Different functions of the common P/V/W and V-specific domains of rinderpest virus V protein in blocking interferon signalling

The V proteins of paramyxoviruses are composed of two evolutionarily distinct domains, the amino-terminal 75% being common to the viral P, V and W proteins and not highly conserved between viruses, while the remaining 25% consists of a cysteine-rich V-specific domain which is conserved across almost all paramyxoviruses. There is evidence supporting a number of different functions of the V proteins of morbilliviruses in blocking the signalling pathways of type I and II interferons, but it is not clear which domains of V are responsible for which activities, and whether all these activities are required for effective blockade of interferon signalling. We show here that the two domains of rinderpest virus V protein have distinct functions, the N-terminal domain acting to bind STAT1 while the C-terminal V-specific domain interacts with the interferon-receptor associated kinases Jak1 and Tyk2. Effective blockade of interferon signalling required the intact V protein.