Newly published research identifies proteins in EBV-infected cells that decreased expression of genes linked to the spread of the virus, a fresh direction for EBV research.
Epstein-Barr virus is a common, long-lasting virus that affects most individuals. While those infected are often asymptomatic, the virus has been linked to various immunocompromising diseases and cancers—popular news recently reported on a strong connection to Multiple sclerosis (MS). Published in PLOS Pathogens, a new collaborative study led by Italo Tempera, Ph.D., revealed how lamins – proteins in the nucleus of a cell – could affect EBV replication in host cells by influencing the virus genome, ultimately changing how virus genes function.
When a virus such as EBV infects cells, it invades the nucleus of host cells to replicate and spread. Previous research by Tempera – Associate Professor of The Wistar Institute Gene Expression & Regulation Program and Associate Director for Cancer Research Career Enhancement at Wistar’s Ellen and Ronald Caplan Cancer Center – showed that changes to the virus genome helps EBV sustain its infection in hosts.
“Viruses don’t reinvent but use existing machinery,” says Tempera. “EBV has evolved to take every mechanism the host uses to regulate its presence in the nucleus, and it has such profound consequences for the genome that are really fascinating.”
To investigate how genes are regulated to lead to this persistent infection, Tempera and colleagues infected and imaged genetically altered B cells, a type of immune cell. They also employed sequencing to study the virus genome. The team found that lamins – specifically lamins A/C – repressed gene expression linked to replication of the virus’s genetic material.
The team also observed that the infection of B cells with EBV produced the same effect as the activation of B cells by T cells in an immune response. This copying of B cell biology by the virus may help explain why EBV is latent (not recognized by the immune system right away) and further clarify how host cells respond to the invasion of EBV into the nucleus.
“It’s a very basic mechanism,” he says, “but one that can give us a lot of good ideas about how the virus can hijack the host. It’s a really new angle.”
Tempera hopes this work will open new directions in which to study viruses and inspire other researchers to explore how viruses interact with hosts. Regarding therapeutic potential, he muses that with more research, scientists might be able to identify targets for EBV infection that could prevent or turn off genetic expression in cancer. “That could be the long haul of how you move this basic science into something more practical.”