Two cancer-causing viruses are tough to treat because they stay dormant in 95 percent of infected patients. Now scientists have found genes that are key to making them active.
Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) hide within the worldwide human population. While dormant in the vast majority of those infected, these active herpesviruses can develop into several forms of cancer.
In an effort to understand and eventually develop treatments for these viruses, researchers at the University of North Carolina have identified a family of human genes known as Tousled-like kinases (TLKs) that play a key role in the suppression and activation of these viruses.
Blossom Damania, a member of the University of North Carolina Lineberger Comprehensive Cancer Center, and colleagues found that suppressing the TLK enzyme causes the activation of the lytic cycle of both EBV and KSHV. During this active phase, these viruses begin to spread and replicate, and become vulnerable to anti-viral treatments. “When TLK is present, these viruses stay latent, but when it is absent, these viruses can replicate” says Damania, also of the department of microbiology and immunology.
KSHV and EBV are blood-borne viruses that remain dormant in more than 95 percent of those infected, making treatment of these viruses difficult. Both viruses are associated with a number of different lymphomas, sarcomas, and carcinomas, and many patients with suppressed immune systems are at risk for these virus-associated cancers. “The dormant state of these viruses is what makes it so hard to treat these infections and the cancers associated with these infections,” says Damania.
Researchers have known that stimuli such as stress can activate the virus from dormancy, but they do not understand the molecular basis of the viral activation cycle.
With the discovery of the link between these viruses and TLKs, Damania says that researchers can begin to look for the molecular actions triggered by events like stress, and how they lead to the suppression of the TLK enzymes.