|NIAID Scientists Identify Human Protein that
Helps Chickenpox and Shingles Virus Spread
A team of scientists at the National Institute of Allergy and
Infectious Diseases (NIAID), one of the National Institutes of
Health (NIH), has identified a human protein that helps varicella-zoster
virus, the cause of both chickenpox and shingles, spread from cell
to cell within the body.
NIAID virologist Jeffrey I. Cohen, M.D., and NIAID research fellow
Qingxue Li, M.D., Ph.D., discovered that a surface protein of varicella-zoster
virus attaches to a cellular protein called insulin-degrading enzyme,
using it as a receptor to enter and infect cells. In the October
20, 2006 issue of the journal Cell, they also describe
how interfering with this interaction inhibits the spread of virus
among cells in the test tube. The discovery of this receptor is
important in understanding varicella-zoster virus, say Drs. Cohen
Their finding is also an important first step towards designing
new therapies for shingles. “If safe and effective ways of disrupting
this interaction can be found, eventually new interventions may
be developed for treating people with this painful and debilitating
disease,” says NIAID Director Anthony S. Fauci, M.D.
Shingles occurs only in people who have already had chickenpox.
Once chickenpox has run its course, some virus remains dormant
in nerve cells at the base of the brain and alongside the spinal
cord. With advancing age or and diminished immunity, the virus
can reactivate years later and travel down the nerve cells to the
skin. There it multiplies, causing the blistering rash of shingles
and damaging sensory nerve endings. The rash usually heals within
a few weeks, but the nerve damage sometimes causes one of the worst
complications of shingles — a severe type of pain called
postherpetic neuralgia, which can last for months or even years.
Shingles drugs already exist that prevent viral replication, speed
healing and reduce the severity of the disease. But some people
who are immunocompromised develop a disseminated infection and
resistance to these drugs. “An additional drug against a completely
different type of target might be useful for these people,” says
Just this year, the Food and Drug Administration licensed a shingles
vaccine for people 60 and older after a large clinical trial carried
out in collaboration with NIAID showed that the vaccine could reduce
the expected number of shingles cases by half in this age group.
Yet ironically, says Dr. Li, some people who are the most vulnerable
to shingles — people with AIDS and others who are severely
immunocompromised — cannot receive the vaccine because it
is made from a live virus.
The NIAID research began a few years ago when Dr. Cohen and his
colleagues discovered that if they deleted a molecule called glycoprotein
E on the surface of the virus, the virus lost its ability to infect
human cells. This led them to reason that glycoprotein E is involved
in the virus’ infectivity, and it gave them a way to search for
its receptor. Working with biologist Mir Ali, Ph.D., the team used
glycoprotein E as a sort of hook to fish out a human protein to
which it binds.
Dr. Li found that curtailing the expression of insulin-degrading
enzyme within cells significantly reduced the infectivity of the
virus and blocked its cell-to-cell spread. Conversely, genetically
altering mouse and hamster cells to express human insulin-degrading
enzyme rendered these cells more susceptible to varicella-zoster
virus infection. Normally cells from hamsters and mice are resistant
to the virus, which in nature only infects humans.
Drs. Li and Cohen also found that they could block the virus’ cell-to-cell
spread by adding compounds that prevented glycoprotein E from binding
to insulin-degrading enzyme. One such compound was the common topical
antibacterial ingredient bacitracin. Although the amount of bacitracin
needed to effectively block the interaction in the laboratory would
be too high for people to take safely, the finding suggests the
new receptor might be a valid target for new shingles and chickenpox
NIAID is a component of the National Institutes of Health.
NIAID supports basic and applied research to prevent, diagnose
and treat infectious diseases such as HIV/AIDS and other sexually
transmitted infections, influenza, tuberculosis, malaria and
illness from potential agents of bioterrorism. NIAID also supports
research on basic immunology, transplantation and immune-related
disorders, including autoimmune diseases, asthma and allergies.
News releases, fact sheets and other NIAID-related materials
are available on the NIAID Web site at http://www.niaid.nih.gov.
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Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
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