
The Connector Domain of Vesicular Stomatitis Virus Large Protein Interacts with the Viral Phosphoprotein
Author(s) -
Joseph R. Gould,
Shaowei Qiu,
Qiao Shang,
Tomoaki Ogino,
Peter E. Prevelige,
Chad M. Petit,
Todd Green
Publication year - 2020
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01729-19
Subject(s) - phosphoprotein , biology , mononegavirales , vesicular stomatitis virus , virology , rhabdoviridae , virus , rna , microbiology and biotechnology , paramyxoviridae , genetics , phosphorylation , gene , viral disease
Vesicular stomatitis virus (VSV) is an archetypical member of Mononegavirales , viruses with a genome of negative-sense single-stranded RNA (-ssRNA). Like other viruses of this order, VSV encodes a unique polymerase, a complex of viral L (large, the enzymatic component) protein and P (phosphoprotein, a cofactor component). The L protein has a modular layout consisting of a ring-shaped core trailed by three accessory domains and requires an N-terminal segment of P (P N-terminal disordered [P NTD ]) to perform polymerase activity. To date, a binding site for P on L had not been described. In this report, we show that the connector domain of the L protein, which previously had no assigned function, binds a component of P NTD We further show that this interaction is a positive regulator of viral RNA synthesis, and that the interfaces mediating it are conserved in other members of Mononegavirales Finally, we show that the connector-P interaction fits well into the existing structural information of VSV L. IMPORTANCE This study represents the first functional assignment of the connector domain of a Mononegavirales L protein. Furthermore, this study localizes P polymerase cofactor activity to specific amino acids. The functional necessity of this interaction, combined with the uniqueness of L and P proteins to the order Mononegavirales , makes disruption of the P-connector site a potential target for developing antivirals against other negative-strand RNA viruses. Furthermore, the connector domain as an acceptor site for the P protein represents a new understanding of Mononegavirales L protein biology.