Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression

Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression

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 ente...

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Main Authors: Pu Huang, Xiaohong Pan, Hongli Chen, Mengyue Lei, Ying Ma, Xiaomei Guo, Jiaxin Xie, Jixiong Li, Jing Sun, Yunzhang Hu, Jiandong Shi
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
HSV-1
lytic infection
AhR
host factor
antiviral target
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1548038/full
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Summary: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.
ISSN:2235-2988

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