Foot-and-mouth disease virus (FMDV) causes a highly contagious, debilitating disease in cloven-Further mechanistic studies demonstrated that 3C pro induced proteasome-and caspase-independent protein degradation of karyopherin ␣1 (KPNA1), the nuclear localization signal receptor for tyrosine-phosphorylated STAT1, but not karyopherin ␣2, ␣3, or ␣4. Finally, we showed that the protease activity of 3C pro contributed to the degradation of KPNA1 and thus blocked STAT1/STAT2 nuclear translocation. Taken together, results of our experiments describe for the first time a novel mechanism by which FMDV evolves to inhibit IFN signaling and counteract host innate antiviral responses.
IMPORTANCE
We show that 3Cpro of FMDV antagonizes the JAK-STAT signaling pathway by blocking STAT1/STAT2 nuclear translocation. Furthermore, 3C pro induces KPNA1 degradation, which is independent of proteasome and caspase pathways. The protease activity of 3C pro contributes to the degradation of KPNA1 and governs the ability of 3C pro to inhibit the JAK-STAT signaling pathway. This study uncovers a novel mechanism evolved by FMDV to antagonize host innate immune responses.
Porcine circovirus type 4 (PCV4), a novel circovirus, was first detected in pigs with porcine dermatitis and nephropathy syndrome (PDNS) in China. This study investigated the frequency of porcine circovirus 4 (PCV4) in pigs in Guangxi Province, China, from 2015 to 2019 and its genome diversity. Thirteen of 257 (5.1%) samples were positive for PCV4, 9 of 13 (69.2%) PCV4-positive samples were coinfected with PCV2 or PCV3, and one PCV4-positive sample was coinfected with both PCV2 and PCV3. Similar to other PCVs, PCV4 contains two major ORFs and a stem loop (TTCAGTATTAC). Multiple sequence alignments showed that the PCV4 genome shares 25.3-73.8% nucleotide similarity with other representative circovirus genomes. Interestingly, the PCV4 Cap protein shares relatively high homology (approximately 50%) with the PCV2 Cap protein and has multiple highly homologous peptides. Multiple amino acid sequence alignments of the Cap protein revealed that PCV2 and PCV4 have multiple highly homologous antigen sites and identical receptor binding sites. Therefore, PCV2 and PCV4 may have cross-protective immunogenicity. Phylogenetic analysis showed that PCV4 is closely related to mink circovirus and bat-associated circovirus. In summary, this was the first seroprevalence and genetic investigation of PCV4 in Guangxi Province, China. The results provide insights into the epidemiology and pathogenesis of this important virus.
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