Tricking the herpes virus out of “hiding”
Herpes is a huge health problem. Twenty million to 30 million Americans have recurrent genital herpes outbreaks, and 700,000 new genital herpes simplex virus infections occur every year. More than 2,000 babies are born with a herpes infection annually, even though 40,000 caesarians are performed due to a fear of transmitting herpes from mother to child.
The herpes simplex virus is a complex high-performance engine designed to replicate itself. When it enters a human host, it encounters an army of cellular defense proteins designed to turn off these engines and prevent the virus from multiplying.
But the herpes virus is capable of fighting back. It can shut down attempts by its host to block it. In skin abrasions and cells lining the mouth or genitals of the host, the virus prevails by overcoming the host’s cellular defenses.
Then, after the herpes virus gets past its host’s cellular defenses and begins to multiply, it infects the host’s neurons. Here a different story takes place.
In neurons, the herpes virus allows itself to be silenced by its host’s defenses and lies dormant until it is activated by hormones or stress on the neurons.
While the virus is dormant it is not vulnerable to antiviral drugs, but when the virus is fighting its host’s cellular defenses it is vulnerable. That’s why Bernard Roizman, ScD, Joseph Regenstein Distinguished Service Professor of Virology and Chair of the Viral Oncology Laboratory at the University of Chicago, and his colleagues are focusing their herpes research on the mechanism by which the host silences the virus. Their work is supported by a two-year $581,604 grant from the National Institutes of Health that has allowed them to hire two fulltime employees, one at the postdoctoral level and one technical assistant.
Waking a sleeping giant
The primary health threat posed by the herpes virus occurs when it is reactivated from its dormant state and causes both new lesions in the person who harbors the virus and in others with whom the host comes into contact.
Today, individuals harboring dormant viruses cannot be cured. One approach that might cure herpes, however, is to disrupt the silencing mechanism harbored in the host’s neurons. This would allow the virus to multiply, at which point the virus could be killed by newly designed antiviral drugs.
To achieve this, Roizman and his colleagues need to know the mechanism by which the virus is silenced in neurons. “We know a lot about host’s cellular defenses at the sites of entry into the body,” he says. “Now, our foremost question is whether the same defenses are operating in neurons.”
If the answer is “yes,” the researchers will be able to begin to develop drugs that temporarily disrupt those defenses. “For now, my University of Chicago research associates Haidong Gu, MD, Grace Zhou and Te Du and I are designing mutant test viruses that will act as ‘Trojan’ viruses aimed at elucidating the neurons’ defense mechanism,” Roizman says.
by Greg Borzo
This award is funded under the American Recovery and Reinvestment Act of 2009, NIH Award number: 3R37CA078766-12S1. For more information on NIH’s Recovery Act projects, visit http://recovery.nih.gov/.
Bernard Roizman, Professor and Chair of the Viral Oncology Laboratory at the University of Chicago, and associates received a two-year $581,604 grant from the NIH to conduct breakthrough research that could make antiviral drugs more effective against the herpes virus. (Photo by Lloyd DeGrane.)
