CpG distribution and methylation pattern in porcine parvovirus

Area of Science:

• Virology
• Genomics
• Epigenetics

Background:

• Parvovirinae subfamily members can be classified into three groups based on GC content and CpG observed/expected ratio (oCpGr).
• Porcine parvovirus (PPV) is a Group I parvovirus characterized by low GC content, low oCpGr, and an ascending CpG distribution in coding regions.

Purpose of the Study:

• To investigate the methylation status of the PPV genome throughout its lifecycle.
• To determine the effect of CpG methylation on PPV replication and the role of DNA methyltransferases in this process.
• To explore factors contributing to the low CpG site frequency in the PPV genome.

Main Methods:

• Analysis of GC content and observed/expected CpG ratio (oCpGr) for parvovirus classification.
• In vitro CpG methylation assays to assess its effect on PPV replication.
• Investigation of DNA methyltransferase (DNMT) activity and PPV infection.
• Single Nucleotide Polymorphism (SNP) analysis of PPV genomes.

Main Results:

• The entire PPV genome remains hypomethylated during its lifecycle, irrespective of tissue origin.
• In vitro CpG methylation shows a modest inhibitory effect on PPV replication, but hypermethylation is lost during replication.
• PPV infection does not affect DNA methyltransferase expression, translation, or localization.
• High mutability of CpG sites was observed in PPV genomes, and introducing extra CpG sites had no significant biological effect on replication.

Conclusions:

• The PPV genome is resistant to effective methylation by DNMT1, DNMT3a, and DNMT3b during replication.
• Both natural selection and mutational pressure may contribute to the low frequency of CpG sites in the PPV genome.