ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1548038
This article is part of the Research TopicPerspectives in Virus and Host: 2025View all 7 articles
Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression
Provisionally accepted
Jiandong Shi*
Pu HuangHongli ChenMengyue Lei
Ma YingXiaohong PanXiaomei GuoJiaxin XieJixiong Li
Jing SunYunzhang Hu- Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan Province, China
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Herpes simplex virus type 1 (HSV-1) is a major human pathogen with significant morbidity in neonates and immunocompromised individuals. However, antiviral drugs targeting HSV-1 are emerging with antiviral resistance, highlighting the need to identify new targets for future treatment. Once HSV-1 enters the host cells, it recruits host factors to facilitate viral life cycle.In this study, we showed that aryl hydrocarbon receptor (AhR), a ligand-activated nuclear receptor, is required for HSV-1 effective replication and offers an opportunity for pharmacological intervention. Our results showed that HSV-1 infection activates AhR signaling in an interferon-dependent manner. Pharmacological inhibition or knockout of AhR reduced the expression of viral proteins and infectious progeny, while increased AhR signaling promoted the expression of viral proteins and viral replication. Mechanistically, AhR formed a transcription complex with cyclin T1, VP16 and RNA Pol II in the nucleus, bound to viral gene promoters, and promoted their transcription. Additionally, AhR promoted viral replication partially by facilitating the expression of multiple viral receptors. Collectively, AhR is a proviral host factor for HSV-1, and thus may be used as a promising host-directed antiviral target.
Keywords: HSV-1, Lytic infection, AhR, host factor, Antiviral target
Received: 19 Dec 2024; Accepted: 10 Jun 2025.
Copyright: © 2025 Shi, Huang, Chen, Lei, Ying, Pan, Guo, Xie, Li, Sun and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jiandong Shi, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650031, Yunnan Province, China
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