You may not have heard of cytomegalovirus (CMV), but there’s a good chance you have it. Half of all Americans are infected with CMV without knowing it, as the virus can assume a silent, asymptomatic state which scientists call ‘latency’. The fever, pneumonia, or ulcers marking active disease emerge only when individuals become immunocompromised, as happens in transplant recipients treated with immunosuppressants. And not to long ago—before modern pharmaceuticals made HIV a more manageable condition—CMV was a dreaded “opportunistic” infection, causing blindness in 50% of late stage AIDS patients.
Still, CMV is the number one infectious cause of congenital birth defects worldwide: in this country, 1 in 700-800 babies are infected in utero and hence born with the infection. Those infants can be treated with anti-viral drugs to restrict severe disease or death, but remain at risk for hearing loss and permanent learning disabilities.
On the TRAIL of CMV
The best hope for children or adults infected with CMV is that the virus will go dormant, because even the most healthy immune system never ousts the virus altogether. Recently, LJI scientist and CMV expert Chris Benedict, Ph.D., discovered a major strategy used by the virus to elude the host’s immune system. He discovered that CMV uses one of its genes to block signaling of a protein named TRAIL, a molecule that has been thought to largely control immune responses to cancer, but which Benedict has recently shown to be important in fighting off virus infections as well. This CMV protein, called ‘UL141’, potently blocks attempts by the immune system to clear CMV from our cells, and contributes to the ability of CMV to stay in our bodies for life.
Elucidating how specific strategies used by CMV confer survival advantages to infected cells will instruct us how to develop an effective CMV vaccine, which is not yet available. Benedict has since identified many parts of CMV proteins, called epitopes, that are recognized by T cells in mice. He has shown that vaccination with these viral epitopes protects mice from CMV infection, and has shown that some of these epitopes are much better than others, raising the likely possibility that similar approaches will be feasible in humans.