Induction of Porcine Dermatitis and Nephropathy Syndrome in Piglets by Infection with Porcine Circovirus Type 3

Abstract

Porcine circovirus type 3 (PCV3) is an emerging porcine circovirus that has been associated with porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs, reproductive failure, cardiac pathologies, and multisystemic inflammation in piglets and sows. Many aspects of PCV3 infection biology and pathogenesis, however, remain unknown. Here, we used a PCV3 virus stock from the rescue of an infectious PCV3 DNA clone to intranasally inoculate 4- and 8-week-old specific-pathogen-free piglets for evaluation of PCV3 pathogenesis. For 4-week-old piglets, typical clinical signs resembling those of PDNS-like disease were observed when piglets were inoculated with PCV3 alone or PCV3 combined with immunostimulation by keyhole limpet hemocyanin, with a mortality of 40% (2/5) for both types of inoculated piglets during a 28-day observation period postinoculation. Both types of inoculated piglets showed similar progressive increases in viral loads in the sera and had seroconverted to PCV3 capsid antibody after inoculation. Pathological lesions and PCV3-specific antigen were detected in various tissues and organs, including the lung, heart, kidney, lymph nodes, spleen, liver, and small intestine, in both types of inoculated piglets. The levels of proinflammatory cytokines and chemokines, including interleukin 1 beta (IL-1β), IL-6, IL-23α, gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and chemokine ligand 5 (CCL5), were significantly upregulated in both groups of inoculated piglets. Eight-week-old piglets also exhibited a similar PDNS-like disease but without death after PCV3 inoculation, as evidenced by pathological lesions and PCV3 antigen in various tissues and organs. These results show for the first time successful reproduction of PDNS-like disease by PCV3 infection and further provide significant information regarding the pathogenesis of PCV3 in piglets. IMPORTANCE Porcine circovirus type 3 (PCV3), an emerging porcine circovirus, is considered the cause of porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs and other systemic diseases in piglets and sows. To evaluate the pathogenesis of PCV3 infection in vivo, we used a PCV3 virus stock from the rescue of an infectious PCV3 DNA clone to intranasally inoculate 4- and 8-week-old specific-pathogen-free piglets and demonstrated successful reproduction of PDNS-like disease in animals that were inoculated with PCV3 alone or PCV3 combined with immunostimulation by keyhole limpet hemocyanin. Both 4- and 8-week-old PCV3-inoculated piglets showed similar increases in viral loads in the sera and had seroconverted to PCV3 capsid antibody. Pathological lesions and PCV3-specific antigen were detected in various tissues and organs, while numerous proinflammatory cytokines and chemokines in the sera were significantly upregulated after PCV3 inoculation. These results will provide significant information regarding the pathogenesis of PCV3 in piglets.

An epidemiological investigation of porcine circovirus 3 infection in dogs in the Guangxi Province from 2015 to 2017, China

“…T. Thaiwong hypothesizes that CPV-2 infection predisposed dogs to CaCV-1 infection and ultimately resulted in more severe diseases (Thaiwong et al, 2016). Multiple studies indicated that PCV3 is associated with multiple diseases in infected pigs (Jiang et al, 2019). Similar to PCV2, PCV3 also co-infects with other swine pathogens (such as PCV2, classical swine fever virus, PRRSV) Zheng et al, 2018).…”

“…Retrospective survey studies indicated that PCV3 infection could be traced back to 1996 . Recent studies confirmed that a PDNS-like disease is reproduced with PCV3 infection alone, and further research suggested that PCV3 is more pathogenic for piglets than PCV2 (Jiang et al, 2019).…”

Identification of Nuclear Localization Signals in the ORF2 Protein of Porcine Circovirus Type 3

“…PCV3 is associated with porcine dermatitis and nephropathy syndrome, congenital tremors, reproductive failure, and multi-systemic inflammation. PCV3 infection in piglets triggers inflammatory lesions in various tissues and organs followed by lymphocytic dysplasia and necrosis, and disruption of the immune system [20]. However, the exact pathogenesis of PCV3 remains unclear [21][22][23].…”

Reservoirs of Porcine Circoviruses: A Mini Review

“…In 2016, the third PCV, named PCV3, was discovered using high-throughput sequencing technology in U.S. swine herds suffering from porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure and other syndromes (11,12). A recent study suggested that PCV3 fulfilled Koch's postulates and could cause PDNS in piglets (13).…”