Académie royale de Médecine de Belgique

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Résumé de Carine Van Lint

(Ont pris part à la discussion : MM. N. Clumeck, E. Pays, G. Casimir et J.-L. Vanherweghem)

(Séance du samedi 22 février 2014)

ÉTUDES DES MÉCANISMES MOLÉCULAIRES RÉGULANT LA LATENCE DU VIRUS HIV-1 (HUMAN IMMUNODEFICIENCY VIRUS TYPE 1) : IMPLICATIONS THÉRAPEUTIQUES

par Carine VAN LINT (ULB), invitée.                

Combination antiretroviral therapy (cART), despite being potent and life-prolonging, is not curative and does not eradicate HIV-1 infection since interruption of treatment inevitably leads to a rapid rebound of viremia. Reactivation of latently-infected cells harboring transcriptionally silent but replication-competent proviruses is a potential source of persistent residual viremia in cART-treated patients. Although multiple reservoirs may exist, the persistence of resting CD4+ T cells carrying a latent infection represents a major barrier to HIV-1 eradication. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In this talk, I will review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. I will also highlight the potential of recent pharmacological therapeutic strategies based on this understanding of latency and aimed at reactivating HIV-1 transcription in latently-infected cells, while maintaining cART in order to prevent de novo infection. Combinations of various compounds used simultan eously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well underway.