By DoM Communications | Date Published: June 18, 2024
Orzalli Lab Demonstrates Herpes Simplex Virus 1 Inhibits Antiviral Pathway in Skin Cells
The skin is an important barrier against pathogens, and skin cells known as keratinocytes generate protective immune responses against infections. One of the defenses that keratinocytes employ is the formation of the NLRP1 inflammasome, a mediator of the inflammatory cell death process known as pyroptosis.
In a new study published in the Journal of Experimental Medicine, Megan Orzalli, PhD, assistant professor of medicine in the Division of Infectious Diseases and Immunology and faculty in the Program in Innate Immunity, along with members of her lab including graduate student Pooja Parameswaran, investigated the interactions between herpes simplex virus 1 (HSV-1), a common human pathogen that initially replicates in keratinocytes and the NLRP1 inflammasome pathway.
Dr. Orzalli’s group observed that while HSV-1 induced phenotypes consistent with activation of the NLRP1 pathway, infected cells do not undergo pyroptosis. They identified the HSV-1 protein infected cell protein 0 (ICP0) as the inhibitor of NLRP1 inflammasome formation and pinpointed the step in the signaling pathway inhibited by this protein. Her group also found that ICP0 was necessary for the activation of the NLRP1 pathway during HSV-1 infection, demonstrating that a single viral protein can both activate and inhibit NLRP1. They showed that NLRP1 activation negatively affected the spread of an ICP0-deficient virus, emphasizing that the virus needs to evolve to evade the NLRP1 inflammasome to productively infect humans.