Porcine circovirus 2 genotype groups and subgenotypes co-replication a major contributing factor to disease riddle?

Abstract

A Circoviridae family member, porcine circovirus type 2 (PCV2), is associated with postweaning multisystemic wasting syndrome (PMWS), a recent emerging disease worldwide. PCV2 is also found in clinical asymptomatic animals. This paradoxical finding makes the syndrome etiology challenging. We developed new assays to study PCV2 with links to syndrome etiology. For analysis we used PCV2 infected tissue from subclinical infected and diseased piglets. We compared antigen and PCV2 DNA derived signals in tissue localization and intensity. We designed oligonucleotides to the signature motif of the PCV2 capsid open reading frame to discriminate experimentally between PCV2 genotype groups by PCR, in situ hybridization (ISH) and fluorescence in situ hybridization (FISH). With genotypic PCR and ISH, we found PCV2 infected animals to carry both PCV2a and PCV2b genotype groups. We observed genotype single cell infection and superinfections by both genotype groups. By FISH, we discriminated replicative DNA isoform from total PCV2 DNA isoforms. We extended this method to inquire genotype group specific replication. Single genotype group replication was not observed. These findings suggest PCV2 genotype relaxed replication regulation requirements and, may even point to genotype group replication cooperativity in vivo. These observations explain the readily seen PCV2 DNA recombination and the high overall PCV2 genome plasticity. We propose a novel mechanism for syndrome ethiology.