Two orthobunyaviruses: OYAV and EBIV co-opt the AhR-CYP1A1 axis to suppress type I interferon responses

Qianyun Hu; Fei Wang; Xiaoyu Wang; Xiaokui Li; Zhiming Yuan; Maohua Zhong; Han Xia

doi:10.1016/j.virs.2026.04.001

April 2026

. doi: 10.1016/j.virs.2026.04.001

Citation: Qianyun Hu, Fei Wang, Xiaoyu Wang, Xiaokui Li, Zhiming Yuan, Maohua Zhong, Han Xia. Two orthobunyaviruses: OYAV and EBIV co-opt the AhR-CYP1A1 axis to suppress type I interferon responses .VIROLOGICA SINICA, 2026, 41(2) : 329-342. http://dx.doi.org/10.1016/j.virs.2026.04.001

两种正布尼亚病毒：OYAV与EBIV利用AhR-CYP1A1轴抑制I型干扰素反应

胡倩云 ^a,b ,
王飞 ^a ,
王小钰 ^a,b ,
李晓葵 ^a,b ,
袁志明 ^a,b,, ,
钟茂华 ^c,, ,
夏菡 ^a,c,d,,

a 中国科学院武汉病毒研究所病毒与生物安全重点实验室, 湖北武汉;
b 中国科学院大学, 北京;
c 武汉科技大学医学院感染、免疫与肿瘤微环境研究所, 职业危害识别与控制湖北省重点实验室, 湖北武汉;
d 湖北江夏实验室, 湖北武汉

通讯作者： 袁志明, yzm@wh.iov.cn; 钟茂华, zmh@wust.edu.cn; 夏菡, hanxia@wh.iov.cn
收稿日期： 2025-08-28
录用日期： 2026-04-02

摘要

I型干扰素（IFN-I）系统是抵御病毒感染的第一道防线，而正布尼亚病毒如何抑制这一通路尚不明确。本研究鉴定出细胞色素P450 1A1（CYP1A1）是促进两种新发正布尼亚病毒——Oya病毒(OYAV)与艾比湖病毒（EBIV）感染的关键宿主因子。转录组学与功能分析表明，CYP1A1过表达能增强病毒RNA合成，而通过CRISPR-Cas9技术敲除该基因则会抑制病毒感染。机制研究表明，OYAV与EBIV可激活芳烃受体（AhR），驱动其核转位并随后上调CYP1A1的表达。CYP1A1缺失会增强IFN-β产生及干扰素刺激基因（ISG）表达，而过表达该基因则抑制抗病毒信号通路，进一步揭示其经典代谢功能之外的免疫调节作用。本研究系统阐明了AhR-CYP1A1轴作为新发正布尼亚病毒共同利用的免疫逃逸策略，并提示该天然免疫通路可作为应对这类新发病毒威胁的潜在治疗靶点。
- EB病毒(EBV)
- , EB病毒核抗原1(EBNA1)
- , DEAD框解旋酶5(DDX5)
- , FL118
- , 裂解复制

Two orthobunyaviruses: OYAV and EBIV co-opt the AhR-CYP1A1 axis to suppress type I interferon responses

Qianyun Hu ^a,b ,
Fei Wang ^a ,
Xiaoyu Wang ^a,b ,
Xiaokui Li ^a,b ,
Zhiming Yuan ^a,b,, ,
Maohua Zhong ^c,, ,
Han Xia ^a,c,d,,

a. Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China;
b. University of Chinese Academy of Sciences, Beijing 100049, China;
c. Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, Wuhan 430065, China;
d. Hubei Jiangxia Laboratory, Wuhan 430200, China

Corresponding author: Zhiming Yuan, yzm@wh.iov.cn Maohua Zhong, zmh@wust.edu.cn Han Xia, hanxia@wh.iov.cn
Received Date: 28 August 2025
Accepted Date: 02 April 2026

Abstract

The type I interferon (IFN-I) system serves as a frontline defense against viral infection, yet how orthobunyaviruses counteract this pathway remains poorly defined. Here, we identify cytochrome P450 1A1 (CYP1A1) as a crucial host factor promoting infection by two emerging orthobunyaviruses—Oya virus (OYAV) and Ebinur Lake virus (EBIV). Transcriptomic and functional analyses demonstrate that CYP1A1 overexpression enhances viral RNA synthesis, whereas its CRISPR-Cas9-mediated knockout attenuates infection. Mechanistically, OYAV and EBIV activate the aryl hydrocarbon receptor (AhR), driving its nuclear translocation and subsequent upregulation of CYP1A1. Deficiency of CYP1A1 potentiates IFN-β production and interferon-stimulated gene (ISG) expression, while its overexpression suppressed antiviral signaling, revealing an immunomodulatory role that is distinct from its canonical metabolic function. Collectively, this work defines the AhR-CYP1A1 axis as a conserved immune-evasion module exploited by emerging orthobunyaviruses and highlights the innate immune pathway as a potential therapeutic target against these emerging threats.
- Orthobunyavirus
- , Cytochrome P450 1A1 (CYP1A1)
- , Type I interferon (IFN-I)
- , Aryl hydrocarbon receptor (AhR)
- , Immune evasion

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