Abstract
BackgroundNorovirus genomic and subgenomic RNAs are covalently linked at the 5' nucleotide to a 15 kD protein called VPg. VPg of two human norovirus strains binds translation initiation factor eIF3 and other eIFs in vitro, suggesting VPg functions in initiation of protein synthesis on viral RNA. Human norovirus strains are not cultivable, and thus experimental evidence of interactions between VPg and eIFs in infected cells has been lacking. We used the cultivable murine norovirus MNV-1 as a model to study interactions between VPg and eIFs in infected cells.ResultsAs shown previously for human norovirus VPg, MNV-1 VPg bound eIF3, eIF4GI, eIF4E, and S6 ribosomal protein in cell extracts by GST pull-down assay. Importantly, MNV-1 VPg co-precipitated eIF4GI and eIF4E from infected macrophages, providing evidence that VPg interacts with components of the translation machinery in norovirus infected cells.ConclusionThe interactions between MNV-1 VPg and eIFs completely mimic those reported for the human norovirus VPg, illustrating the utility of MNV-1 as a relevant molecular model to study mechanisms of human norovirus replication.
Highlights
Norovirus genomic and subgenomic RNAs are covalently linked at the 5' nucleotide to a 15 kD protein called VPg
The linkage between VPg and the 5' nucleotide has been demonstrated experimentally only for the animal caliciviruses [2,3], but by analogy, it is assumed that VPg is linked to norovirus genomes
Studies of animal caliciviruses showed VPg is necessary for infectivity of native viral RNA [2], but an m7G cap can confer infectivity to in vitro synthesized feline calicivirus (FCV) genomic RNA transcripts [4]
Summary
Norovirus genomic and subgenomic RNAs are covalently linked at the 5' nucleotide to a 15 kD protein called VPg. ORF2 and ORF3 encode the capsid protein VP1 and minor structural protein VP2, respectively Both VP1 and VP2 are synthesized from a subgenomic RNA that is 3' coterminal with the genomic RNA. Studies of animal caliciviruses showed VPg is necessary for infectivity of native viral RNA [2], but an m7G cap can confer infectivity to in vitro synthesized feline calicivirus (FCV) genomic RNA transcripts [4]. Together, data from these studies conclude that the m7G cap functionally substitutes for VPg when transfecting calicivirus RNA into cells.
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