Abstract
Highly active antiretroviral therapy (HAART) has limited the replication and spread of the human immunodeficiency virus (HIV). However, despite treatment, HIV infection persists in latently infected reservoirs, and once therapy is interrupted, viral replication rebounds quickly. Extensive efforts are being directed at eliminating these cell reservoirs. This feat can be achieved by reactivating latent HIV while administering drugs that prevent new rounds of infection and allow the immune system to clear the virus. However, current approaches to HIV eradication have not been effective. Moreover, as HIV latency is multifactorial, the significance of each of its molecular mechanisms is still under debate. Among these, transcriptional repression as a result of reduced levels and activity of the positive transcription elongation factor b (P-TEFb: CDK9/cyclin T) plays a significant role. Therefore, increasing levels of P-TEFb expression and activity is an excellent strategy to stimulate viral gene expression. This review summarizes the multiple steps that cause HIV to enter into latency. It positions the interplay between transcriptionally active and inactive host transcriptional activators and their viral partner Tat as valid targets for the development of new strategies to reactivate latent viral gene expression and eradicate HIV.
Highlights
Since its discovery 30 years ago, the human immunodeficiency virus (HIV) has turned from a highly epidemic threat to a persistent pathogen that co-exists with its host. This progress is mainly due to the administration of effective highly active antiretroviral therapy (HAART) that targets key viral enzymes, which are essential for the replication of HIV [1]
Is required globally for optimal levels of S2 phosphorylation in the C-terminal domain (CTD) of RNA polymerase II (RNAPII). These findings demonstrate a vital role of capping protein binding complex (CBC) in connecting pre-mRNA capping to transcription elongation and alternate splicing via positive transcription elongation factor b (P-TEFb) [64,65,67]
The complex network that maintains HIV latency represents a major obstacle to the eradication of the virus
Summary
Since its discovery 30 years ago, the human immunodeficiency virus (HIV) has turned from a highly epidemic threat to a persistent pathogen that co-exists with its host This progress is mainly due to the administration of effective highly active antiretroviral therapy (HAART) that targets key viral enzymes, which are essential for the replication of HIV [1]. With the introduction of HAART, the spread of the virus has been substantially diminished and viral RNA levels can be reduced to clinically undetected levels in HIV-infected individuals [1]. Viral infected cell reservoirs that appear early in the infection accumulate in sites that resist eradication of the virus by the currently available antiretroviral therapies As these pools are highly stable, life-long HAART is required, which, in turn, causes severe side effects and promotes the evolution of viral-resistant strains [2]
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