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Whole Transcriptome analysis for porcine alveolar macrophage infected by African Swine Fever Virus

ABSTRACT: African swine fever virus (ASFV) is one of the most devastating swine pathogens characterized by nearly 100% mortality in naive herds and was recently emerged the in China. In this study, we generated the expression profile of porcine alveolar macrophages (PAMs) infected with a high pathogenic ASFV (Pig/Heilongjiang/2018 (Pig/HLJ/18) ASFV). Our data indicated that ASFV infection lead to a strong inhibition of host immunity but promote chemokine-mediated signaling pathway and neutrophil chemotaxis. Moreover, ASFV infection can modulate the host miRNA involved regulation network, leading to a significant increase of host metabolism related genes and acceleration of virus replication. Furthermore, ASFV-derived viral small RNAs (vsRNAs) can target some host immune response related genes. In conclusion, our transcriptome-wide data provide some insights into the regulatory mechanism during ASFV infection.

ORGANISM(S): Sus scrofa

PROVIDER: GSE145954 | GEO | 2020/10/20

REPOSITORIES: GEO

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Project description:African swine fever virus (ASFV) is an infectious disease with a mortality rate of nearly 100% in pigs; however, no safe commercial vaccines or antiviral drugs are currently available, which seriously threatens the global pig industry. Therefore, effective biologicals against ASFV are urgently needed. Here, we screened 138 Bacillus subtilis strains, four of which evidently inhibited ASFV replication in vitro. Pigs fed with biologics of different types from the four B. subtilis strains showed reduced pathological changes and viral loads in tissues, with a survival rate of up to 100%. The antiviral activity of B. subtilis was attributed to small-molecule metabolites, rather than to secretory proteins. A total of 169 small molecules were obtained from the metabolites of B. subtilis using LC-MS/MS, arctiin and genistein, which showed the highest inhibition efficiency, suppressing ASFV proliferation at the mid-stage of infection. These molecules acted as competitive inhibitors by complexing the ATP-binding domain of viral topoisomerase II, as demonstrated using molecular docking, biolayer interferometry binding and a competitive decatenation assay, thereby disrupting the catalytic activity of the enzyme and inhibiting ASFV replication. Furthermore, pigs administered arctiin and genistein orally showed decreased mortality and tissue damage. Collectively, these results suggest that the four B. subtilis strains screened may be preventative biologicals against ASFV infection. Our findings pave the way for ASFV prevention and control strategies in the pig industry to curb the economic losses caused by the disease. IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologicals or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.

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Whole Transcriptome analysis for porcine alveolar macrophage infected by African Swine Fever Virus

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