Cellular protein kinase C isoform zeta regulates human parainfluenza virus type 3 replication.
Phosphorylation of the P proteins of nonsegmented negative-strand RNA viruses is critical for their function as transactivators of the viral RNA polymerases. Using unphosphorylated P protein of human parainfluenza virus type 3 (HPIV3) expressed in Escherichia coli, we have shown that the cellular protein kinase that phosphorylates P in vitro is biochemically and immunologically indistinguishable from cellular protein kinase C isoform zeta (PKC-zeta). Further, PKC-zeta is specifically packaged within the progeny HPIV3 virions and remains tightly associated with the ribonucleoprotein complex. The P protein seems also to be phosphorylated intracellularly by PKC-zeta, as shown by the similar protease digestion pattern of the in vitro and in vivo phosphorylated P proteins. The growth of HPIV3 in CV-1 cells is completely abrogated when a PKC-zeta-specific inhibitor pseudosubstrate peptide was delivered into cells. These data indicate that PKC-zeta plays an important role in HPIV3 gene expression by phosphorylating P protein, thus providing an opportunity to develop antiviral agents against an important human pathogen.
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Department of Molecular Biology, Cleveland Clinic Foundation, OH 44195, USA.
Gupta
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Gupta
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Banerjee
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D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004926:Escherichia coli; D005814:Genes, Viral; D006801:Humans; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000502:physiology*; D010449:Peptide Mapping; D010766:Phosphorylation; D011493:Protein Kinase C / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism*; D013379:Substrate Specificity; D014764:Viral Proteins / Q000096:biosynthesis / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
D007527:Isoenzymes; D011994:Recombinant Proteins; D014764:Viral Proteins; D011493:Protein Kinase C