NCI Funds UAMS Study of Possible Links between Gammaherpesvirus Infections and Lymphomas

By Seth Hooker

The five-year, $1.25 million grant renewal will mostly support ongoing work to better understand how gammaherpesvirus promotes mutations (chromosomal translocations) that lead to lymphomas. In addition, the grant will allow UAMS’ Craig Forrest, Ph.D., to study the possible link between combined malaria and gammaherpesvirus infections in the development of lymphoma.

“This is one of those big questions that’s been around for over 50 years,” said Forrest, a professor in the UAMS College of Medicine Department of Microbiology and Immunology. “We hope to learn more about how malaria parasites and the virus may work together to cause cancer.”

The funding will also help further Forrest’s work on earlier discoveries related to the tumor-suppressor protein, p53. The protein, his lab found, is critical for preventing chronic infection from gammaherpesviruses.

“This grant renewal represents an opportunity for us to continue studying how herpesviruses cause disease,” Forrest said.

In addition to providing a better understanding of how gammaherpesviruses cause disease, Forrest anticipates that results of this work will inform new therapeutic approaches for lymphoma and the reduction of mutations caused by gammaherpesviruses and related co-infections such as malaria-causing parasites.

His lab has focused on synthetic viruses, introduced to mice subjects, that mimic Epstein Barr virus (EBV) proteins. EBV infects more than 95% of the adult population and causes infectious mononucleosis and several cancers. After becoming infected, the virus becomes dormant in the body, although it can reactivate and cause cancer in susceptible individuals. There is no vaccine for humans against gammaherpesviruses.

In the next five years, Forrest expects his research to yield answers to questions such as:

  • How do gammaherpesviruses promote tumor growth?
  • What cellular factors are responsible for the types of cancer that develop?
  • How does malaria co-infection with a gammaherpesvirus influence Burkitt lymphoma development?

Forrest credited his colleagues’ hard work and creativity in generating his lab’s findings and securing the NCI grant. “None of this would be possible without my team,” he said, mentioning Shana Owens, Ph.D.; Jeff Sifford, Ph.D.; Gang Li, Ph.D.; and Jason Stumhofer, Ph.D.

This research is supported by the National Institutes of Health NCI grant R01 CA167065-06A1.