Abstract
The rabies virus (RV) phosphoprotein P is a multifunctional protein involved in viral RNA synthesis and in counteracting host innate immune responses. We have previously shown that RV P gene expression levels can be regulated by using picornavirus internal ribosome entry site (IRES) elements. Here we exploited a particular feature of the foot-and-mouth disease virus (FMDV) IRES, namely, preferential initiation at a downstream initiation codon, to address the role of N-terminally truncated RV phosphoproteins usually generated in RV-infected cells through ribosomal leaky scanning. Recombinant RVs in which P synthesis was directed by the poliovirus or FMDV IRES produced full-length P (P1) or a truncated form (P2), as the dominant product, respectively. While the P2 overexpressing virus showed attenuated growth in interferon-incompetent cells, it was superior to the P1 overexpressing virus in preventing expression of host interferon-stimulated genes. This indicates that in RV infected cells the availability of the truncated P2 protein is critical for viral resistance to interferon.
Copyright © 2011 Elsevier GmbH. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line
-
Codon, Initiator / genetics
-
Cricetinae
-
DNA-Directed RNA Polymerases / genetics
-
Foot-and-Mouth Disease Virus / chemistry
-
Foot-and-Mouth Disease Virus / genetics
-
Genes, Reporter
-
Genetic Engineering / methods*
-
Genome, Viral*
-
Interferons / biosynthesis*
-
Interferons / immunology
-
Luciferases / analysis
-
Molecular Chaperones
-
Peptide Chain Initiation, Translational / genetics
-
Phosphoproteins / chemistry
-
Phosphoproteins / genetics*
-
Phosphoproteins / immunology
-
Phosphoproteins / metabolism
-
Plasmids
-
Poliovirus / chemistry
-
Poliovirus / genetics
-
Protein Biosynthesis*
-
Protein Isoforms / chemistry
-
Protein Isoforms / genetics*
-
Protein Isoforms / immunology
-
Protein Isoforms / metabolism
-
Rabies / immunology
-
Rabies / virology*
-
Rabies virus / genetics*
-
Rabies virus / immunology
-
Rabies virus / metabolism
-
Ribosomes / genetics
-
Ribosomes / metabolism
-
Transfection
-
Viral Proteins / genetics
-
Viral Structural Proteins / chemistry
-
Viral Structural Proteins / genetics*
-
Viral Structural Proteins / immunology
-
Viral Structural Proteins / metabolism
Substances
-
Codon, Initiator
-
Molecular Chaperones
-
P phosphoprotein, Rabies virus
-
Phosphoproteins
-
Protein Isoforms
-
Viral Proteins
-
Viral Structural Proteins
-
Interferons
-
Luciferases
-
bacteriophage T7 RNA polymerase
-
DNA-Directed RNA Polymerases