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Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase

Journal Article · · Journal of Virology
DOI:https://doi.org/10.1128/JVI.02317-15· OSTI ID:1242301
 [1];  [2];  [3];  [2];  [1]
  1. Univ. of Alabama, Birmingham, AL (United States)
  2. Case Western Reserve Univ., Cleveland, OH (United States)
  3. Georgia State Univ., Atlanta, GA (United States)
+ Show Author Affiliations

Viruses have various mechanisms to duplicate their genomes and produce virus-specific mRNAs. Negative-strand RNA viruses encode their own polymerases to perform each of these processes. For the nonsegmented negative-strand RNA viruses, the polymerase is comprised of the large polymerase subunit (L) and the phosphoprotein (P). L proteins from members of the Rhabdoviridae, Paramyxoviridae, and Filoviridae share sequence and predicted secondary structure homology. Here, we present the structure of the N-terminal domain (conserved region I) of the L protein from a rhabdovirus, vesicular stomatitis virus, at 1.8-Å resolution. The strictly and strongly conserved residues in this domain cluster in a single area of the protein. Serial mutation of these residues shows that many of the amino acids are essential for viral transcription but not for mRNA capping. Three-dimensional alignments show that this domain shares structural homology with polymerases from other viral families, including segmented negative-strand RNA and double-stranded RNA (dsRNA) viruses. Negative-strand RNA viruses include a diverse set of viral families that infect animals and plants, causing serious illness and economic impact. Furthermore, the members of this group of viruses share a set of functionally conserved proteins that are essential to their replication cycle. Among this set of proteins is the viral polymerase, which performs a unique set of reactions to produce genome- and subgenome-length RNA transcripts. In this article, we study the polymerase of vesicular stomatitis virus, a member of the rhabdoviruses, which has served in the past as a model to study negative-strand RNA virus replication. We have identified a site in the N-terminal domain of the polymerase that is essential to viral transcription and that shares sequence homology with members of the paramyxoviruses and the filoviruses. Newly identified sites such as that described here could prove to be useful targets in the design of new therapeutics against negative-strand RNA viruses.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health (NIH); National Center for Research Resources, Biomedical Technology Program; National Inst. of General Medical Sciences
Grant/Contract Number:
W-31109-ENG-38
OSTI ID:
1242301
Journal Information:
Journal of Virology, Journal Name: Journal of Virology Journal Issue: 2 Vol. 90; ISSN 0022-538X
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (3)

Structure of the human metapneumovirus polymerase phosphoprotein complex journal November 2019
RNA Synthesis and Capping by Non-segmented Negative Strand RNA Viral Polymerases: Lessons From a Prototypic Virus journal July 2019
Transcriptional Control and mRNA Capping by the GDP Polyribonucleotidyltransferase Domain of the Rabies Virus Large Protein journal June 2019

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