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Replication of porcine circoviruses.

Faurez F, Dory D, Grasland B, Jestin A - Virol. J. (2009)

Bottom Line: Porcine circovirus type 1 is non pathogenic contrary to porcine circovirus type 2 which is associated with the disease known as Post-weaning Multisystemic Wasting Syndrome.Porcine circovirus replication probably involves a "melting pot" rather than "cruciform" rolling-circle mechanism.This review provides a summary of current knowledge of replication in porcine circoviruses as models of the Circovirus genus.Based on various studies, the factors affecting replication are defined and the mechanisms involved in the different phases of replication are described or proposed.

View Article: PubMed Central - HTML - PubMed

Affiliation: French Food Safety Agency, Viral Genetics and Biosafety Unit, Ploufragan, France. f.faurez@afssa.fr

ABSTRACT
Porcine circoviruses are circular single-stranded DNA viruses that infect swine and wild boars. Two species of porcine circoviruses exist. Porcine circovirus type 1 is non pathogenic contrary to porcine circovirus type 2 which is associated with the disease known as Post-weaning Multisystemic Wasting Syndrome. Porcine circovirus DNA has been shown to replicate by a rolling circle mechanism. Other studies have revealed similar mechanisms of rolling-circle replication in plasmids and single-stranded viruses such as Geminivirus. Three elements are important in rolling-circle replication: i) a gene encoding initiator protein, ii) a double strand origin, and iii) a single strand origin. However, differences exist between viruses and plasmids and between viruses. Porcine circovirus replication probably involves a "melting pot" rather than "cruciform" rolling-circle mechanism.This review provides a summary of current knowledge of replication in porcine circoviruses as models of the Circovirus genus. Based on various studies, the factors affecting replication are defined and the mechanisms involved in the different phases of replication are described or proposed.

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Model of the termination of rolling circle replication described by Novick in the nineties. Black: parental strand; Red: newly synthesized strand; Blue: newly synthesized strand during a second round of replication. Step 1: After the first round of replication, the REP complex bound on the 5' end would be situated behind the generated stem-loop. Step 2: the tyrosine (Y) of the unused sub-unit during the initiation might cleave the regenerated replication origin. It will (then bind to the 5' end of the newly synthesized strand. Step 3: the 3'OH free end generated during step 2 and belonging to the parental strand might then exert a nucleophilic attack on the tyrosylphosphodiester bridge generated during the initiation step. This reaction would lead to the release of a single stranded DNA. Step 4: the tyrosine previously involved in initiation of the replication attacks the cutting site of the newly synthesized strand. This reaction would generate a free 3'OH on the newly synthesized strand and a tyrosylphosphodiester bridge with a 12 mers oligonucleotide. Steps 5 and 6: the free 3'OH generated at step 4 can attack the tyrosylphosphodiester bridge generated at step 2, that would close the double stranded DNA and release an inactivated Rep homodimer due to the binding of one tyrosine to one oligonucleotide. Adapted from Microbiology and Molecular Biology Reviews 62(2), del Solar G et al, "Replication and control of circular bacterial plasmids." pages 434–464, Copyright© 1998 [5], with permission from American Society for Microbiology.
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Figure 6: Model of the termination of rolling circle replication described by Novick in the nineties. Black: parental strand; Red: newly synthesized strand; Blue: newly synthesized strand during a second round of replication. Step 1: After the first round of replication, the REP complex bound on the 5' end would be situated behind the generated stem-loop. Step 2: the tyrosine (Y) of the unused sub-unit during the initiation might cleave the regenerated replication origin. It will (then bind to the 5' end of the newly synthesized strand. Step 3: the 3'OH free end generated during step 2 and belonging to the parental strand might then exert a nucleophilic attack on the tyrosylphosphodiester bridge generated during the initiation step. This reaction would lead to the release of a single stranded DNA. Step 4: the tyrosine previously involved in initiation of the replication attacks the cutting site of the newly synthesized strand. This reaction would generate a free 3'OH on the newly synthesized strand and a tyrosylphosphodiester bridge with a 12 mers oligonucleotide. Steps 5 and 6: the free 3'OH generated at step 4 can attack the tyrosylphosphodiester bridge generated at step 2, that would close the double stranded DNA and release an inactivated Rep homodimer due to the binding of one tyrosine to one oligonucleotide. Adapted from Microbiology and Molecular Biology Reviews 62(2), del Solar G et al, "Replication and control of circular bacterial plasmids." pages 434–464, Copyright© 1998 [5], with permission from American Society for Microbiology.

Mentions: A termination model of rolling circle replication based on pT181 plasmid studies was described in the nineties by Novick's team [30]. This mechanism is based on nucleophilic attacks on a tyrosylphosphodiester bond by a free 3'OH and on catalytic activity of a tyrosine on the DNA (figure 6). This leads to the release of a covalently closed circular single-strand DNA, a covalently closed circular double-strand DNA and an inactivated Rep heterodimer. The inactivated Rep heterodimer might result from binding of the tyrosylphosphodiester in a 12-mers oligonucleotide to one of the Rep proteins (figure 6, step 6). This oligonucleotide comes from the newly synthesized strand which is slightly more than one genome unit long (figure 6, step 4).


