Genetic and biochemical evidence for an oligomeric structure of the functional L polymerase of the prototypic arenavirus lymphocytic choriomeningitis virus.
J Virol
; 79(11): 7262-8, 2005 Jun.
Article
in En
| MEDLINE
| ID: mdl-15890965
ABSTRACT
The arenavirus L protein has the characteristic sequence motifs conserved among the RNA-dependent RNA polymerase L proteins of negative-strand (NS) RNA viruses. Studies based on the use of reverse-genetics approaches have provided direct experimental evidence of the key role played by the arenavirus L protein in viral-RNA synthesis. Sequence alignment shows six conserved domains among L proteins of NS RNA viruses. The proposed polymerase module of L is located within its domain III, which contains highly conserved amino acids within motifs designated A and C. We have examined the role of these conserved residues in the polymerase activity of the L protein of the prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), in vivo using a minigenome rescue assay. We show here that the presence of sequence SDD, a characteristic of motif C of segmented NS RNA viruses, as well as the presence of the highly conserved D residue within motif A of L proteins, is strictly required for the polymerase activity of the LCMV L protein. The strong dominant negative phenotype associated with many of the mutants examined and results from coimmunoprecipitation studies provided genetic and biochemical evidence, respectively, for the requirement of the L-L interaction for the polymerase activity of the LCMV L protein.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Viral Proteins
/
RNA-Dependent RNA Polymerase
/
Lymphocytic choriomeningitis virus
Limits:
Animals
Language:
En
Journal:
J Virol
Year:
2005
Document type:
Article
Affiliation country:
United States