Gladstone Scientist Links Latency of the Epstein-Barr Virus to Effectiveness of Chemotherapy Drugs in Cancer

The term latency tends to be linked to HIV, but many other viruses also enter a latent or “resting” phase. The Epstein-Barr virus (EBV), for example, evades the immune system by turning off all of its own genes. EBV, also known as human herpesvirus 4, is one of the most common human viruses, and it creates a global health problem. EBV causes infectious mononucleosis and is associated with nearly one percent of all cancer cases every year, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and other malignancies.

“Epstein-Barr virus is a great virus for studying latency. In fact, it has been studied longer than HIV,” said JJ Miranda, PhD, assistant investigator at the Gladstone Institutes. “By better understanding how and why EBV becomes latent or active, we can develop more personalized medicines to treat malignancies involving the virus.”

During most viral infections, the virus enters a lytic or “active” phase, in which the virus itself makes millions of new virus particles that then go on to infect other cells. However, for reasons that are not yet understood, a small amount of virus goes latent. In other words, the viral DNA inserts itself into the cell’s DNA, where it remains quiet until it is reactivated.

In a study published in the journal Biochemical and Biophysical Research Communications, a team led by Miranda examined how certain drugs affect genes in EBV-infected tumor cells. They determined what genes are active during different periods when the cells are latent. For example, in type I latency, only the viral EBNA1 gene and a few others are expressed, while in type III latency, many other genes are expressed.

Miranda’s team found that cells in type I latency spontaneously reactivated more often than cells in type III latency. They also discovered that the latency type and levels of spontaneous reactivation indicated how effectively chemotherapy drugs reactivated the virus.

“If we can reactivate latent EBV in tumors, then we can also specifically target those tumors with our own immune systems or antiviral drugs,” said Miranda. “By knowing which latent viruses respond to chemotherapy drugs, we can create combination therapies that target the virus and the host cell in specific cancer cases.”