Herpes viruses are good at hiding. They infect human cells and lay dormant there until replication is activated by stress or some other environmental factor. One type, Kaposi’s sarcoma-associated herpesvirus (KSHV), is one of only a few viruses known to cause cancer.
In a study that appeared online September 17 in the journal EMBO Reports, Sanford-Burnham’s Dr. Tariq Rana and colleagues found that KSHV stays quiet by expressing certain microRNAs (miRNAs), small strands of genetic material that interfere with protein production.
“KSHV dormancy is believed to be essential for tumor formation, yet some forms of cancers caused by the virus have also been linked to viral reactivation,” explains Dr. Rana, professor and director of Sanford-Burnham’s RNA Biology Program. “This study helps us better understand the KSHV life cycle, thus providing new insight into how the virus causes cancer in some populations.”
Until recently, RNA had been thought of simply as a messenger, transferring information encoded in the genome to cellular machinery that produces proteins (see DNA 101). But in the past 10 years, scientists have found that miRNA play an active role in controlling which genes are turned on or off—processes that could have a profound impact on human health.
KSHV is known to produce up to 17 different miRNAs during the silent phase of infection. Dr. Rana’s group identified one miRNA used by the virus to influence gene expression in a way that stabilizes dormancy. How? The fragment, called miR-K3, shuts down factors in the infected cell’s nucleus that are necessary for viral replication. The research team also showed they could block viral replication by adding more miR-K3 to the system or by removing the nuclear factor it acts upon.
“To further understand the genetic networks used by KSHV miRNAs to control viral latency or replication, we are now looking at global phenomena in host cells after KSHV infection, such as changes in RNA or protein production,” Dr. Rana says. “We hope that these studies will provide us with a broad picture of how KSHV communicates with host systems and hopefully provide new targets to develop anti-KSHV therapies.”