Herpes Virus Exploits Protein on Skin Cell Surfaces to Enhance DiseaseNIAID-supported investigators have shown that herpes simplex virus type 1 (HSV-1) binds to a protein called MARCO on the surface of skin cells to boost its infectivity and disease-causing potential. Blocking this interaction limited viral infection in mice, suggesting a potential new approach to prevent and treat herpes infection. The researchers report their results in the June 6, 2013, issue of Nature Communications.
Red indicates areas where HSV-1 and MARCO interact on the surfaces of cultured human skin cells. Cell nuclei are shown in blue. Credit: Gallo Laboratory, University of California, San Diego
During the first step of infection, proteins on the outer shell of HSV-1 bind to receptors on the surface of a skin cell. Simultaneously, the immune system recognizes the virus as harmful and springs into action to fend off the intruder. This protective response includes a group of proteins called scavenger receptors, which are thought to help the immune system recognize pathogens.
While investigating the interactions between scavenger receptors and HSV-1, scientists in the NIAID-supported Atopic Dermatitis Research Network (ADRN) found that the virus unexpectedly exploits its contact with the scavenger receptor MARCO to gain entry into cells.
Results of StudyWorking with laboratory-grown human skin cells, the ADRN team led by Daniel MacLeod, Ph.D., and Richard Gallo, M.D., Ph.D., of the University of California, San Diego, found that MARCO interacts with HSV-1 by binding to a viral surface protein. Cells engineered to produce large amounts of MARCO were more susceptible to HSV-1 infection than normal skin cells.
By comparing HSV-1 infection in normal mice and in mice lacking MARCO, the scientists found that MARCO enhances the virus’ ability to infect the skin. Eight days after HSV-1 infection, lesions on the skin of mice lacking MARCO were 71 percent smaller than those on the skin of normal mice. In a separate experiment, the investigators observed that molecules that bind to MARCO inhibited viral attachment to skin cells of normal mice and reduced the size of the lesions.