A team of University of Kentucky researchers has identified the roles that herpes simplex virus type 1 (HSV-1) proteins play during the invasion of cells and the formation of skin lesions known as cold sores and fever blisters.
The team, led by microbiology, immunology and molecular genetics associate professor Robert Geraghty, said that after the virus binds to the cell surface, two proteins are triggered to merge with the cell's lipid layer, while a third protein "penetrates" the merged lipid layer to provide virus access to the cell.
The findings advance existing understanding of how HSV-1 attacks cells. Geraghty's earlier work had identified how a protein, Nectin-1, that is important for skin adhesion, is targeted by an HSV-1 protein, called "gD," that affixes itself to Nectin-1.
Immediately after gD has affixed itself to the skin cell's Nectin-1, the two proteins begin blending with the cell surface's lipid layer. Geraghty said those proteins are referred to as "gH" and "gL." After those two act on the cell's surface, a fourth protein, "gB," actually fuses with the skin cell to permit the virus to invade.
Geraghty's team is now screening peptides that could block the action of gH, gL and gB, thereby preventing the occurrence of HSV-1 infections or reducing the severity of HSV-1 episodes in herpes sufferers.
The research also has implications for understanding how similar viruses attack the body. Among the related viruses are cytomegalovirus, Epstein-Barr, Kaposi's sarcoma, varicella-zoster (causes chicken pox and shingles), and several animal herpes viruses, including those that attack horses, pigs and cattle.
Geraghty's project is funded under a five-year grant from the National Institute of Allergy and Infectious Diseases. The project is scheduled to end next February. His findings have been published in Virology , the Journal of General Virology and the Proceedings of the National Academy of Sciences .