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Herpes Virus Exploits Protein on Skin Cell Surfaces To Enhance Disease

NIAID-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

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

HSV-1 infects an estimated 50 to 80 percent of U.S. adults, according to the Centers for Disease Control and Prevention. The virus typically enters the body through the skin and may cause cold sores or fever blisters in healthy people. In people with compromised immune systems, HSV-1 infection can spread to organs such as the brain, lungs, and liver and develop into life-threatening disease. Those with the skin disease atopic dermatitis, the most common type of eczema, are particularly susceptible to serious complications arising from HSV-1 infection.

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 Study

Working 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.


The team’s findings show that the scavenger receptor MARCO is a major contributor to early steps of HSV-1 skin infection. They also suggest that preventing the interaction of MARCO and viral surface proteins can block HSV-1 infection in the skin. These results could potentially lead to development of new therapies that decrease the risk of life-threatening HSV-1-related complications in atopic dermatitis patients.

Next Steps

The researchers plan to study MARCO in people with atopic dermatitis to identify strategies that may prevent its binding to HSV-1. They also will investigate other skin viruses that may use the same pathway to infection.


MacLeod DT, Nakatsuji T, Yamasaki K, Kobzik L, Gallo RL. HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection. Nature Communications DOI: 10.1038/ncomms2963 (2013)

Last Updated June 05, 2013

Last Reviewed June 05, 2013