The Relevance of Post-Transcriptional Mechanisms in HIV Latency Reversal.

BACKGROUND: Infection by the human immunodeficiency virus has become a treatable disease, which could not be cured because the virus persists in the face of an efficacious drug treatment. Current efforts for the rescue of replication-competent virus from cellular reservoirs are limited to drugs targeting transcriptional reactivation of the dormant virus and clinical trials so far are disappointing. One explanation could be that posttranscriptional pathways are not optimal thus impeding full reactivation of the virus, which is required for purging the cellular reservoirs.

OBJECTIVE: This review is focused on the post-transcriptional pathways of viral RNA processing. In this review, the complex regulation of viral RNAs in the nucleus, their export to the cytoplasm and engagement in translation and packaging are discussed in the context of reactivation and latency. In addition, post-transcriptional regulation of viral and cellular gene expression, by RNA interference, is considered with respect to HIV-1 reactivation from latency.

CONCLUSION: Complete rescue of virus from the cellular reservoir is likely to require a combination of drugs targeting transcriptional and post-transcriptional pathways carefully tailored to HIV-1.