Detection of a novel circovirus PCV3 in pigs with cardiac and multi-systemic inflammation

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Detection of a novel circovirus PCV3 in pigs with cardiac and multi-systemic inflammation Tung Gia Phan1,2, Federico Giannitti3,4, Stephanie Rossow3, Douglas Marthaler3, Todd Knutson3, Linlin Li1,2, Xutao Deng1, Talita Resende3, Fabio Vannucci3 and Eric Delwart1,2*

Abstract Background: Porcine circovirus 2 causes different clinical syndromes resulting in a significant economic loss in the pork industry. Three pigs with unexplained cardiac and multi-organ inflammation that tested negative for PCV2 and other known porcine pathogens were further analyzed. Methods: Histology was used to identify microscopic lesions in multiple tissues. Metagenomics was used to detect viral sequences in tissue homogenates. In situ hybridization was used to detect viral RNA expression in cardiac tissue. Results: In all three cases we characterized the genome of a new circovirus we called PCV3 with a replicase and capsid proteins showing 55 and 35 % identities to the genetically-closest proteins from a bat-feces associated circovirus and were even more distant to those of porcine circovirus 1 and 2. Common microscopic lesions included non-suppurative myocarditis and/or cardiac arteriolitis. Viral mRNA was detected intralesionally in cardiac cells. Deep sequencing in tissues also revealed the presence of porcine astrovirus 4 in all three animals as well as rotavirus A, porcine cytomegalovirus and porcine hemagglutinating encephalomyelitis virus in individual cases. Conclusion: The pathogenicity and molecular epidemiology of this new circovirus, alone or in the context of co-infections, warrants further investigations. Keywords: Arteriolitis, Circovirus, Myocarditis, Pig, Vasculitis, Metagenomics

The study Circoviruses are small viruses with circular singlestranded DNA genomes of ≈ 2 kb belonging to the family Circoviridae and are associated with a wide spectrum of illnesses in pigs, birds, dogs and foxes [1–5]. There are only two circovirus species reported in pigs, namely the closely related porcine circovirus types 1 and 2 (PCV1 and 2); however, only PCV2 infection is known to cause clinical disease manifested by reproductive, respiratory, renal, enteric, lymphatic, cardiovascular, nervous, and/or skin disorders, resulting in significant economic losses to pork producers [1, 6]. Several divergent circovirus genomes have been also detected * Correspondence: [email protected] 1 Blood Systems Research Institute, San Francisco, CA 94118, USA 2 Department of Laboratory Medicine, University of California at San Francisco, San Francisco, CA 94118, USA Full list of author information is available at the end of the article

in human feces, bats, mink and fish [7–10]. Here we report infections with a novel circovirus we called PCV3 in three pigs with cardiac pathology and multisystemic inflammation. Case 1

A group of 1000 pigs from a commercial operation in Missouri included 2 % of animals which showed clinical disease of anorexia, weight loss and swollen joints beginning at approximately 1 week post-weaning.