HIV-infected individuals must receive lifelong antiviral therapy because treatment discontinuation generally results in rapid viral rebound. The field has identified a state of latency at the level of transcription of the integrated provirus as the major mechanism of persistence. A number of drugs are now tested that aim at inducing viral transcription as a step to purge the reservoir. The assessment of viral production in cells from HIV-infected individuals with optimal viral suppression revealed the failure of SAHA/vorinostat to efficiently generate viral particle production. To further investigate and characterize the process of latency at the transcriptome level, and the response to SAHA as well as various reactivating agents, we use a model of primary CD4+ lymphocytes. The main observation from this study is that viral transcripts persist during latency, and that the accumulation of viral transcripts does not result in efficient viral protein expression upon reactivation with agents such as SAHA. Our data suggest that post-transcriptional blocks also contribute to latency, and that additional strategies need to be explored to efficiently purge the viral reservoir.
Vyšlo v časopise: Dynamics of HIV Latency and Reactivation in a Primary CD4+ T Cell Model. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004156 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004156
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