL

Local:
-Stéphane EMILIANI - Institut Cochin

National:
-Gael CRISTOFARI - IRCAN Nice

International:
-Maike HANSEN - Radbud University - NED

Our work

Recently, The group of Roy Matkovic discovered a new mechanism of gene silencing in human cells that connects epigenetic silencing and RNA degradation: HUSH interacts with CNOT1, the nuclear RNA exosome, to induce degradation of RNA transcription from the HIV-1 LTR, while also promoting heterochromatinization of the provirus through H3K9me3 propagation (Matkovic et al, Nature Communications 2022). This novel type of gene expression repression mechanism in mammals demonstrates a close link between RNA metabolism and transcriptional gene repression.

The research group led by Roy MATKOVIC aims to understand, using biochemical, genetic, epigenetic, and molecular approaches, the interplay between the HIV-1 genomic RNA, Long non coding RNAs in building macromolecular complexes to prevent HIV-1 expression, leading to latency.

Publications

TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV.
Matkovic R✉, Morel M, Lanciano S, Larrous P, Martin B, Bejjani F, Vauthier V, Hansen MMK, Emiliani S, Cristofari G, Gallois-Montbrun S, Margottin-Goguet F✉.
Nat Commun. 2022 Jan 10;13(1):66. doi: 10.1038/s41467-021-27650-5. (✉: co-corresponding)

Link to Article

HUSH-mediated HIV silencing is independent of TASOR phosphorylation on threonine 819.
Vauthier V, Lasserre A, Morel M, Versapuech M, Berlioz-Torrent C, Zamborlini A, Margottin-Goguet F✉, Matkovic R✉. Retrovirology. 2022 Oct 29;19(1):23. doi: 10.1186/s12977-022-00610-7 (✉ : co-corresponding)

Link to Article

Binding to DCAF1 distinguishes TASOR and SAMHD1 degradation by HIV-2 Vpx.
Martin MM*, Matkovic R*, Larrous P, Morel M, Lasserre A, Vauthier V, Margottin-Goguet F. PLoS Pathogens 2021 Oct 26;17(10):e1009609. doi: 10.1371/journal.ppat.1009609. (*: co-first)

Link to Article

HIV-2/SIV viral protein X counteracts HUSH repressor complex.
Chougui G, Munir-Matloob S, Matkovic R, Martin MM, Morel M, Lahouassa H, Leduc M, Ramirez BC, Etienne L, Margottin-Goguet FNat Microbiol. 2018 Aug;3(8):891-897. doi: 10.1038/s41564-018-0179-6. 

Link to Article