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Project: ASP-L, An antisense HIV RNA transcript that acts in HIV latency

project duration
01/01/14 – 31/12/14
abstract
The introduction of antiretroviral therapy directed against the human immunodeficiency virus (HIV) resulted in a asuppression of disease progression, effectively limiting the incidence of infected patients developing the acquired immunodeficiency syndrome (AIDS). This led to a major decrease in AIDS related mortality. However, current therapies are still unable to cure HIV infected patients, since a small reservoir of replication competent but latent proviral HIV DNA persists despite long term therapy. The mechanisms of viral latency are under extensive investigation in an attempt to develop a cure to purge the latent HIV reservoir. Multiple molecular factors have been described that influence HIV latency, but one particular family, i.e. non-coding RNAs has remained largerly unstudied. Non-coding RNAs (ncRNAs) have only been recently discovered, but current data already hints that these RNA forms are crucial in mulitple cellular pathways. Recently, a viral derived ncRNA was described that inhibits viral replication, suggesting that this factor may play a role in HIV latency. In the present project, the effect of this viral ncRNA on HIV latency will be assessed using cell culture experiments optimized to mimic HIV latency. The expression rates of this factor will be assessed and the effect of a targeted knock down of its expression will be assessed in the models. In addition, the molecules binding to this transcript will be identified to assess how the ncRNA affects HIV latency.