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Summary Emerging porcine pestivirus diseases frequently challenge prevention and control strategies in the swine industry. Over the past decade, a few novel pestiviruses have been identified in pigs. This article focuses on the recently emerging atypical porcine pestivirus (APPV) that potentially threatens global swine herd health security. The virus was first identified in 2016, in the United States and thereafter, accumulated evidence shows that it is currently distributed in three continents. The clinical presentation of APPV‐infected pigs is characterized by congenital tremor (CT) type A‐II in piglets, while adult pigs may become persistent carriers and shedders. Here, a literature review is conducted to summarize the published findings in the virus genomic biology, transmission, epidemiology, pathogenesis, and diagnosis, which would shed light on acceleration of development of anti‐APPV strategies.

Porcine circovirus type 3 (PCV3) contains two major open reading frames (ORFs) and the ORF2 gene encodes the major structural capsid protein. In this study, nuclear localization of ORF2 was demonstrated by fluorescence observation and subcellular fractionation assays in ORF2-transfected PK-15 cells. The subcellular localization of truncated ORF2 indicated that the 38 N-terminal amino acids were responsible for the nuclear localization of ORF2. The truncated and site-directed mutagenesis of this domain were constructed, and the results demonstrated that the basic amino acid residues at positions 8-32 were essential for the strict nuclear localization. The basic motifs 8 RRR-R-RRR 16 and 16 RRRHRRR 22 were further shown to be the key functional nucleolar localization signals that guide PCV3 ORF2 into nucleoli. Furthermore, sequence analysis showed that the amino acids of PCV3 nuclear localization signals were highly conserved. Overall, this study provides insight into the biological and functional characteristics of the PCV3 ORF2 protein.case of PCVs, the N-terminus of ORF2 is rich in basic amino acids and displays nuclear localization signals (NLSs) [14][15][16]. The NLS is a short stretch of amino acids that mediates the transport of nuclear proteins into the nucleus. NLS motifs play a key role in this mechanism. NLS sequences are often composed of basic amino acids and can be classified as either monopartite or bipartite motifs [17,18]. The nuclear targeting of PCV2 ORF2 is directed by the bipartite motifs situated at the N-terminus of the proteins [14,15]. NLSs of PCV1 ORF2 show high homologies to classical monopartite or bipartite NLS, which is essential for the complete nuclear import of PCV1 ORF2. The N-terminus of PCV1 and PCV2 ORF2 contain several conserved basic amino acid stretches [15,19], and shares 70.7% in nucleotide identity and 82.9% in amino acid similarity.Verification of NLS and demonstration of intracellular distribution facilitate understanding of viral protein function. The amino acids of PCV3 ORF2 are markedly different from those of the other PCVs. This led us to study the functional motifs in nuclear targeting of PCV3 ORF2. In this study, a series of recombinant plasmids expressing PCV3 ORF2 fused to EGFP were constructed, and we identified the main motifs of the NLSs mediating nuclear localization of PCV3 ORF2.

Atypical porcine pestivirus (APPV) has been identified as the main causative agent for congenital tremor (CT) type A-II in piglets, which is threatening the health of the global swine herd. However, the evolution of APPV remains largely unknown. In this study, phylogenetic analysis showed that APPV could be divided into three phylogroups (I, II, and III). Phylogroups I and II included viral strains from China, while phylogroup III contained strains from Europe, North America, and Asia. Phylogroups I and II are tentatively thought to be of Chinese origin. Next, compositional property analysis revealed that a high frequency of nucleotide A and A-end codons was used in the APPV genome. Intriguingly, the analysis of preferred codons revealed that the AGA[Arg] and AGG[Arg] were overrepresented. Dinucleotide CC was found to be overrepresented, and dinucleotide CG was underrepresented. Furthermore, it was found that the weak codon usage bias of APPV was mainly dominated by selection pressures versus mutational forces. The codon adaptation index (CAI), relative codon deoptimization index (RCDI), and similarity index (SiD) analyses showed that the codon usage patterns of phylogroup II and III were more similar to the one of a pig than phylogroup I, suggesting that phylogroup II and III may be more adaptive to pigs. Overall, this study provides insights into APPV evolution through phylogeny and codon usage pattern analysis.

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Atypical porcine pestivirus (APPV) is an emerging porcine virus that threatens global swine production. Pestiviruses can prevent interferon (IFN) production to avoid the host innate immune response, and the N pro viral protein can play a critical role. Knowledge of the host immune response to APPV infection is limited. Here, we showed that the IFN-β production was suppressed by APPV-N pro and the IFN regulatory factor 3 (IRF3) promoter activity stimulated by adaptor molecules of the IFN-β signaling pathway was also inhibited in the APPV-N pro -expressed cells. The APPV-N pro was able to interact with IRF3 and interfere the phosphorylation of IRF3, indicated that the IFN-β antagonism of APPV-N pro mainly depended on blocking IRF3 activity. To identify the functional region of APPV-N pro , a panel of truncated APPV-N pro was constructed, and its influence on the IRF3 activation was investigated. The results showed that the N-terminal 31-51 amino acids of APPV-N pro were mainly associated with inhibition of the IFN-β response. Taken together, this is the first study focusing on elucidating the function of APPV protein by revealing a novel mechanism of N pro in disruption of host IFN-β production, which will enlighten future study in addressing APPV pathogenesis and immune evasion.