Porcine circovirus type 2 (PCV2) is the primary aetiological agent of porcine circovirusassociated disease in swine. The mechanism of PCV2 pathogenesis remains largely unknown. A newly identified viral protein of PCV2, ORF4, has been suggested to be involved in virus-induced apoptosis. However, there is still no information regarding the molecular mechanism by which ORF4 regulates apoptosis. In this study, we reveal that a physical interaction between the PCV2 ORF4 protein and ferritin heavy chain (FHC) in the cytoplasm of host cells reduced the cellular concentration of FHC. The ORF4-mediated reduction of FHC inhibited reactive oxygen species accumulation in PCV2-infected cells. Consequently, the ORF4 protein inhibited apoptosis in host cells. This may be the first report to describe the mechanism of ORF4 cytoprotection against apoptosis during the early stages of PCV2 infection.

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ObjectiveThe purposes of this study are to explore (1) whether comorbid depressive symptoms in patients with chronic back pain (CBP) affect the pain matrix. And (2) whether the interaction of depression and CBP exacerbates impaired brain function.MethodsThirty-two patients with CBP without comorbid depressive symptoms and thirty patients with CBP with comorbid depressive symptoms were recruited. All subjects underwent functional magnetic resonance imaging (fMRI) scans. The graph theory analysis, mediation analysis, and functional connectivity (FC) analysis were included in this study. All subjects received the detection of clinical depressive symptoms and pain-related manifestations.ResultCompared with the CBP group, subjects in the CBP with comorbid depressive symptoms (CBP-D) group had significantly increased FC in the left medial prefrontal cortex and several parietal cortical regions. The results of the graph theory analyses showed that the area under the curve of small-world property (t = −2.175, p = 0.034), gamma (t = −2.332, p = 0.023), and local efficiency (t = −2.461, p = 0.017) in the CBP-D group were significantly lower. The nodal efficiency in the ventral posterior insula (VPI) (t = −3.581, p = 0.0007), and the network efficiency values (t = −2.758, p = 0.008) in the pain matrix were significantly lower in the CBP-D group. Both the topological properties and the FC values of these brain regions were significantly correlated with self-rating depression scale (SDS) scores (all FDR corrected) but not with pain intensity. Further mediation analyses demonstrated that pain intensity had a mediating effect on the relationship between SDS scores and Pain Disability Index scores. Likewise, the SDS scores mediated the relationship between pain intensity and PDI scores.ConclusionOur study found that comorbid depressive symptoms can aggravate the impairment of pain matrix function of CBP, but this impairment cannot directly lead to the increase of pain intensity, which may be because some brain regions of the pain matrix are the common neural basis of depression and CBP.