A surprise discovery that could lead to new treatments for herpes viruses that infect more than 90 percent of the world's adult population has led to a $1.8 million grant to the University of Arkansas for Medical Sciences (UAMS) from the National Cancer Institute (NCI) at the National Institutes of Health (NIH).
UAMS researcher Craig Forrest, Ph.D., found that a certain protein may suppress the herpes virus and possibly several cancers that are caused by related herpes viruses.
"This protein really appears to put the brakes on the virus from the start," said Forrest, an assistant professor in the UAMS College of Medicine's Department of Microbiology and Immunology.
The five-year NCI grant will allow Forrest and collaborating researchers to use innovative genetics techniques to manipulate the herpes virus and its genes as they test the protein (p53), which is known for suppressing cancer.
He hopes that a more complete understanding of the protein's role in restricting the virus will someday lead to new treatments. While most people have a natural resistance to cancers caused by the herpes virus, treatments could be lifesaving for those with weakened immune systems, including organ transplant patients, HIV/AIDS patients, and cancer patients undergoing chemotherapy.
"For people who have compromised immune systems, herpes viruses like the Epstein-Barr virus have a nasty habit of coming back as different diseases like lymphoma and other cancers," Forrest said.
The Epstein-Barr virus, which is in the family of herpes viruses that Forrest is studying, infects more than 90 percent of the adult population, but most people will never develop a cancer caused by the virus.
"We have a technique by which we can allow the virus to set up shop and then knock out viral genes," he said. "We propose doing the same thing with the p53 protein. We can delete p53 and then ask what happens in terms of the chronic viral infection: Do you increase or decrease viral loads? Do you increase cancer incidence? We predict that you would, but we don't know for sure."
Forrest, a Jonesboro native, joined UAMS in 2009 after completing postdoctoral research at Emory University in Atlanta. His discovery of the important role of the p53 protein was made while testing various signaling proteins in the genomes of mice.
Forrest's early research was funded by the Arkansas BioSciences Institute, supported by Arkansas' share of a national tobacco industry settlement, and the NIH-funded Center of Biomedical Research Excellence (COBRE) at UAMS, and a pilot study funded by the UAMS Translational Research Institute.
"We got some very unique data from the pilot study that led us to test the function of p53 in chronic herpes virus infection," Forrest said. "We found that the p53 protein is restricting the virus from establishing a chronic infection. If you deleted p53 from the mouse genome, you got a really big increase in the number of infected cells."
Forrest's grant application to the NCI earned a perfect score of 10 from reviewers, who anticipate that his research "may reveal novel therapeutic targets," and concluded, "In sum, there is considerable enthusiasm for the talented new investigator (Forrest) and the proposed work …."
"It was exciting to see the reviewers' scores, and much of the credit goes to some key collaborating researchers at UAMS and my hard-working lab group," Forrest said. "They are directly responsible for the preliminary data that made the grant successful."