Porcine Circovirus type 2 (PCV2) causes apoptosis in experimentally inoculated BALB/c mice

PCV2 replicated and was associated with apoptosis in spleens, lymph nodes and Peyer's patches of infected BALB/c mice. Upregulation of caspase 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 sPCV and mPCV 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. PCV2 nucleic acid was detected by in-situ hybridization in the nuclei and cytoplasm of such apoptotic cells.The data presented here support the hypothesis that PCV2 induces apoptosis mediated through the activation of caspases 8 and 3 in the spleens of infected mice.Circoviruses, the smallest animal DNA viruses known so far, have a single copy of circular single-stranded ambisense DNA genome that varies in size between 1.7 and 2.3 kb. Animal circoviruses have been demonstrated in chickens (chicken anemia virus, ChAV, [49]), pigs (porcine circovirus, PCV, [45]), pigeons (pigeon circovirus, [47]) and psittacines (psittacine beak and feather disease virus, PBFDV, [36]). Porcine circovirus (PCV), an approximately 17 nm in diameter, non-enveloped virus with icosahedral symmetry, was originally identified as a noncytopathic contaminant of the PK-15 porcine kidney cell line [44]. The genome of PK-15 derived virus has been sequenced [28] and isolates of PCV that are genetically like PK-15 cell PCV are referred to as PCV1 [29]. Inoculation studies in pigs using PK-15 derived PCV1 did not result in clinical disease [1,46]. In 1990's, field strains of PCV have been found in lesions of pigs with postweaning multisystemic wasting syndrome (PMWS) [2,5,6,10,17,31,33,42]. Isolates of PMWS-associated PCV are genetically and antigenically different from the PK-15 cell PCV and are referred to as PCV2 [29].PMWS is clinically characterized by progressive weight loss, dyspnea, tach