Although we now have an antiviral treatment, there is still no cure for HIV/AIDS. Lack of access and the high cost of lifelong treatment remain significant obstacles for millions of people globally. And even those who do get treatment face shortened lifespans. At the Ott Lab, our HIV research is focused on cure, and our goal is to eradicate the virus.
To replicate, the virus that causes HIV/AIDS inserts copies of its genome into the host cell and hijacks the transcription machinery. Our work helped define the critical role of the viral transactivator Tat in this process, especially how Tat is modified by host enzymes during infection. In addition, we focus on host factors that control the chromatin landscape of the HIV provirus in order to find new latency-controlling drugs.
HIV infection continues to shorten the lives of people living with the virus. Our work has shown that the virus directly manipulates the biology of aging via the deacetylase SIRT1 and its downstream target FOXO1. Using organoid technology, we are now exploring how chronic inflammation destroys stem cell and epithelial barrier functions in the gut.
HIV uses the host RNA polymerase to transcribe its genome. The polymerase complex continuously occupies the beginning of the HIV genome in a “paused” state. Ongoing work identified eight lysine residues in the polymerase that –by reversible addition or removal of acetyl groups– regulate the pausing at the HIV genome and other genes in humans.
Individuals living with HIV need to monitor their viral load carefully, which entails frequent visits to a lab. However, the majority of new HIV infection occurs in third-world countries, where transportation and access to labs is often limited. Together with Drs. Jennifer Doudna and Dan Fletcher of UC Berkeley, we develop a CRISPR-based testing platform that uses a mobile phone camera to read the test results, delivers quantitative results within 5 to 30 min, and does not need to be carried out in a lab. See how this new diagnostic can also be used for SARS Co-V-2 and influenza.
