What's That Virus Doing With My Genes?
"In order to defeat your enemies, you must make them your friend and keep them close to you." -- From the TV series "X files".
Herpesviruses coexist and "befriend" the immune system so that they can spread throughout the population. Most readers have a herpesvirus in them. The more common herpesviruses cause cold sores and mononucleosis (mono or kissing disease). These herpesviruses are similar to but not the same as the virus upon which I work. This virus is called cytomegalovirus (CMV, cyto=cell, megalo=big) because when it infects cells, they become enlarged. In the vast majority of cases CMV infection causes no disease at all. Only when CMV infection occurs during pregnancy does CMV lead to mental retardation, hearing loss, and in a few cases even death of the newborn. Understanding how CMV causes disease and spreads will help to develop safe, effective vaccines and treatments.
Recently, scientists have found that CMV carries a gene that resembles a gene from our immune system. This gene produces a protein that attracts cells of the immune system much like the gene in humans. Why would the virus want to attract and trigger the immune system? My research is focusing on this question. My hypothesis is that human CMV triggers the immune system in order to infect the infiltrating cells. These cells will deliver the virus to different organs of the body and eventually to the bone marrow where the virus will remain dormant for the life of the host.
My hypothesis is based on an example from mouse CMV. Mouse CMV produces
a protein called MCK. This protein is similar to a normal mouse protein
that attracts and activates immune cells. Our lab has shown that the MCK
also recruits and activates immune cells and that a mutant mouse CMV lacking
MCK cannot disseminate to the salivary glands. Infection of the salivary
gland is important for mouse CMV because the virus spreads from one mouse
to the next in saliva during biting and licking. These experiments demonstrate
that mouse CMV uses MCK to activate the immune system, which allows mouse
CMV to spread.
If I'm able to show that a virus lacking vCXC-1 cannot spread, eliminating that gene from human CMV could make a good vaccine candidate. This weakened virus-vaccine would still induce a protective immune response without spreading throughout the population.
|Modified 15 January 2003 * Contact Us|