Researchers look for drugs to keep HIV dormant

Researchers during a recent study found a way to look for chemicals that can keep the virus

suppressed into its dormant state.

 

The human immunodeficiency virus infects the cells that can either exploit them to start

making more copies of itself or remain dormant, a phenomenon called latency. Researchers

during a recent study found a way to look for chemicals that can keep the virus suppressed

into its dormant state.

 

The findings of the study were published in a new paper, Proceedings of the National

Academy of Sciences. "The current drug treatments block healthy cells from becoming

infected by the virus," said Yiyang Lu, a PhD student in the Dar lab at the University of

Illinois Urbana-Champaign. "The latent reservoir poses a bigger problem because it can start

producing the virus at any time. Consequently, patients have to remain on antiretroviral

therapy all their lives to prevent a viral rebound."

 

So far, there are two types of drug treatment strategies: shock-and-kill, where reactivated

cells are killed due to HIV, and a second drug cocktail prevents other cells from being

infected, or block-and-lock, which forces the virus into a deep latent state so that it does not

reactivate again. The problem with the first approach is that there are always some leftover

reservoirs that do not get activated. The problem with the second approach, which the

researchers are trying to solve, is that there aren't many drugs that have been discovered.

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Since the transition from latency occurs randomly, measuring the fluctuations in gene

expression can provide more coverage than the average gene expression. "Commercial drug

screens usually look at mean gene expression. Instead, we used a drug screen that looks at

fluctuations in gene expression. Our screen allowed us to therefore find more compounds that

could have been overlooked," Lu said.

 

"We implemented a time-series drug screening approach that are less commonly used in other

labs," said Roy Dar, an assistant professor of bioengineering at Illinois and faculty member of

the Carl R. Woese Institute for Genomic Biology. The researchers used a T- cell population,

which is a reservoir for HIV, that had been infected by the virus. They imaged the cells in 15-

minute intervals for 48 hours and tested over 1800 compounds. They looked at noise maps to

identify which drugs can modulate gene expression.

 

Using the screen, they were able to find five new latency-promoting chemicals, raising the

possibility that similar screens can be successfully adapted to study other systems that exhibit

variability in gene expression, such as cancer. They are currently working on understanding

how the five novel drugs suppress viral reactivation. "We want to test if these drugs have off target effects in terms of how many other genes they affect in the host cells," Dar said. "We

also want to test these drugs in patient samples to see whether these drugs suppress HIV in

them."

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