Author
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Cheung, Andrew |
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Submitted to: Virology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/5/2015 Publication Date: 7/1/2015 Citation: Cheung, A.K. 2015. Specific functions of the Rep and Rep' proteins of porcine circovirus during copy-release and rolling-circle DNA replication. Virology. 481:43-50. Interpretive Summary: The method by which some viruses replicate their genome, called rolling circle replication, has been proposed for some time; however, the specific mechanisms of how this occurs still have not been clarified. In this work the mechanism involved to ensure the perpetual replication of porcine circovirus, which uses rolling circle replication to generate more copies of its DNA, was delineated. It is important to know the specific mechanics of virus replication in order to be able to intervene in the infectious process. This not only has implications for porcine circovirus, which causes losses to the swine industry, but to other biological systems that use the rolling circle mechanism of replication. Technical Abstract: The roles of two porcine circovirus replication initiator proteins, Rep and Rep', in generating copy-release and rolling-circle DNA replication intermediates were determined. Rep uses the supercoiled closed-circular genome (ccc) to initiate leading-strand synthesis (identical to copy-release replication) and generates the single-stranded circular (ssc) genome from the displaced DNA strand. In the process, a minus-genome primer (MGP) necessary for complementary-strand synthesis, from ssc to ccc, is synthesized. Rep' cleaves the growing nascent-strand to regenerate the parent ccc molecule. In the process, a Rep'-DNA hybrid containing the right palindromic sequence (at the origin of DNA replication) is generated. Analysis of the virus particle showed that it is composed of four components: ssc, MGP, capsid protein and a novel Rep-related protein (designated Protein-3). |
