. doi: 10.1016/j.virs.2026.09.002
Citation: Qiong Mo, Yun-Jia Ning. ACSL3 at the UPR crossroads: Tactician of anti-influenza defense, target of influenza offense .VIROLOGICA SINICA, 2026, 41(5) : 1265-1267.  http://dx.doi.org/10.1016/j.virs.2026.09.002

ACSL3立于未折叠蛋白反应十字路口:抗流感防御之谋士,流感进攻之靶心

  • 通讯作者: 宁云佳, nyj@wh.iov.cn
  • 收稿日期: 2026-07-02
    录用日期: 2026-08-31
  • 病毒与宿主之间无休止的军备竞赛塑造了双方精巧的分子策略。宿主限制因子是抵御入侵病原体、减弱其致病性的前线防御者;而病毒则进化出多种机制来中和或破坏这些屏障。甲型流感病毒(IAV)仍是持续存在的全球健康负担,但许多限制因子及其病毒应对机制仍不清楚,制约了以宿主为靶点的新型治疗策略的开发。在Virologica Sinica近期发表的一篇研究文章中,Zhao等鉴定长链脂酰辅酶A合成酶家族成员3(ACSL3)为一种新型广谱抗IAV宿主限制因子。该工作不仅扩大了IAV限制因子的谱系,还揭示了ACSL3在未折叠蛋白反应(UPR)信号通路十字路口处协调抗病毒状态的全新角色,以及IAV靶向降解ACSL3的反制策略,从而为理解内质网(ER)界面的病毒-宿主相互作用提供了新的概念框架。本文在深入评析该研究创新性与科学价值的基础上,亦探讨了当前研究的局限性,并提出若干亟待解决的关键科学问题,如ACSL3与UPR感受器相互作用的分子细节、IAV诱导ACSL3降解的具体机制以及抗病毒UPR的下游效应通路等。解答这些关键问题,将加深我们对ACSL3-IAV相互作用乃至更广泛病毒-宿主互作的认知,并为宿主靶向的抗病毒创新策略研发提供重要启示。

ACSL3 at the UPR crossroads: Tactician of anti-influenza defense, target of influenza offense

  • Corresponding author: Yun-Jia Ning, nyj@wh.iov.cn
  • Received Date: 02 July 2026
    Accepted Date: 31 August 2026
  • Highlights
    1 A new dimension of the host-IAV arms race is revealed, centered on ACSL3 at the UPR crossroads.
    2 Key questions remain regarding ACSL3-UPR sensor interfaces and ACSL3 induction/degradation mechanisms.
    3 Addressing the questions will advance ACSL3-IAV interplay insights and may inform host-targeted therapy.

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    7. Liu, L.L., Yin, Y.Q., Ma, K.X., Xing, J.C., Ren, X.X., Huang, J.Y., Liao, M., Qi, W.B., Huang, L.H., 2024. Identification critical host factors for Japanese encephalitis virus replication via CRISPR screening of human sgRNA library. Vet Microbiol, 293, 110099.

    8. Martin-Sancho, L., Tripathi, S., Rodriguez-Frandsen, A., Pache, L., Sanchez-Aparicio, M., Mcgregor, M.J., Haas, K.M., Swaney, D.L., Nguyen, T.T., Mamede, J.I., et al., 2021. Restriction factor compendium for influenza A virus reveals a mechanism for evasion of autophagy. Nat Microbiol, 6, 1319-1333.

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    10. Poppelreuther, M., Rudolph, B., Du, C., Grossmann, R., Becker, M., Thiele, C., Ehehalt, R., Fullekrug, J., 2012. The N-terminal region of acyl-CoA synthetase 3 is essential for both the localization on lipid droplets and the function in fatty acid uptake. J Lipid Res, 53, 888-900.

    11. Sae-Fung, A., Vinayavekhin, N., Fadeel, B., Jitkaew, S., 2024. ACSL3 is an unfavorable prognostic marker in cholangiocarcinoma patients and confers ferroptosis resistance in cholangiocarcinoma cells. NPJ Precis Oncol, 8, 284.

    12. Yao, H., Ye, J., 2008. Long Chain Acyl-CoA Synthetase 3-mediated Phosphatidylcholine Synthesis Is Required for Assembly of Very Low Density Lipoproteins in Human Hepatoma Huh7 Cells *. Journal of Biological Chemistry, 283, 849-854.

    13. Zhang, B., Han, L., Cui, C., Huang, J., Zhu, Q., Lei, C., Xu, S., 2026. Influenza a virus NS2 suppresses NFKB/NF-κB signaling to facilitate viral replication by mediating the autophagic-degradation of IKBKG/NEMO. Autophagy, 10.1080/15548627.2026.2676801.

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    ACSL3 at the UPR crossroads: Tactician of anti-influenza defense, target of influenza offense

      Corresponding author: Yun-Jia Ning, nyj@wh.iov.cn
    • a. Department of Infectious Diseases, The Affiliated People's Hospital of Ningbo University, Ningbo 315020, China;
    • b. State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
    • c. University of Chinese Academy of Sciences, Beijing 101408, China;
    • d. Hubei Jiangxia Laboratory, Wuhan 430200, China

    Abstract: Highlights
    1 A new dimension of the host-IAV arms race is revealed, centered on ACSL3 at the UPR crossroads.
    2 Key questions remain regarding ACSL3-UPR sensor interfaces and ACSL3 induction/degradation mechanisms.
    3 Addressing the questions will advance ACSL3-IAV interplay insights and may inform host-targeted therapy.

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