The African swine fever virus I10L protein inhibits the NF- κ B signaling pathway by targeting IKK β

• DOI: 10.1128/jvi.00569-23
• Publication Date: 2023-08-21T13:02:01Z
• Authors: Xing Chen; Lian-Feng Li; Zhong-Yuan Yang; Meilin Li; Shuai Fan; Lan-Fang Shi; Zi-Yu Ren; Xue-Jing Cao; Yuhang Zhang; Shichong Han; Bo Wan; Hua-Ji Qiu; Gaiping Zhang; Wen-Rui He
• Keywords: Proinflammatory cytokine; IκB kinase; IκBα; HEK 293 cells

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is causative agent (ASF), a highly contagious and severe hemorrhagic disease. Efforts prevention treatment ASF have been severely hindered by knowledge gaps viral proteins responsible for modulating host antiviral responses. In this study, we identified I10L protein (pI10L) ASFV as potential inhibitor TNF-α- IL-1β-triggered NF-κB signaling pathway, most canonical part inflammatory The ectopically expressed pI10L remarkably suppressed activation HEK293T PK-15 cells. mutant lacking gene (ASFVΔI10L) induced higher levels proinflammatory cytokines production primary porcine alveolar macrophages (PAMs) compared with its parental HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that inhibits IKKβ phosphorylation reducing K63-linked ubiquitination NEMO, necessary IKKβ. Morever, interacts kinase domain through N-terminus, consequently blocks association substrates IκBα p65, leading to reduced phosphorylation. addition, nuclear translocation efficiency p65 was also altered pI10L. Further biochemical evidence supported amino acids 1-102 on were essential pI10L-mediated suppression pathway. present study clarifies immunosuppressive activity pI10L, provides novel insights into understanding pathobiology development vaccines against ASF. IMPORTANCE caused now widespread many countries affects commercial rearing swine. To date, few safe effective or strategies marketed due large regarding immune evasion mechanisms. deciphered role ASFV-encoded TNF-α-/IL-1β-triggered This thus contributes