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Host Laboratory : Charlotte Charpentier ( ; IAME, Paris)
Dr Francesca Di Nunzio, Virology Department, Institut Pasteur : The Next Frontier: Breakthroughs in HIV Post-Nuclear Entry Research
HIV integration takes place at chromatin sites that facilitate the release of a high level of viral progeny. Alternatively, the virus can also exist discreetly within the host. To integrate into the host cell’s genome, HIV must reverse transcribe its genetic material from RNA to DNA. Notably, the viral genome is enclosed within the capsid shell, which recent research has shown to persist after viral fusion with the cellular membrane. This capsid shell acts as a shuttle to assist the virus in navigating into the host cell.
Traditionally, textbooks have indicated that the uncoating (loss of the viral capsid) and the reverse transcription processes occur exclusively within the host cytoplasm. However, recent discoveries, including our own, have revealed that these steps take place within the nuclear compartment of the infected cell. This post-nuclear entry step is associated with the remodeling of the nuclear landscape. Intriguingly, HIV-1 exploits a recently discovered biological phenomenon called liquid-liquid phase separation (LLPS) to efficiently undergo nuclear reverse transcription and integrate into neighboring active chromatin. Further details on this phenomenon will be discussed.
Pr Jade Ghosn, Service des Maladies infectieuses et tropicales, Hôpital Bichat-Claude Bernard, INSERM UMR 1137, IAME, Université Paris Cité :
Clinical use of the first capsid inhibitor, long-acting, Lenacapavir in therapeutic and in prevention
Capsid inhibitor is the most recent ARV new drug class, innovative regarding its potency and multistep inhibitory activity as well regarding its long-acting administration form. Safety and efficacy of this drug have been assessed in two phase 3 randomized trials that have included different profiles of persons living with HIV
Dr Quentin Le Hingrat, Service de Virologie, Hôpital Bichat-Claude Bernard, INSERM UMR 1137, IAME, Université Paris Cité : Genotypic and phenotypic determinants of HIV-2 resistance to Lenacapavir
In this webinar, we will focus on capsid inhibitors, from the perspective of the clinical virologist. This new class is promising, particularly as it unlocks the possibility of extremely long-acting regimens, but drug resistance-associated mutations in the capsid region have recently been described. We will discuss the implications of these mutations, from the reduced susceptibility to capsid inhibitors to the major impact they can have on viral fitness and the potential changes in the viral reservoir.

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