2. Academic Validation
  3. NSP1 of Alongshan virus antagonizes type I interferon responses by promoting STUB1-mediated degradation of RIG-I

NSP1 of Alongshan virus antagonizes type I interferon responses by promoting STUB1-mediated degradation of RIG-I

  • Cell Commun Signal. 2026 Mar 24;24(1):262. doi: 10.1186/s12964-026-02833-z.
Fengchao Xu 1 2 3,  Hongxiao Song 1 2 3,  Rongxing Ming 4,  Yujia Zhu 1 2 3,  Mian Huang 1 2 3,  Jing Xu 5,  Le Wang 1,  Xiaolu Li 6,  Fan Yang 7,  Huifan Ji 1,  Guangyun Tan 8 9 10
Affiliations

Affiliations

  • 1 Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
  • 2 Jilin Provincial Key Laboratory of Metabolic Liver Diseases, Jilin University, Changchun, Jilin, 130021, China.
  • 3 China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, Changchun, Jilin, 130021, China.
  • 4 Department of Respiratory Medicine, The First People's Hospital of Nankang District, Ganzhou, Jiangxi, 341400, China.
  • 5 Health Examination Center, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
  • 6 Department of Pediatrics, the First Hospital, Jilin University, Changchun, Jilin, 130021, China.
  • 7 Department of Anesthesiology, the First Hospital, Jilin University, Changchun, Jilin, 130021, China.
  • 8 Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, 130021, China. [email protected].
  • 9 Jilin Provincial Key Laboratory of Metabolic Liver Diseases, Jilin University, Changchun, Jilin, 130021, China. [email protected].
  • 10 China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, Changchun, Jilin, 130021, China. [email protected].
PMID: 41877189 DOI: 10.1186/s12964-026-02833-z
Abstract

Emerging tick-borne viruses have become a significant public health concern due to their association with severe human illnesses. Among these, Alongshan virus (ALSV), a segmented RNA virus first identified in northeastern China, has been linked to febrile illness, presenting with fever, headache, myalgia, and, in severe cases, multi-organ failure. Despite its clinical relevance, the mechanisms by which ALSV evades host immune defenses remain poorly understood. Here, we identify NSP1, a nonstructural protein of ALSV, as a potent inhibitor of type I interferon (IFN-I) production, specifically targeting the RIG-I signaling pathway. Mechanistically, NSP1 binds to RIG-I, preventing its interaction with MAVS and facilitating RIG-I’s STUB1-mediated K48-linked polyubiquitination and subsequent proteasomal degradation. By disrupting the RIG-I/MAVS complex and promoting the targeted degradation of RIG-I, NSP1 effectively suppresses the IFN-I response, a critical component of the host Antiviral defense. Our study provides a dual mechanism through which NSP1 impairs immune detection, highlighting its role in immune evasion and viral persistence. These findings not only advance our understanding of ALSV pathogenesis but also offer a potential therapeutic target for Antiviral interventions, shedding light on broader strategies employed by viruses to subvert host immune responses.

Keywords

ALSV; Interferon; MAVS; NSP1; RIG-I.

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