Membrane cofactor protein (CD46) and Nectin-4 (Poliovirus receptor-related protein 4) (CD46/Nectin-4)

Measles virus receptors, primarily Membrane cofactor protein (CD46) and Nectin-4 (Poliovirus receptor-related protein 4), are the critical cellular entry points exploited by oncolytic measles viruses such as TMV-018 [1, 2]. CD46 is a ubiquitously expressed transmembrane protein that protects host cells from complement-mediated damage, while Nectin-4 is a cell adhesion molecule typically found in epithelial adherens junctions and frequently overexpressed in various adenocarcinomas [1, 2]. In oncolytic virotherapy, the Edmonston vaccine strain of the measles virus is engineered or naturally predisposed to utilize these receptors to selectively infect, replicate within, and lyse malignant cells [3]. The interaction between the viral hemagglutinin protein and these host receptors triggers membrane fusion, leading to the formation of multinucleated syncytia and eventual cell death [4]. This process not only destroys the tumor directly but also releases tumor-associated antigens, thereby stimulating a robust systemic anti-tumor immune response [4]. Consequently, the expression levels of CD46 and Nectin-4 on tumor cells serve as critical determinants of the therapeutic efficacy of agents like TMV-018 [3].

Other names

CD46Membrane cofactor proteinMCPNectin-4PVRL4Poliovirus receptor-related protein 4SLAMF1Signaling lymphocytic activation moleculeCD150MV-R

Viral attachment to host receptors followed by membrane fusion and intracellular replication, leading to oncolysis and immunogenic cell death.