Replication of porcine circoviruses.

Faurez F, Dory D, Grasland B, Jestin A - Virol. J. (2009)

Model of the termination of rolling circle replication described by Novick in the nineties. Black: parental strand; Red: newly synthesized strand; Blue: newly synthesized strand during a second round of replication. Step 1: After the first round of replication, the REP complex bound on the 5' end would be situated behind the generated stem-loop. Step 2: the tyrosine (Y) of the unused sub-unit during the initiation might cleave the regenerated replication origin. It will (then bind to the 5' end of the newly synthesized strand. Step 3: the 3'OH free end generated during step 2 and belonging to the parental strand might then exert a nucleophilic attack on the tyrosylphosphodiester bridge generated during the initiation step. This reaction would lead to the release of a single stranded DNA. Step 4: the tyrosine previously involved in initiation of the replication attacks the cutting site of the newly synthesized strand. This reaction would generate a free 3'OH on the newly synthesized strand and a tyrosylphosphodiester bridge with a 12 mers oligonucleotide. Steps 5 and 6: the free 3'OH generated at step 4 can attack the tyrosylphosphodiester bridge generated at step 2, that would close the double stranded DNA and release an inactivated Rep homodimer due to the binding of one tyrosine to one oligonucleotide. Adapted from Microbiology and Molecular Biology Reviews 62(2), del Solar G et al, "Replication and control of circular bacterial plasmids." pages 434–464, Copyright© 1998 [5], with permission from American Society for Microbiology.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 6: Model of the termination of rolling circle replication described by Novick in the nineties. Black: parental strand; Red: newly synthesized strand; Blue: newly synthesized strand during a second round of replication. Step 1: After the first round of replication, the REP complex bound on the 5' end would be situated behind the generated stem-loop. Step 2: the tyrosine (Y) of the unused sub-unit during the initiation might cleave the regenerated replication origin. It will (then bind to the 5' end of the newly synthesized strand. Step 3: the 3'OH free end generated during step 2 and belonging to the parental strand might then exert a nucleophilic attack on the tyrosylphosphodiester bridge generated during the initiation step. This reaction would lead to the release of a single stranded DNA. Step 4: the tyrosine previously involved in initiation of the replication attacks the cutting site of the newly synthesized strand. This reaction would generate a free 3'OH on the newly synthesized strand and a tyrosylphosphodiester bridge with a 12 mers oligonucleotide. Steps 5 and 6: the free 3'OH generated at step 4 can attack the tyrosylphosphodiester bridge generated at step 2, that would close the double stranded DNA and release an inactivated Rep homodimer due to the binding of one tyrosine to one oligonucleotide. Adapted from Microbiology and Molecular Biology Reviews 62(2), del Solar G et al, "Replication and control of circular bacterial plasmids." pages 434–464, Copyright© 1998 [5], with permission from American Society for Microbiology.
Mentions: A termination model of rolling circle replication based on pT181 plasmid studies was described in the nineties by Novick's team [30]. This mechanism is based on nucleophilic attacks on a tyrosylphosphodiester bond by a free 3'OH and on catalytic activity of a tyrosine on the DNA (figure 6). This leads to the release of a covalently closed circular single-strand DNA, a covalently closed circular double-strand DNA and an inactivated Rep heterodimer. The inactivated Rep heterodimer might result from binding of the tyrosylphosphodiester in a 12-mers oligonucleotide to one of the Rep proteins (figure 6, step 6). This oligonucleotide comes from the newly synthesized strand which is slightly more than one genome unit long (figure 6, step 4).

Bottom Line: Porcine circovirus type 1 is non pathogenic contrary to porcine circovirus type 2 which is associated with the disease known as Post-weaning Multisystemic Wasting Syndrome.Porcine circovirus replication probably involves a "melting pot" rather than "cruciform" rolling-circle mechanism.This review provides a summary of current knowledge of replication in porcine circoviruses as models of the Circovirus genus.Based on various studies, the factors affecting replication are defined and the mechanisms involved in the different phases of replication are described or proposed.

View Article: PubMed Central - HTML - PubMed

Affiliation: French Food Safety Agency, Viral Genetics and Biosafety Unit, Ploufragan, France. f.faurez@afssa.fr

ABSTRACT
Porcine circoviruses are circular single-stranded DNA viruses that infect swine and wild boars. Two species of porcine circoviruses exist. Porcine circovirus type 1 is non pathogenic contrary to porcine circovirus type 2 which is associated with the disease known as Post-weaning Multisystemic Wasting Syndrome. Porcine circovirus DNA has been shown to replicate by a rolling circle mechanism. Other studies have revealed similar mechanisms of rolling-circle replication in plasmids and single-stranded viruses such as Geminivirus. Three elements are important in rolling-circle replication: i) a gene encoding initiator protein, ii) a double strand origin, and iii) a single strand origin. However, differences exist between viruses and plasmids and between viruses. Porcine circovirus replication probably involves a "melting pot" rather than "cruciform" rolling-circle mechanism.This review provides a summary of current knowledge of replication in porcine circoviruses as models of the Circovirus genus. Based on various studies, the factors affecting replication are defined and the mechanisms involved in the different phases of replication are described or proposed.

Show MeSH
Related in: MedlinePlus