Sniffing out High-Risk EBV Strains

A*STAR scientists have identified two Epstein-Barr virus strains associated with a high risk of causing nasopharyngeal carcinoma.

Cantonese cancer

Since it was discovered over 50 years ago, the Epstein-Barr virus (EBV) has been linked to cancers such as nasopharyngeal carcinoma (NPC), a cancer of the nose that is also known as Cantonese cancer. Although EBV infects an estimated 95 percent of the population, only a small percentage of people with the infection develop NPC. The reason the virus causes cancer in some individuals but not others is poorly understood.

Now, an international team of scientists led by Jianjun Liu from A*STAR’s Genome Institute of Singapore (GIS), has discovered for the first time two strains of EBV that are associated with an increased risk of NPC.

To determine the unique genetic code of different EBV strains, the team first performed large-scale whole-genome sequencing on EBV isolates from patients diagnosed with EBV-associated cancers—namely NPC, gastric carcinoma and lymphomas—and compared them to healthy controls. These samples were collected from NPC-endemic areas of southern China like Guangdong and Guangxi provinces, and other non-endemic regions of China.

After comparing the genetic sequences between the EBV isolates from patients and the ones obtained from healthy people living in similar regions, the team found two EBV coding variants that are associated with high risk for developing NPC. The team also performed a principal component and phylogenetic analysis to investigate the origin of these risk variants.

“Such analyses can help us understand how these strains or risk variants arise in human populations,” explained Liu.

The two viral strains associated with an increased NPC risk harbored genetic variation in the BALF2 gene, which codes for a DNA binding protein integral for viral DNA replication and viral propagation. These two variant strains were absent or extremely rare in non-Asian people from Africa, and western countries such as Australia, the United States and the United Kingdom.

“Our results from the phylogenetic analysis showed that the variants originated in Asia or China, and underwent a clonal expansion,” said Liu, further noting that “the most important aspect of our discovery is that it explains the NPC endemics in Southern China.”

EBV is a human virus that spreads via bodily fluids like semen, blood and saliva, making it easily transmittable. The discovery of these risk variants thus allows for the development of screening kits to identify high-risk individuals for clinical evaluation and early diagnosis.

“Our findings have also revealed a new target for the development of vaccines and therapies against the virus,” Liu added. Such interventions can help reduce the incidence rate of NPC among susceptible populations through early detection and treatment.

Expanding on the present findings, the team is now working with two cancer centers in Singapore to determine if these virulent strains exert similar effects in Southeast Asia.

The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore (GIS).