Two mutations in the HR2 region of Newcastle disease virus fusion protein with a cleavage motif “RRQRRL” are critical for fusogenic activity

Background Newcastle disease virus (NDV) causes severe diseases in avian species. Its fusion protein cleavage site (Fcs) is a major contributor to virulence and membrane fusion. Previous studies showed that a change from phenylalanine (F) to lysine (L) at position 117 of the virulent strain fusion protein, which has the polybasic amino acid Fcs motif “112RRQKR↓F117”, blocked syncytium formation. However, we observed that F proteins of the virulent strain F48E9 and avirulent strain LaSota substituted with an identical cleavage motif, “112RRQRR↓L117”, induced extensive and slight syncytium formation, respectively. Accordingly, we hypothesized that the difference in syncytium formation is caused by other regions of the fusion protein.