Séminaire CIRI: Francesca DI NUNZIO
Date / Heure
Date(s) - 20/02/2020
10 h 00 min - 11 h 00 min
salle des Thèses Chantal Rabourdin-Combes
Francesca DI NUNZIO (Institut Pasteur Paris): « On the road to the nucleus of HIV-1 natural target cells »
Retroviral replication proceeds through obligate integration of the viral DNA in the nucleus, essential for efficient viral gene expression. However, to be able to integrate into the host genome, the viral DNA must be led through the nuclear pore complex. Therefore, the morphology of the CA protein associated to the functional PIC during its translocation is completely unknown. We are currently studying early steps of viral life cycle in dividing and non-dividing cells, both target cells of HIV-1. Using breakthrough imaging technologies we deciphered the morphology adopted by HIV-1 during the translocation into the host nucleus of CD4+T cells. This step of the HIV-1 life cycle has never been previously elucidated because of the lack of appropriate technologies. Along with activated CD4+ T cells, macrophages are also natural target cells for HIV-1 and accumulating evidence points to a critical role of these cells in viral persistence, which remains a major roadblock to a cure for AIDS. Yet, it is not known whether the replication cycle proceeds differently in other cell types, such as non-dividing cells. Indeed, different cell types can exhibit widely divergent responses to viral attacks. Macrophages are terminally differentiated, non-dividing cells derived from blood monocytes, which play a critical role in the innate and adaptive immune response. Surprisingly, we detected in the nucleus of human macrophages viral RNA foci composed mostly of genomic, incoming RNA, which are niches of viral life cycle functions. These findings change our view of the spatiotemporal events of the early HIV-1 replication cycle in macrophages and may contribute to understand the mechanism underlying the persistence of HIV-1.
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