title: Latent porcine circovirus type 2-infected domestic pigs: A potential infection model for the effective development of vaccines against latent or chronic virus induced diseases.
abstract: Until recently, knowledge of the pathogenicity of Circoviridae and Anelloviridae family members was limited. Our previous discoveries provided clues toward resolving this issue based on studies of the latent nature of porcine circovirus type 2 (PCV2) genotype group members. We developed a conventional pig infection model that indicated that weaners already harbored latent PCV2 infection in the thymus, which enabled the viruses to specifically modulate the maturation of T-helper cells. This finding raised the possibility that the thymi of normal fetuses were already infected with PCV2. The present findings further substantiate our hypothesis that PCV2 masquerades as the host by infecting fetuses before they acquire immune-competence. We provide the first demonstration that all domestic pig fetuses preferentially harbor latent PCV2-infected cells in their thymi. These PCV2-infected cells are different from thymocytes and are located in the medulla of the fetal thymus. These latent PCV2-infected cells in fetuses are found at the same location and share characteristics with the infected cells observed in adolescent pigs. Moreover, fetuses also harbor these infected cells in other lymph system organs. We provide the first demonstration that the fetal thymus virus pools are minimally affected by sow vaccination, highlighting the immune-privileged character of this organ. Furthermore, we found a striking reduction in virus-infected cells in the fetal spleen and an increase in PCV2-infected cells in the fetal intestine of anti-PCV2-vaccinated mothers. These data indicate that specific immune response interactions occur between mothers and their progeny that are not dependent on the humoral immunity of the mother and cannot be attributed to the rudimentary humoral responses of the fetuses because these pig fetuses do not have any PCV2-specific antibodies. These shifts in our understanding of the PCV2-infected cell pool will lead to different avenues in the search for effective vaccination strategies against latent and chronic pathogens.
authors.affiliation: Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: Titus
authors.initials: T
authors.lastname: Sydler
authors.affiliation: Division of Swine Medicine of the Department for Farm Animals, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Brägger
authors.affiliation: Division of Swine Medicine of the Department for Farm Animals, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Handke
authors.affiliation: Division of Veterinary Epidemiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hartnack
authors.affiliation: Division of Veterinary Epidemiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: Fraser I
authors.initials: FI
authors.lastname: Lewis
authors.affiliation: Division of Swine Medicine of the Department for Farm Animals, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
authors.forename: Xaver
authors.initials: X
authors.lastname: Sidler
authors.affiliation: Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Division of Swine Medicine of the Department for Farm Animals, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. Electronic address: enbrug@vetpath.uzh.ch.
authors.forename: Enrico
authors.initials: E
authors.lastname: Brugnera
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018173:Circoviridae Infections / Q000473:pathology / Q000517:prevention & control / Q000662:veterinary*; D017925:Circovirus; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D018445:Infectious Disease Transmission, Vertical / Q000662:veterinary*; D007422:Intestines / Q000821:virology; D011247:Pregnancy; D013154:Spleen / Q000821:virology; D034421:Sus scrofa; D013552:Swine; D013553:Swine Diseases / Q000473:pathology* / Q000517:prevention & control / Q000821:virology; D013950:Thymus Gland / Q000821:virology; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage; D017735:Virus Latency
chemical_list: D000914:Antibodies, Viral; D014765:Viral Vaccines
keywords: Latent viral thymus infections; Pig PCV2 chronic infection model; Pig fetuses; Sow vaccination; Viral pool shift in fetal lymph organs