Researchers at Columbia University’s College of Physicians & Surgeons have discovered how the herpes virus that causes chicken pox, known as varicella-zoster virus, or VZV, reactivates in adulthood to cause shingles, an extremely painful and sometimes disfiguring condition. The team’s findings are reported in the June issue of Proceedings of the National Academy of Sciences. The discovery could lead to a better understanding of the process and, eventually, more effective treatments for people who have a significantly higher incidence of shingles because their immune systems have been compromised by cancer or HIV infection.
While it has been known for some time that VZV remains in the body in an inactive, or dormant state, the mechanism by which the virus maintains latency over the course of a lifetime has been a mystery. In most cases, once a child has chicken pox, he or she is immune from contracting the disease a second time. However, in about 15 percent of the population VZV reactivates in adulthood as shingles. Columbia University researchers sought to determine the behavior of the virus throughout the period of latency. “The key questions were what was the virus doing ‘between bouts’ and what causes it to reactivate,” says Saul J. Silverstein, Ph.D., professor and chairman of microbiology at Columbia University.
Other researchers include principal author Octavian Lungu, Ph.D. and Christos Panagiotidis, Ph.D., associate research scientists in microbiology; Paula Annunziato, M.D., assistant professor of pediatrics; and Anne A. Gershon, M.D., professor of pediatrics and an internationally recognized expert on VZV who was instrumental in introducing an anti-VZV vaccine into this country.
To solve these problems, the research team developed unique antibody reagents that reacted with proteins from the virus. The reagents indicate that “latently infected neurons” — those in which the inactive VZV was detected—express proteins that restrict, or regulate, transport of the virus-encoded regulatory proteins. “We found that in the latently infected neurons, virus-encoded proteins get ‘stuck’ in the cytoplasm of these cells. They are restricted from moving into the nucleus, where they are normally found and used to replicate viruses,” Dr. Silverstein says. “It seems that the host has developed a novel mechanism to maintain VZV latency. Ultimately, we hope to understand that mechanism.”
The next step for the researchers is to investigate which cell proteins regulate flow of VZV information. Their hope is to use that knowledge to develop a practical means of preventing reactivation of VZV and eventually to be able to control or prevent altogether the occurrence of debilitating shingles.
The study was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.