CVM researchers awarded NIH grant to study a microscopic compound with a major impact on viral replication

A research team led by Kathleen Boris-Lawrie, Professor in the Department of Veterinary and Biomedical Sciences, received $572,000 from the National Institutes of Health to study and characterize genetic features of the HIV virus that are linked to its replication. A better understanding of these features will pave the way for new targets for the development of antiviral therapies against retroviruses.

Because viruses can’t replicate their own genes, they must invade cells and hijack their hosts’ machinery to replicate. In the HIV virus, a particular compound called Guanosine plays a significant role in the virus’s ability to proliferate—by 1000-fold—but the process by which it does so is poorly understood. Preliminary research suggests that a new type of anti-inflammatory drug, ABX464, sabotages the action of the virus’s Guanosine, but like the beneficial effects of Guanosine itself, the mechanisms of how the drug works remain unclear.

RNA with methyl Guanosine (left) and without (right)

With this NIH funding, the team will conduct experiments using the tools of molecular virology and structural biology to characterize the complex interactions between the virus RNA and its host’s proteins, as well as the characteristics of the virus itself, that allow Guanosine to promote the virus’s replication. By developing a better understanding of these relationships and processes, the proposed studies are expected to pave the way for the development of new antiviral therapies that, like ABX464, target these previously mysterious pathways in many types of viruses and their hosts. 

"We are excited to build on our recent discovery that the microscopic Guanosine methylation boosts the proliferation of canine sarcomas, as well as the immunodeficiency virus,” says Boris-Lawrie. By targeting the Guanosine, a common denominator between these disease states, we uncovered a specialized pathway used by cells under stress. Instead of thriving under stress, lack of Guanosine methylation halts resilience and opens the alternative road to cell death.  Thus, this research is ultimately important to program resilience or death to diseased cells.” In other words, the research will give us a broader understanding about cell health and disease, and how to design therapies that promote or terminate resilience in cells.