An unusual enzyme never before seen in viruses appears to shield an AIDS-related skin disease virus from the ravages of ultraviolet (UV) radiation and the immune system, according to a study by researchers from the National Institute of Allergy and Infectious Diseases (NIAID). "This is an interesting finding that uncovers yet another strategy that viruses use to protect themselves from harsh environments," says NIAID Director Anthony S. Fauci, M.D. The molluscum contagiosum virus (MCV) causes a persistent and sometimes disfiguring skin disease common among HIV- infected individuals and others with weakened immune systems. In 1996, researchers led by Bernard Moss, M.D., Ph.D., chief of NIAID's Laboratory of Viral Diseases (LVD), reported the entire genetic sequence of MCV. Analysis of the MCV genome revealed a viral gene whose sequence was very similar to that of the gene for an important human enzyme, glutathione peroxidase. This enzyme neutralizes caustic chemicals called peroxides made by immune system cells to fight infection.
In the Jan. 2, 1998 issue of the journal Science, Dr. Moss and colleagues from the LVD and Harvard Institutes of Medicine in Boston, Mass., report that the MCV gene, like its human counterpart, encodes a protein that contains selenium, a relatively rare element found in only a small number of proteins. Previously, none of these so-called selenoproteins had been identified in viruses.
When the researchers engineered human cells to express the MCV selenoprotein, these cells were largely protected from exposure to UV radiation and peroxides. Ordinarily, explains Dr. Moss, UV radiation and peroxides are cytotoxic, causing cells to die through a process known as apoptosis.
These findings notwithstanding, Dr. Moss and his colleagues note that it is too early to determine definitively the actual role the selenoprotein plays within the virus. The lack of a good animal model of MCV infection and the virus's inability to grow in tissue culture hinder efforts to find this information. However, the researchers speculate that since MCV resides exclusively in human skin, the virus "captured" the selenoprotein gene as a means of defending itself against ultraviolet radiation and the immune system.
Based on the fact that the sequence of the MCV gene is nearly 75 percent identical to the sequence of the human glutathione peroxidase gene, they also speculate that the virus acquired the gene relatively recently in its evolutionary history. Other MCV genes that share sequence similarities with known human genes are only 20 to 25 percent identical to their human counterparts.
This would seem to be a clever ploy for a virus that replicates in the epidermis," Dr.Moss and his co-authors conclude. Dr. Moss adds that in addition to advancing our understanding of how MCV interacts with its human host, this finding could provide useful insights into the workings of the human glutathione peroxidase enzyme. In future studies, he and his colleagues will continue to characterize and compare the viral and human proteins.
In addition to Dr. Moss, collaborators on this study included Joanna L. Shisler, Ph.D., and Tatiana G. Senkevich, Ph.D., both of the LVD, and Marla G. Berry, Ph.D., of the Harvard Institutes of Medicine in Boston, Mass. Dr. Berry's research was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
NIAID supports research on AIDS, malaria, tuberculosis and other infectious diseases, as well as allergies and immunology. NIAID and NIDDK are components of the National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services.
Reference: Shisler JL, Senkevich TG, Berry MJ, Moss B. Ultraviolet- induced cell death blocked by a selenoprotein from a human dermotropic poxvirus. Science 1998;279:102-105. Press releases, fact sheets and other NIAID-related materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov.