Preclinical shock strategies to reactivate latent HIV-1: an update.
The 'shock and kill' strategy consists of activating HIV-1 expression to allow latently infected cells to die from viral cytopathic effects or host cytolytic immune effectors. This strategy relies on small molecules, called latency reversing agents, which activate HIV transcription.



Several mechanisms operating at the transcriptional level are involved in the establishment and maintenance of HIV-1 latency, including the absence of crucial inducible host transcription factors, epigenetic silencing, and the sequestration of the positive transcription elongation factor B. Progresses made toward the understanding of the molecular mechanisms of HIV-1 transcriptional repression have led to the identification of latency reversing agents that activate HIV transcription, such as histone deacetylase inhibitors or protein kinase C agonists. Multiple studies have recently pointed interesting ways to optimize the shock strategy by using combinations of latency reversing agents with an appropriate time schedule.



Combining latency reversing agents appears as one potential strategy for therapy against HIV-1 latency.
aService of Molecular Virology, Département de Biologie Moléculaire (DBM), Université Libre de Bruxelles (ULB), Gosselies, BelgiumbService des Maladies Infectieuses, Université de Liège, Centre Hospitalier Universitaire (CHU) de Liège, Domaine Universitaire du Sart-Tilman, Liège, Belgium.
Gilles
G
Darcis
Benoît
B
Van Driessche
Carine
C
Van Lint
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000379:methods; D015658:HIV Infections / Q000628:therapy* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D014158:Transcription, Genetic / Q000187:drug effects; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency / Q000187:drug effects*
D000998:Antiviral Agents