Pathogenesis of porcine circovirus

Matti Kiupel, Purdue University

Abstract

The first part of this thesis investigated whether PCV2 is the sole pathogen that causes PMWS in pigs and the second part investigated whether PCV2 infects mice and causes a wasting disease in mice. The first part of this thesis failed to confirm PCV2 as the sole pathogen that causes PMWS. Despite success in reproducing PMWS in gnotobiotic and cd/cd pigs, seroconversion of pigs in all study groups to PPV hampered further conclusions on the pathogenesis of PCV2. This thesis confirmed that PCV2 congenitally infects pigs and that PCV2 is necessary for the development of PMWS. The second part of the thesis confirmed that PCV2 replicates in PCV2 inoculated BALB/c mice and causes fetal infection when inoculated into pregnant BALB/c mice, but causes no clinical signs or gross lesions. Microscopic lesions in PCV2 inoculated mice were characterized by expansion of germinal centers in lymphoid organs with large numbers of histiocytic cells and lymphoblasts, apoptosis of histiocytic cells in germinal centers and mild lymphoid depletion of the paracortex. PCV2 nucleic acid was detected in the nuclei and cytoplasm of apoptotic histiocytes in lymphoid tissues as well as in nuclei of hepatocytes in the liver, in nuclei of renal tubular epithelial cells and in the cytoplasm of single lymphocytes in the thymus. In congenitally infected mice, PCV2 nucleic acid was only detected in putative Kupffer cells in livers. PCV2 was associated with apoptosis in spleens, lymph nodes and Peyer's patches of infected BALB/c mice. Upregulation of caspases 1, 2, 3, 6, 7, 8, 11 and 12 and upregulation for the transcripts of apoptosis inhibitors bcl-2, bcl-w and bcl-X and apoptosis promoters' bax, bak and bad was detected in spleens of PCV2-inoculated mice, but not control mice. Apoptosis was further confirmed by light and electron microscopic morphology as well as by positive TUNEL assay and detection of activated caspase 3. The data presented here support the hypothesis that PCV2 induces apoptosis mediated through the activation of caspase 3 in the spleens of infected mice.

Degree

Ph.D.

Advisors

Stevenson, Purdue University.

Subject Area

Veterinary services|Microbiology

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