African swine fever virus pB318L, a trans-geranylgeranyl-diphosphate synthase, negatively regulates cGAS-STING and IFNAR-JAK-STAT signaling pathways

PLoS Pathog. 2024 Apr 15;20(4):e1012136. doi: 10.1371/journal.ppat.1012136. eCollection 2024 Apr.

Abstract

African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by the ASF virus (ASFV). ASFV has evolved multiple strategies to escape host antiviral immune responses. Here, we reported that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase, reduced the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs). Mechanically, pB318L not only interacted with STING to reduce the translocation of STING from the endoplasmic reticulum to the Golgi apparatus but also interacted with IFN receptors to reduce the interaction of IFNAR1/TYK2 and IFNAR2/JAK1. Of note, ASFV with interruption of B318L gene (ASFV-intB318L) infected PAMs produces more IFN-I and ISGs than that in PAMs infected with its parental ASFV HLJ/18 at the late stage of infection. Consistently, the pathogenicity of ASFV-intB318L is attenuated in piglets compared with its parental virus. Taken together, our data reveal that B318L gene may partially affect ASFV pathogenicity by reducing the production of IFN-I and ISGs. This study provides a clue to design antiviral agents or live attenuated vaccines to prevent and control ASF.

MeSH terms

  • African Swine Fever Virus*
  • African Swine Fever*
  • Animals
  • Farnesyltranstransferase / metabolism
  • Interferon Type I* / genetics
  • Interferon Type I* / metabolism
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / metabolism
  • Signal Transduction
  • Swine
  • Viral Proteins / metabolism

Substances

  • Farnesyltranstransferase
  • Viral Proteins
  • Nucleotidyltransferases
  • Interferon Type I

Grants and funding

This study was supported by the National Natural Science Foundation of China (grant No. 32322081) (LH), the National Natural Science Foundation of China (grant No. U21A20256) (CW), the National Natural Science Foundation of China (grant No. 32270156) (LH), the National Key Research and Development Program of China (grant No. 2021YFD1801300) (LH), the National Key Research and Development Program of China (grant No. 2021YFD1800100) (CW), the Central Public-interest Scientific Institution Basal Research Fund (grant No. 1610302022013) (LH), and Innovation Program of Chinese Academy of Agricultural Sciences (grant No. CAAS CSLPDCP-2023002) (LH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.