Long non-coding RNAs in HIV latency: a new approach for improved latency reversal in shock-and-kill cure strategies.
HIV is a virus that attacks the human immune system. Current medication can prevent a patient from getting AIDS when infected with HIV, but it cannot completely cure the patient, as a small part of the virus population is in a sort of U+2018sleepingU+2019 state that cannot be targeted by the drugs. The virus manipulates the machinery of the infected cell in a lot of different ways to stay in this undetectable state. One of these ways is the misuse of a special type of human long gene transcript that does not code for any protein. Instead, these gene transcripts, called lncRNAs, have a functionality of their own. This project aims to identify the lncRNAs (and their interactions) contributing to HIV latency, so that their function can be counteracted by a drug. Hence, drugs targeting these lncRNAs themselves or blocking their interactions could reactivate the virus to make it susceptible for clearance by the immune system, or could improve the efficacy of current latency reversing agents. First, the lncRNA interaction partners of three HIV proteins involved in latency maintenance will be determined. Thereafter, these lncRNAs and preliminary discovered lncRNAs possibly contributing to latency maintenance, will be validated by performing lncRNA knockdown experiments, both in a cell model (J-Lat), as in patient derived cells. This can have a substantial contribution to HIV cure strategies, ultimately reducing the one million casualties the virus makes every year.