Contents:

Pediatric Cancer
Varicella Zoster
Technology Transfer
The Short White Coat
Research Briefs
Around & About
POV


The rash of chickenpox can drive a person temporarily crazy because of the terrible itching. But the disease course usually is relatively tolerable, generally lasting about a week, compared with chickenpox’s cousin, shingles, which in severe cases can cause stabbing pain lasting for months, or even years.

The culprit behind chickenpox and shingles is a herpesvirus called varicella zoster virus. After initial infection, chickenpox, also known as varicella, can invade the nervous system and stay dormant for many years, only to reactivate and return to the skin as shingles, or zoster. Fortunately, the varicella vaccine usually protects against chicken- pox and zoster. Columbia Health Sciences researchers played a significant role in approval of the vaccine by the FDA in 1995. Since then, the investigators have been studying how the virus spreads, which may lead to better ways to fight the virus.

The Columbia varicella zoster virus research group, led by Dr. Anne Gershon, professor of pediatrics at P&S, has examined the development of infectious particles in vitro and defined the role of envelope glycoproteins in the viral life cycle. She highlighted her work in the Feb. 28 Dean’s Distinguished Lecture.

The envelope, according to Dr. Gershon’s research, apparently is unnecessary for most cell-to-cell transmission of the virus within the body but is required for spread into the nervous system and from person to person. Enveloped virus has been found only in the skin vesicles of varicella and zoster cases.

The enveloped virus creates the chickenpox rash and can travel from the skin to sensory nerves. Once in the sensory nerves, the virus moves to the sensory ganglia where it becomes latent. If reactivated, the virus travels from the sensory ganglia back to the skin where it creates the shingles rash.

The virus is transmitted by airborne viral particles shed from the skin of an infected person. The new host breathes in the virus, which enters the mucous membrane in a person’s respiratory tract and begins to spread without its envelope from cell to cell. The virus invades T-cells of the blood and those T-cells carry the virus to the skin. There, the virus can recreate its envelope because the top layer of the skin lacks the endosomal pathway that removes glycoproteins from the envelope.

As the enveloped virus builds up, it creates the characteristic chickenpox rash. From there, the virus can aerosolize again and infect a new host. But enveloped viruses, which have mannose 6-phosphate in their glycoprotein envelope, can travel from the skin to sensory nerves. The varicella zoster virus is drawn to sensory nerve cells by their mannose 6-phosphate receptors.

The enveloped virus infects the sensory nerves without causing any damage and travels to the sensory ganglia where it becomes latent. This latent infection activates into zoster usually in the elderly and people whose immune systems are weakened. (Healthy immune systems typically prevent the infection from developing.)

Dr. Gershon arrived at many of the steps in the varicella infectious pathway by studying a mutant form of the virus that was unable to form an envelope.

Recently, using an enveloped virus, the researchers have been able to establish a latent infection in guinea pig small intestine neurons, or what they call “shingles in a dish.” The work will soon be reported in the Journal of Medical Virology. This guinea pig model appears to be the first in vitro cell model for latency of varicella zoster virus. Dr. Gershon and her colleagues are trying to get the latent virus to reactivate.

“If we can get the virus to reactivate, that would be really exciting,” Dr. Gershon says. “Nobody’s developed a true cell culture model of the virus, which would give us the ability to look at many phenomena such as the effect of antiviral drugs and viral mutants.”

She hopes further guinea pig studies will lead to new treatments for people with zoster and new vaccines for varicella. Dr. Gershon and her colleagues showed that the varicella vaccine was safe and effective by testing small and then large populations of children and adults. The vaccine is the first live, attenuated herpesvirus vaccine to be licensed in the United States.

The varicella vaccine has the envelope but the weakened version of the virus normally is not strong enough to form skin lesions and the body’s immune system fights the mild infection. Enveloped particles rarely are present after vaccination, effectively preventing the occurrence of zoster—although zoster infections have occurred in rare cases after vaccination.

The current varicella vaccine, while effective, provides protection in about 80 percent of vaccinated people. “I would like to have a vaccine that works on everyone who gets it,” Dr. Gershon says. “Further studies of how the current vaccine works may result in even better vaccines in the future.”


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