Oligomerization of Mumps Virus Phosphoprotein

Abstract

The mumps virus (MuV) genome encodes a phosphoprotein (P) that is important for viral RNA synthesis. P forms the viral RNA-dependent RNA polymerase with the large protein (L). P also interacts with the viral nucleoprotein (NP) and self-associates to form a homotetramer. The P protein consists of three domains, the N-terminal domain (P N ), the oligomerization domain (P O ), and the C-terminal domain (P C ). While P N is known to relax the NP-bound RNA genome, the roles of P O and P C are not clear. In this study, we investigated the roles of P O and P C in viral RNA synthesis using mutational analysis and a minigenome system. We found that P N and P C functions can be trans -complemented. However, this complementation requires P O , indicating that P O is essential for P function. Using this trans -complementation system, we found that P forms parallel dimers (P N to P N and P C to P C ). Furthermore, we found that residues R231, K238, K253, and K260 in P O are critical for P's functions. We identified P C to be the domain that interacts with L. These results provide structure-function insights into the role of MuV P. IMPORTANCE MuV, a paramyxovirus, is an important human pathogen. The P protein of MuV is critical for viral RNA synthesis. In this work, we established a novel minigenome system that allows the domains of P to be complemented in trans . Using this system, we confirmed that MuV P forms parallel dimers. An understanding of viral RNA synthesis will allow the design of better vaccines and the development of antivirals.