NIH Research Matters
October 27, 2006
Human Protein Helps Chickenpox and Shingles Virus Spread
Researchers have identified a human protein that the varicella-zoster virus, which causes both chickenpox and shingles, uses to spread from cell to cell within the body. Interfering with this interaction inhibits the spread of virus among cells in the test tube. The discovery suggests a new way for designing therapies for shingles.
Once chickenpox has run its course, some virus remains dormant in nerve cells at the base of the brain and alongside the spinal cord. In older people or those with a weakened immune system, the virus can reactivate years later and travel through the nerve cells to the skin. There it multiplies, damaging sensory nerve endings and causing the blistering rash of shingles. The rash usually heals within a few weeks, but the nerve damage can cause one of the worst complications of shingles: a severe type of pain called postherpetic neuralgia that can last for months or even years.
Shingles drugs already exist to prevent viral replication, speed healing and reduce the severity of the disease. But sometimes they’re less effective in people with weakened immune systems. Just this year, the Food and Drug Administration licensed a shingles vaccine for people 60 and older after a large clinical trial showed that the vaccine could reduce the expected number of shingles cases by half in this age group. Yet some of the most vulnerable to shingles — those with AIDS and others with weakened immune systems — can’t receive the vaccine because it’s made from a live virus.
Virologists Dr. Jeffrey I. Cohen, Dr. Qingxue Li and Dr. Mir Ali at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) have been working to gain a better understanding of the varicella-zoster virus in order to design more effective therapies. A few years ago, they discovered that if they deleted a molecule called glycoprotein E on the surface of the virus, it 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. The team used glycoprotein E as a sort of hook to fish out a human protein to which it binds.
In the October 20, 2006 issue of the journal Cell, the researchers report that the human protein to which varicella-zoster virus attaches is called insulin-degrading enzyme. Interfering with the cells’ production of the protein significantly reduced the infectivity of the virus and blocked its cell-to-cell spread. Conversely, genetically altering mouse and hamster cells, which are normally resistant to the virus, to produce human insulin-degrading enzyme rendered the cells more susceptible to varicella-zoster virus infection.
The researchers 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 is too high for people to take safely, the finding suggests that the new receptor might be a valid target for possible future shingles and chickenpox treatments.
NIH Research Matters
Bldg. 31, Rm. 5B64A, MSC 2094
Bethesda, MD 20892-2094
About NIH Research Matters
Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.
NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.