PMID- 21865380 OWN - NLM STAT- MEDLINE DCOM- 20111121 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 85 IP - 21 DP - 2011 Nov TI - Coreplication of the major genotype group members of porcine circovirus type 2 as a prerequisite to coevolution may explain the variable disease manifestations. PG - 11111-20 LID - 10.1128/JVI.05156-11 [doi] AB - A member of the family Circoviridae, porcine circovirus type 2 (PCV2), is associated with postweaning multisystemic wasting syndrome (PMWS), a recent emerging disease worldwide. PCV2 is also found in clinically 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 tissues from subclinically infected and diseased piglets. We compared antigen- and PCV2 DNA-derived signals for tissue localization and intensity. Oligonucleotides were designed 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). Unexpectedly, all PCV2-infected animals carried both PCV2a and PCV2b genotype group members. Using confocal microscopy, genotype single-cell infections and cell superinfections were visible. Additionally, we discriminated replicative DNA from total PCV2 DNA isoforms with FISH. This aided in our inquiry into cellular genotype-specific replication. Importantly, single-genotype-group replication was not observed. In infected cells with replicating virus, both genotype groups were equally present. These findings suggest PCV2 genotype group members relaxed replication regulation requirements and may even point to PCV2 replication cooperativity in vivo. These observations explain the readily seen PCV2 DNA recombinations and the high overall PCV2 genome plasticity. Hence, we suggest a novel mechanism of syndrome etiology that consists of a continuously changing PCV2 genome pool in hosts and pig herds, posing a constant challenge to the individual maturing immune system. FAU - Khaiseb, Siegfried AU - Khaiseb S AD - Institute of Veterinary Pathology, University of Zurich, Vetsuisse Faculty, Zurich, Switzerland. FAU - Sydler, Titus AU - Sydler T FAU - Zimmermann, Dieter AU - Zimmermann D FAU - Pospischil, Andreas AU - Pospischil A FAU - Sidler, Xaver AU - Sidler X FAU - Brugnera, Enrico AU - Brugnera E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110824 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Capsid Proteins) RN - 0 (DNA, Viral) SB - IM MH - Animals MH - Capsid Proteins/genetics MH - Circovirus/classification/genetics/*growth & development/*pathogenicity MH - DNA, Viral/genetics MH - *Evolution, Molecular MH - Genotype MH - In Situ Hybridization MH - Microscopy, Confocal MH - Polymerase Chain Reaction MH - Porcine Postweaning Multisystemic Wasting Syndrome/*virology MH - Swine MH - *Virus Replication PMC - PMC3194933 EDAT- 2011/08/26 06:00 MHDA- 2011/12/13 00:00 PMCR- 2012/05/01 CRDT- 2011/08/26 06:00 PHST- 2011/08/26 06:00 [entrez] PHST- 2011/08/26 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2012/05/01 00:00 [pmc-release] AID - JVI.05156-11 [pii] AID - 5156-11 [pii] AID - 10.1128/JVI.05156-11 [doi] PST - ppublish SO - J Virol. 2011 Nov;85(21):11111-20. doi: 10.1128/JVI.05156-11. Epub 2011 Aug 24.