pK205R targets the proximal element of IFN-I signaling pathway to assist African swine fever virus to escape host innate immunity at the early stage of infection

• Published in: PLoS pathogens Vol. 20; no. 10; p. e1012613
• Main Authors: Huang, Zhao, Kong, Cuiying, Zhang, WenBo, You, Jianyi, Gao, Chenyang, Yi, Jiangnan, Mai, Zhanzhuo, Chen, Xiongnan, Zhou, Pei, Gong, Lang, Zhang, Guihong, Wang, Heng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.10.2024; Public Library of Science (PLoS)
• Subjects: African swine fever; African Swine Fever - immunology; African Swine Fever - virology; African Swine Fever Virus - immunology; Amino acids; Analysis; Animals; Biological response modifiers; Care and treatment; Diagnosis; Dosage and administration; Gene mutations; Genetic aspects; Health aspects; Hog cholera; Humans; Immune Evasion; Immune response; Immunity, Innate; Interferon; Interferon Type I - immunology; Interferon Type I - metabolism; Pork industry; Receptor, Interferon alpha-beta - genetics; Receptor, Interferon alpha-beta - metabolism; Signal Transduction; Swine; Viral Proteins - genetics; Viral Proteins - metabolism; China; Africa
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012613

African swine fever virus (ASFV) is a nuclear cytoplasmic large DNA virus (NCLDV) that causes devastating hemorrhagic diseases in domestic pigs and wild boars, seriously threatening the development of the global pig industry. IFN-I plays an important role in the body’s antiviral response. Similar to other DNA viruses, ASFV has evolved a variety of immune escape strategies to antagonize IFN-I signaling and maintain its proliferation. In this study, we showed that the ASFV early protein pK205R strongly inhibited interferon-stimulated genes (ISGs) as well as the promoter activity of IFN-stimulated regulatory elements (ISREs). Mechanistically, pK205R interacted with the intracellular domains of IFNAR1 and IFNAR2, thereby inhibiting the interaction of IFNAR1/2 with JAK1 and TYK2 and hindering the phosphorylation and nuclear translocation of STATs. Subsequently, we generated a recombinant strain of the ASFV-pK205R point mutation, ASFV-pK205R 7PM . Notably, we detected higher levels of ISGs in porcine alveolar macrophages (PAMs) than in the parental strain during the early stages of ASFV-pK205R 7PM infection. Moreover, ASFV-pK205R 7PM attenuated the inhibitory effect on IFN-I signaling. In conclusion, we identified a new ASFV immunosuppressive protein that increases our understanding of ASFV immune escape mechanisms.