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  • Visiting Scientist
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  • Director of Center
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© Research
Laboratory

Advanced Molecular Virology

Department of Virology

Scientific Fields
Diseases
Organisms
Applications
Technique

About

HIV was discovered in 1983 and the reverse transcription (RT) process that characterizes all retroviruses in 1970. However, new notions on the RT were deciphered only recently.

Of note, our group has played a major role in revealing new spatiotemporal aspects of RT, uncoating (loss of the viral capsid shell) and the topology of HIV pre-integration, maturation and integration. Inside the host nucleus, newly synthesized viral DNA (vDNA) was found in HIV-1-induced cleavage and polyadenylation specific factor 6 (CPSF6) / serine/arginine-rich splicing factor (SC35) organelles. We called these viral/host structures HIV-1 membraneless organelles (HIV-1 MLOs). The aim of our research is untangling the mechanism underlying HIV-1 MLO biogenesis and their role in viral retrotranscription, replication and latency.

We propose a bipartite model of HIV post-nuclear entry steps:

Next steps include in vivo studies.

In particular, we aim at elucidating mechanism/s in common among divergent viruses that interact with host components inside MLOs and sabotage cellular compartments to their advantage.

MLOs induced by HIV-1 and SARS-CoV-2 to replicate from Scoca & Di Nunzio JMCB 2021. Left: HIV-1 infection prompts the formation of nuclear MLOs enriched with host factors, such as CPSF6 and SC35, and in viral components, such as vRNA, vDNA, capsid, and integrase. Right: SARS-CoV-2 N protein forms condensates in the cytoplasm to recruit exclusively intact vRNA genome against subgenomic vRNAs or host RNAs . Cartoon created with BioRender.com.

 

 

 

Former Members

2000
2000
Name
Position
2016
2019
Guillermo Blanco-Rodriguez
PhD student
2017
2019
Stella Frabetti
ERASMUS student / engineer Sidaction
2018
2020
Elena Rensen
post-doc
2021
2021
Clement de la Myre Mory
Master 2 student

Projects

Upon infection, HIV-1 can either replicate and acutely infect cells or remain dormant. Currently, we have no means of eradicating the latent virus from cells. The establishment of viral persistence could be an early event, probably linked to the active transport of the PIC through the NPC. The NPC is one of the major actors in the early steps of HIV-1 infection. Notably, Nups have pleiotropic roles, in fact they interact with different protein complexes involved in gene transcription, chromatin remodelling, DNA repair, and DNA replication. Past and current studies from our group highlighted the importance of the interplay between individual nucleoporins and the viral capsid for HIV-1 nuclear entry and for an efficient viral integration. Ultrastructural studies revealed that the viral core remodels to cross the nuclear pore complex. On the other hand, the HIV-1 retrotranscribed DNA has never been visualized in live, hampering studies on the spatiotemporal dynamics linked to viral silencing or activation. In fact, the direct detection of HIV-1 genomes after reverse transcription has been a technological challenge to study HIV-1 PIC morphogenesis, as well as viral integration sites distribution. We recently set up in our lab a new appealing versatile fluorescence system, called HIV-1 ANCHOR, to overcome the aforementioned limitations to study the host environment (chromatin and nuclear factors) surrounding nuclear viral forms that can dictate viral transcription or silencing. We generated a HIV-1 WT that can be labeled for both viral DNA and viral RNA in live. This system can be used in primary lymphocytes or macrophages allowing to perform studies on the main target cells of HIV-1. Our new tool will allow to follow the fate of HIV-1 in the natural target cells.

Results from our group indicate that HIV-1 creates nuclear microenvironments to replicate. Post-nuclear entry studies showed the existence of a nuclear reverse transcription (RT), revising the RT “dogma”. This viral step occurs in HIV-1-induced-membraneless organelles. Our future studies will shed light on this intriguing phenomenon to unravel underlying molecular mechanisms (in vitro) and to evaluate their role in HIV reservoirs (in vivo).

Fundings

Publications

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Recent events

  • Article on Transversal from Sidaction:

https://transversalmag.fr/articles-vih-sida/1356-VIH-La-transcription-inverse-vue-sous-un-nouveau-jour

 

  • CROI 2021: Deciphering the host nucleus subversion by HIV-1 to replicate
    http://www.croiwebcasts.org/p/2021croi/croi/78

 

  • ANRS AC41 (host/viral interactions):

 

 

 

  • La chronique santé de Thierry Lhermitte (testimonial FRM):

    https://www.franceinter.fr/emissions/la-chronique-sante-de-thierry-lhermitte/la-chronique-sante-de-thierry-lhermitte-du-lundi-13-decembre-2021