Epstein-Barr virus (EBV) is a common pathogen - virtually everyone is infected at one point in their lives - that can cause mononucleosis (or "mono") and two rare forms of cancer.
Scientists at the medical school have discovered a protein that is essential for the assembly of the virus, an important advance that might help researchers design new antiviral drugs to treat EBV and other related herpesviruses.
A team at the Sidney Kimmel Comprehensive Cancer Center, led by virologist Prashant Desai, has been studying capsids, the protein shell of viruses. "Most of our studies have been on herpes simplex virus capsids," Desai said.
EBV is a member of the large class of herpesviruses that cause a range of infectious diseases, including various STIs and several types of cancer.
Knowledge about the structure and assembly of a capsid from its protein subunits is important for understanding the mechanisms of viral transmission and illness. Unfortunately, little is known about the capsids of the class of herpesviruses that includes EBV.
"The herpesvirus capsids are made up of six proteins that interact together to produce an icosahedral structure. The capsid proteins have an inherent ability to self-assemble into these structures if expressed together." An icosahedron is a solid object with 20 sides.
EBV and related viruses are notoriously difficult to work with in cell culture. Instead, Desai and his team found a way to express and purify the capsid proteins in insect cells. "Because this method works so well we can really probe the assembly of these structures using mutational studies," Desai said.
They found that those six capsid proteins are the only ones required for assembly of the shell of EBV, like in other viruses of that type. In other words, given the six proteins, the viral capsid can self-assemble inside the cell.
By mutating the six proteins one by one, Prashant's team was able to investigate the role of each of the proteins in the assembly of EBV. They found one protein in particular to be important. "We have discovered that a small protein that decorates these capsids is essential for assembly. Thus this small capsid protein could potentially serve as a new antiviral target for gammaherpesviruses (the class of virus that includes EBV)," Desai said.
Desai believes that drugs could be made to disrupt the functioning of the protein, preventing assembly of the capsids and thereby making it harder for the viruses to reproduce.
In addition to being a possible target for future antivirals, these capsids have other medical uses. First, they could be used to trace infection in living cells by tracing the presence of the capsid proteins. Desai pointed to Kaposi's sarcoma herpesvirus (KSHV), another cancer-causing virus that is closely related to EBV.
"The small capsid protein in KSHV is an important immunological reporter for KSHV infection and so these capsids can also serve as a new platform for developing serological tools," Desai said.
Serological tools are methods of determining the presence of specific proteins in the bloodstream. The presence of KSHV capsid in the blood is a sensitive sign of infection by the virus - one that might be easier to detect than the full virus or its DNA.
Furthermore, these capsids are plausible candidates for vaccines, since they do not contain any viral genetic material and therefore cannot produce an infection.
The vaccine against human papillomavirus, which prevents infection by the virus that causes cervical cancer, was made from virus-like particles, which stimulate the immune system but are not infectious.
The empty capsids of EBV and related herpesviruses could therefore be used to stimulate an immune response without causing illness, thus conferring immunity against viral infections. Capsids are thought to be safer than living or damaged viruses.
