African swine fever virus (ASFV) is a large, double-stranded DNA virus that causes a fatal disease in pigs, posing a threat to the global pig industry. Whereas some ASFV proteins have been found to play important roles in ASFV–host interaction, the functional roles of many proteins are still largely unknown. In this study, we identified I73R , an early viral gene in the replication cycle of ASFV, as a key virulence factor. Our findings demonstrate that pI73R suppresses the host innate immune response by broadly inhibiting the synthesis of host proteins, including antiviral proteins. Crystallization and structural characterization results suggest that pI73R is a nucleic-acid-binding protein containing a Zα domain. It localizes in the nucleus and inhibits host protein synthesis by suppressing the nuclear export of cellular messenger RNA (mRNAs). While pI73R promotes viral replication, the deletion of the gene showed that it is a nonessential gene for virus replication. In vivo safety and immunogenicity evaluation results demonstrate that the deletion mutant ASFV-GZΔ I73R is completely nonpathogenic and provides effective protection to pigs against wild-type ASFV. These results reveal I73R as a virulence-related gene critical for ASFV pathogenesis and suggest that it is a potential target for virus attenuation. Accordingly, the deletion mutant ASFV-GZΔ I73R can be a potent live-attenuated vaccine candidate.

African swine fever virus (ASFV) mainly infects the monocyte/macrophage lineage of pigs and regulates the production of cytokines that influence host immune responses. Several studies have reported changes in cytokine production after infection with ASFV, but the regulatory mechanisms have not yet been elucidated. Therefore, the aim of this study was to examine the immune response mechanism of ASFV using transcriptomic and proteomic analyses. Through multi-omics joint analysis, it was found that ASFV infection regulates the expression of the host NF-B signal pathway and related cytokines. Additionally, changes in the NF-κB signaling pathway and IL-1β and IL-8 expression in porcine alveolar macrophages (PAMs) infected with ASFV were examined. Results show that ASFV infection activates the NF-κB signaling pathway and up-regulates the expression of IL-1β and IL-8. The NF-κB inhibitor BAY11-7082 inhibited the expression profiles of phospho-NF-κB p65, p-IκB, and MyD88 proteins, and inhibited ASFV-induced NF-κB signaling pathway activation. Additionally, the results show that the NF-κB inhibitor BAY11-7082 can inhibit the replication of ASFV and can inhibit IL-1β and, IL-8 expression. Overall, the findings of this study indicate that ASFV infection activates the NF-κB signaling pathway and up-regulates the expression of IL-1β and IL-8, and inhibits the replication of ASFV by inhibiting the NF-κB signaling pathway and interleukin-1 beta and interleukin-8 production. These findings not only provide new insights into the molecular mechanism of the association between the NF-κB signaling pathway and ASFV infection, but also indicate that the NF-κB signaling pathway is a potential immunomodulatory pathway that controls ASF.

Despite a rapid expansion of Porcine reproductive and respiratory syndrome virus (PRRSV) sublineage 8.7 over recent years, very little is known about the patterns of virus evolution, dispersal, and the factors influencing this dispersal. Relying on a national PRRSV surveillance project established over 20 years ago, we expand the available genomic data of sublineage 8.7 from China. We perform independent interlineage and intralineage recombination analyses for the entire study period, which showed a heterogeneous recombination pattern. A series of Bayesian phylogeographic analyses uncover the role of Guangdong as an important infection hub within Asia. The spatial spread of PRRSV is highly linked with a composite of human activities and the heterogeneous provincial distribution of the swine industry, largely propelled by the smaller-scale Chinese rural farming systems in the past years. We sequence all four available modified live vaccines (MLVs) and perform genomic analyses with publicly available data, of which our results suggest a key “leaky” period spanning 2011–2017 with two concurrent amino acid mutations in ORF1a 957 and ORF2 250. Overall, our study provides an in-depth overview of the evolution, transmission dynamics, and potential leaky status of HP-PRRS MLVs, providing critical insights into new MLV development.

In this study, MLVA (multiple-locus variable-number tandem repeat analysis) genotype data ofBrucellastrains from 11 countries along the Silk Road were downloaded from the MLVAbank. MLVA data of strains were applied to the constructed Minimum Spanning Tree to explore the species/biovars distribution, geographic origins, and genetic relationships of the strains analyzed. Moreover, whole-genome sequencing–single-nucleotide polymorphism (WGS-SNP) phylogenetic analysis of the genome ofBrucella melitensisstrains from GenBank was performed to discriminate the relatedness of strains further and investigate the transmission pattern ofB. melitensisbrucellosis. A total of 1,503Brucellastrains were analyzed in this study: 431Brucella abortusstrains (29.8%), 1,009B. melitensisstrains (65.7%), and 63Brucella suisstrains (4.5%).B. melitensisbiovar 3 was the dominant species and was shown to be widespread in all of the examined regions, suggesting that the prevention and surveillance of theB. melitensispopulation are a main challenge in these countries. A wide host spectrum was observed for thisBrucellapopulation; many animal reservoirs are a potential reason for the continuous brucellosis circulation in these countries. Although theB. abortusstrains from the examined regions had common geographic origins, only a few shared genotypes were observed in different countries. These data revealed that the majorityof B. abortusstrains were spreading within the national borders. However, theB. melitensisstrains from Italy originated from a Western Mediterranean lineage; strains from the other 10 countries originated from Eastern Mediterranean lineage, and this lineage was shared by strains from three to nine different countries, suggesting that the introduction and reintroduction of the disease in the 10 countries might have occurred in the past. Furthermore, the most shared MLVA-16 genotypes were formed in theB. melitensisstrains from China, Kazakhstan, and Turkey, suggesting that the introduction and trade in sheep and goats have occurred frequently in these countries. WGS-SNP analysis showed that theB. melitensisin this study originated from the Malta (Italy) region. According to their territorial affiliation between four clade strains from these countries in genotype B, the absence of a clear differentiation suggests that strains continuously expand and spread in countries along with Silk Road. Active exchange and trade of animals (sheep and goats) among these countries are reasonable explanations.B. suisstrains from different nations showed unique geographic origins and epidemiological characteristics. Therefore, there is an urgent need for the control of transfer and trade of infected sheep (goats) in countries along the Silk Road, namely, the strengthening of the entry–exit quarantine of sheep and goats and improvements in the diagnosis of animal brucellosis.