Inhibition of human parainfluenza virus-3 replication by interferon and human MxA.
We have investigated the IFN-mediated inhibition of human parainfluenza virus-3 (HPIV-3) replication in cultured human A549 cells. IFN-alpha inhibited the virus yield significantly with concomitant reduction of viral RNA accumulation by more than 90%. Further studies indicated that the inhibitory action of IFN was at the level of primary transcription of HPIV3 replication. Since the IFN-inducible protein, MxA, has been shown to inhibit virus replication in several RNA viruses, we examined the role of MxA in HPIV-3 replication using a stably transfected human glioblastoma cell line expressing MxA. In these cells HPIV-3 replication was decreased by more than 100-fold depending on the virus dosage used with concomitant inhibition of viral RNA synthesis by about 80%. However, the viral primary transcription was not affected in this MxA-producing cell line. In contrast, in the parental cell line IFN-mediated inhibition occurred at the primary transcription step of HPIV-3 replication. These data suggest that in addition to MxA, other IFN-inducible proteins are involved in the anti-HPIV-3 effect of IFN in both the cell lines used.
Zhao
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Department of Molecular Biology Research Institute, Cleveland Clinic Foundation, Ohio 44195, USA.
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Das
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Banerjee
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D000998:Antiviral Agents / Q000096:biosynthesis / Q000494:pharmacology*; D019204:GTP-Binding Proteins; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008561:Membrane Fusion / Q000187:drug effects; D064547:Myxovirus Resistance Proteins; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology*; D012367:RNA, Viral / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D012367:RNA, Viral; D019204:GTP-Binding Proteins