Effect of interferon-alpha on immediate early gene expression of murine cytomegalovirus.
Interferon-alpha (IFN-alpha) significantly reduced the replication of murine cytomegalovirus (MCMV) in mouse embryo fibroblasts derived from the susceptible mouse strain C3H/HeJ. When infectious virus production was measured, a strong decrease in virus titer was observed in IFN-treated cells at a multiplicity of infection (moi) of 1 and 0.5 pfu/cell. Analysis of virus-specified mRNAs by Northern blot assay revealed that IFN-alpha had a significant effect on the expression of viral mRNAs at 48h. In particular, the mRNAs of the major immediate early (IE) transcription units, IE1, IE2, and IE3, were impaired by IFN-alpha. In addition, decrease of IE1 mRNA synthesis was accompanied by a reduction of the major IE product (pp89), as revealed by Western blot assay. These results suggest that IFN-alpha may inhibit MCMV replication by directly impairing IE gene transcription.
Institute of Microbiology, School of Medicine, University of Turin, Italy.
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MG
Martinotti
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Gribaudo
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Gariglio
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A
Caliendo
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Lembo
A
A
Angeretti
R
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Cavallo
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Landolfo
D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D017874:Immediate-Early Proteins / Q000235:genetics*; D016898:Interferon-alpha / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000096:biosynthesis; D015534:Trans-Activators; D014158:Transcription, Genetic / Q000187:drug effects*; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000187:drug effects / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
C088645:IE1 protein, cytomegalovirus; C069186:IE2 protein, Cytomegalovirus; C088646:IE3 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D015534:Trans-Activators; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus