Comparative immunopathogenesis and biology of recently discovered
porcine circoviruses
Abstract
Porcine circoviruses are important pathogens of production swine.
Porcine circovirus type 1 (PCV1) is non-pathogenic, and discovered as a
contaminant of a porcine kidney cell line, PK-15. The discovery of
pathogenic variant, PCV2, occurred in the late 90’s in association with
post-weaning multi-systemic wasting disease syndrome (PMWS), which is
characterized by wasting, respiratory signs and lymphadenopathy in
weanling pigs. A new PCV type, designated as PCV3, was discovered in
2016, in pigs manifesting porcine dermatitis and nephropathy syndrome
(PDNS), respiratory distress and reproductive failure. Pathological
manifestations of PCV3 Infections include systemic inflammation,
vasculitis and myocarditis. A 4 th PCV type, PCV4, was
identified in 2020 in pigs with PDNS, respiratory and enteric signs. All
the pathogenic PCV types are detected in both healthy and morbid pigs.
They cause chronic, systemic infections with various clinical
manifestations. Dysregulation of the immune system homeostasis is a
pivotal trigger for pathogenesis in porcine circoviral infections. While
the study of PCV3 immunobiology is still in its infancy lessons learned
from PCV2 and other circular replication-associated protein
(Rep)-encoding single stranded(ss) (CRESS) DNA viruses can inform the
field of exploration for PCV3. Viral interactions with the innate immune
system, interference with dendritic cell function coupled with the
direct loss of lymphocytes compromises both innate and adaptive immunity
in PCV2 infections. Dysregulated immune responses leading to the
establishment of a pro-inflammatory state, immune complex associated
hypersensitivity, and the necrosis of lymphocytes and immune cells are
key features of PCV3 immunopathogenesis. A critical overview of the
comparative immunopathology of PCV2 and PCV3/4, and directions for
future research in the field are presented in this review.