Newcastle disease virus hemagglutinin-neuraminidase and fusion protein (NDV HN/F)

Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) and fusion (F) proteins are essential surface glycoproteins that coordinate viral entry into host cells. HN facilitates initial attachment by binding to sialic acid-containing receptors and provides neuraminidase activity to prevent viral clumping, while the F protein undergoes a conformational change to merge the viral envelope with the host cell membrane (UniProt P04872, P06190). In oncology, these proteins are utilized within a recombinant vesicular stomatitis virus (rVSV) backbone, where they replace the native VSV-G protein to create a chimeric oncolytic virus with enhanced tumor specificity and reduced systemic toxicity (Zamarin et al., 2014, Gene Therapy). This therapeutic approach leverages the fact that many cancer cells have defective interferon signaling, making them highly susceptible to viral replication and the subsequent induction of syncytia—large multinucleated cells formed by the fusion of infected cells with neighboring cells. This process not only causes direct tumor lysis but also releases tumor-associated antigens and danger signals, stimulating a robust systemic anti-tumor immune response (Vigil et al., 2007, Cancer Research).

Other names

NDV HNNDV FAvian orthoavulavirus 1 glycoproteinsrVSV-NDV-HN/FNewcastle disease virus attachment and fusion proteinsHemagglutinin-neuraminidaseFusion glycoprotein

The HN protein binds to sialic acid receptors on the cancer cell surface, while the F protein mediates pH-independent membrane fusion, allowing the rVSV vector to enter the cell, replicate, and induce syncytia formation and immunogenic cell death.