NDV inhibited IFN-β secretion through impeding CHCHD10-mediated mitochondrial fusion to promote viral proliferation

• Published in: Veterinary microbiology 2024-03, Vol.290, p.109973-109973, Article 109973
• Main Authors: Yu, Xibing, Jiang, Hexiang, Li, Jindou, Ding, Jiaxin, Chen, Kainan, Ding, Zhuang, Xu, Xiaohong
• Format: Article
• Language: English
• Subjects: CHCHD10; IFN-β; IRF3; Mitochondrial fusion; NDV; NF-κB
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2023.109973

Newcastle disease virus (NDV) is an RNA virus that can promote its own replication through the inhibition of cellular mitochondrial fusion. The proteins involved in mitochondrial fusion, namely mitofusin 1 (Mfn1) and optic atrophy 1 (OPA1) are associated with interferon-beta (IFN-β) secretion during NDV infection. However, the precise mechanism by which NDV modulates the Mfn1-mediated or OPA1-mediated fusion of mitochondria, thereby impacting IFN-β, remains elusive. This study revealed that the downregulation of the mitochondrial protein known as coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) exerts a negative regulatory effect on OPA1 and Mfn1 in human lung adenocarcinoma (A549) cells during the late stage of NDV infection. This reduction in CHCHD10 expression impeded cellular mitochondrial fusion, subsequently leading to a decline in the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB), ultimately resulting in diminished secretion of IFN-β. In contrast, the overexpression of CHCHD10 alleviated infection-induced detrimental effect in mitochondrial fusion, thereby impeding viral proliferation. In summary, NDV enhances its replication by inhibiting the CHCHD10 protein, which impedes mitochondrial fusion and suppresses IFN-β production through the activation of IRF3 and NF-κB. •NDV infection reduced CHCHD10 expression in A549 cells during the late stages of infection.•Decreased CHCHD10 impeded the mitochondrial fusion process in the late phase of NDV infection.•Decreased CHCHD10 inhibited IFN-β produced by IRF3 and NF-κB activation in the late phase of NDV infection.