Saikia Paramananda, Gopinath M, Shaila M S
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.
Arch Virol. 2008;153(4):615-26. doi: 10.1007/s00705-008-0034-9. Epub 2008 Jan 29.
The phosphoprotein P of paramyxoviruses is known to play more than one role in genome transcription and replication. Phosphorylation of P at the NH(2) terminus by cellular casein kinase II has been shown to be necessary for transcription of the genome in some of the viruses, while it is dispensable for replication. The phosphorylation null mutant of rinderpest virus P protein, in which three serine residues have been mutated, has been shown earlier to be non-functional in an in vivo minigenome replication/transcription system. In this work, we have shown that the phosphorylation of P protein is essential for transcription, whereas the null mutant is active in replication of the genome in vivo. The null mutant P acts as a transdominant repressor of transcriptional activity of wild-type P and as an activator of replication carried out by wild-type P protein. These results suggest the phosphorylation status of P may act as a replication switch during virus replication. We also show that the phosphorylation null mutant P is capable of interacting with L and N proteins and is able to form a tripartite complex of L-(N-P) when expressed in insect cells, similar to wild-type P protein.
副粘病毒的磷蛋白P在基因组转录和复制中发挥多种作用。细胞酪蛋白激酶II对P蛋白氨基末端的磷酸化已被证明对某些病毒的基因组转录是必需的，而对复制则是可有可无的。牛瘟病毒P蛋白的磷酸化缺失突变体（其中三个丝氨酸残基已发生突变）先前已被证明在体内微型基因组复制/转录系统中无功能。在这项研究中，我们表明P蛋白的磷酸化对转录至关重要，而缺失突变体在体内基因组复制中具有活性。缺失突变体P作为野生型P转录活性的反式显性抑制剂，并作为野生型P蛋白进行复制的激活剂。这些结果表明，P的磷酸化状态可能在病毒复制过程中充当复制开关。我们还表明，磷酸化缺失突变体P能够与L蛋白和N蛋白相互作用，并且当在昆虫细胞中表达时能够形成L-(N-P)三方复合物，类似于野生型P蛋白。
