New research on the structure of HIV has revealed new findings, showing that the virus’s genetic code can be read in two different ways by HIV-infected cells. The result is that infected cells make two different forms of the virus’s RNA.
“This functional diversity is essential for the virus to replicate in the body. The virus has to have a proper balance between the two forms of RNA,” says Joshua Brown, the lead author of the study. “For decades, the scientific community has known that two different structural forms of HIV RNA exist--they just didn't know what controls that balance. We've discovered that a single nucleotide is having a huge effect, which is a paradigm shift in understanding how HIV works.”
Crucially, “You can imagine that if you could come up with a drug that would target the genetic code at that one specific spot, and shift it to one form only, then it could prevent further infection, theoretically,” says Brown.
Issac Chaudry, a junior at UMBC and an author on the paper states that “One of the things we're working on now is testing different molecules that could shift the equilibrium between the two forms, so that it could potentially be used as a treatment for HIV.”
“Drug discovery isn't the direction that the Summers lab usually goes, but this was such an impactful finding in a very attractive area, we took the initiative to start looking into it,” Brown says of the research group led by Michael Summers, Robert E. Meyerhoff Chair for Excellence in Research and Mentoring and Distinguished University Professor at UMBC. “But we're still in the very early stages.”
This new research opens up a range of opportunities for Brown's research group and others. “We're very interested to see how other labs will interpret our results, expand upon them, and possibly find other applications for this type of RNA function,” Brown says.
Those future results and any new therapies they enable could have a major impact. “Every time we get a new drug in HIV, we exponentially improve the chances of individuals finding a drug that works for them, where resistance is a little less likely,” says Hannah Carter, M.D./Ph.D. student at University of Michigan, and an author on the paper. “Every time a new drug can get on the scene, that's a significant improvement for the lives of HIV patients.”
As ‘EurekAlert’ reports, the research could have effects beyond HIV, too. “Some HIV research has laid the groundwork in how we understand coronaviruses,” Carter adds. “All basic science in HIV ends up having a ripple effect throughout all of virology.”
The ripple effect might go even farther. “The idea that a single nucleotide difference is changing the structure and function of RNA that is thousands of nucleotides long could open up a whole new aspect of cell biology,” Chaudry says. “It could be possible that there are mammalian genes that operate in a similar manner, and the entire mechanism might be something that's applicable to other human genes as well. I think that whole paradigm could provide a new perspective for RNA biology.”
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