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Background

Type I interferons (IFN) include multiple IFN-alpha subtypes which exhibit considerable amino acid identity and activate the same cell-surface receptor. The promoter regions of the IFN-alpha genes, however, have different transcription factor binding sites, implying differential transcriptional activation. Evolutionary conservation of multiple subtypes may have resulted from external pressures associated with the crucial nature of an IFN response, namely that different viruses that are tropic for different target tissues determine the nature and extent of an IFN response, specifically the IFN-alpha subtype profile.

Methods

Studies were undertaken to examine inducible IFN gene expression profiles in response to infection with single-stranded RNA viruses: Sendai virus (SeV), murine hepatitis virus (MHV-1) and coxsackie virus B3 (CVB3).

Results

In vitro, distinct signature profiles of SeV and MHV-1-inducible gene expression for IFN-alpha2, IFN-alpha4 and IFN-alpha5 subtypes in L2 and L929 mouse fibroblast cells, in relation to the extent and kinetics of their induction, were identified. In vivo, whereas A/J mice are highly permissive for both MHV-1 and CVB3 infections and mount a poor IFN response, C57B1/6 mice are relatively resistant to both virus infections and mount a vigorous IFN response.

Conclusions

These data suggest that the infecting virus and the target cell type dictate the extent and signature of inducible type I IFN gene expression. The extent of IFN response to viral infection influences the subsequent biological outcome: a robust IFN response prescribes a level of resistance, whereas a poor IFN response contributes towards a permissive phenotype for infection."xsd:string
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http://purl.uniprot.org/citations/18572754http://purl.uniprot.org/core/author"Fish E.N."xsd:string
http://purl.uniprot.org/citations/18572754http://purl.uniprot.org/core/author"Baig E."xsd:string
http://purl.uniprot.org/citations/18572754http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18572754http://purl.uniprot.org/core/name"Antivir Ther"xsd:string
http://purl.uniprot.org/citations/18572754http://purl.uniprot.org/core/pages"409-422"xsd:string
http://purl.uniprot.org/citations/18572754http://purl.uniprot.org/core/title"Distinct signature type I interferon responses are determined by the infecting virus and the target cell."xsd:string
http://purl.uniprot.org/citations/18572754http://purl.uniprot.org/core/volume"13"xsd:string
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