Vaccinia virus K2L protein (K2L)

Vaccinia virus K2L protein, also known as Serine Protease Inhibitor 3 (SPI-3), is a viral glycoprotein encoded by the K2L gene in orthopoxviruses. It functions as an endogenous viral fusion inhibitor by forming a heterodimeric complex with the viral hemagglutinin (A56) on the surface of infected cells. This A56/K2 complex interacts with and suppresses the activity of the viral entry-fusion complex (EFC), which is responsible for membrane fusion during viral entry and cell-cell spread. By inhibiting the EFC, K2L prevents the fusion of infected cells with adjacent uninfected cells (syncytia formation) and protects the infected cell from superinfection by other virions. In the absence of K2L, infected cells undergo extensive polykaryocytosis, a phenotype known as fusion-from-within. This property is exploited in the development of oncolytic viruses, such as FUVAC, where K2L is mutated or deleted to enhance the virus's ability to spread through tumor tissue and induce immunogenic cell death.

Other names

SPI-3Serpin-3Serine protease inhibitor 3Orthopoxvirus fusion inhibitor glycoprotein SPI-3K2 proteinK2L protein

Genetic deletion or mutation of the K2L gene to promote syncytia formation and enhance viral spread and oncolysis in tumor tissues.