Accessory viral protein, V, of Newcastle Disease Virus binds dsRNA to facilitate immune evasion.

Newcastle disease virus (NDV) is an avian paramyxovirus known to infect more than 250 bird species across the globe. NDV is enveloped and carries a negative-sense RNA genome that codes for six structural proteins and two accessory proteins expressed through a unique co-transcriptional RNA editing mechanism. One of the accessory viral proteins, V protein, is multifunctional and a well-known interferon (IFN) antagonist. The overexpression of V protein is known to enhance viral production kinetics during NDV infection. In this study, we elucidated the events that lead to this augmented viral replication. The V protein overexpression downregulated the expression of host RNA sensor, namely MDA5. Furthermore, during the over-expression of V protein in NDV infected cells, the V protein aggregated in the perinuclear region, co-localizing and binding with the replicating dsRNA. Our structural studies and in silico predictions suggest that V protein binding with dsRNA interferes and competes with MDA5 for binding to dsRNA, eventually disrupting the IFN induction and facilitating the viral replication. This study reports a novel mechanism of host immune evasion by the accessory V protein. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-024-00908-4.