UAMS Receives $2.9M Grant to Study Virus That Can Trigger Cancers

Craig Forrest (File photo)

UAMS has received a five-year, $2.9 million research grant from the National Institutes of Health based on a discovery that a viral protein can help a cancer-associated herpesvirus evade the immune system.

Craig Forrest, a professor in the UAMS College of Medicine Department of Microbiology and Immunology, will use the grant to help reveal functions of the viral protein known as latency-associated nuclear antigen (LANA). The research is focused on LANA’s roles during infection by the gamma herpesvirus known as Kaposi sarcoma-associated herpesvirus (KSHV).

Kaposi sarcoma is a rare cancer caused by KSHV that affects the skin, lymph nodes and internal organs. Gamma herpesviruses, including KSHV, are known for establishing lifelong infections in their hosts. For most people, the viruses remain latent, only reactivating under certain conditions.

But KSHV is of particular concern because it is associated with several types of cancer, especially in people with compromised immune systems, such as those living with human immunodeficiency virus (HIV).

Forrest said in a press release that he hopes the work will help lead to a vaccine for Kaposi sarcoma and other cancers caused by gamma herpesviruses.

The grant came about when a Ph.D. student in Forrest’s lab, Steven Murdock Jr., found that the presence of LANA correlated with an almost nonexistent immune response against KSHV.

“First of all, it was great preliminary data to support the rationale for the NIH grant proposal,” Forrest, who has been studying gamma herpesviruses since 2003, said in the release. “But second of all, I thought, ‘That’s amazing, and now what can we do to figure out how the virus is preventing immune recognition?’”

At the end of the five-year grant, Forrest hopes to have figured out what mechanism LANA uses for preventing immune detection by the body. LANA helps maintain gamma herpesviruses in a latent state, allowing an infection to remain in the body without any symptoms. By understanding how LANA helps KSHV evade immune detection, Forrest aims to uncover new ways to prevent or treat KSHV-associated cancers.

“Our hypothesis is that the virus’s stealthy behavior could give it more opportunity to cause cell transformation and drive tumor development,” Forrest said in the release.

The research involves creating genetically modified viruses that incorporate KSHV genes to simulate human infection and test potential treatments. The study will also explore how immune suppression from the LANA protein influences disease development.

“We’re excited about what we might discover,” Forrest said in the release. “It would be amazing to figure out how this virus can persist in the body for so long and what we can do to prevent it from causing cancer.”