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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| Format: | Article |
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1548038/full |
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| author | Pu Huang Pu Huang Xiaohong Pan Hongli Chen Hongli Chen Mengyue Lei Ying Ma Xiaomei Guo Xiaomei Guo Jiaxin Xie Jixiong Li Jixiong Li Jing Sun Yunzhang Hu Jiandong Shi Jiandong Shi |
| author_facet | Pu Huang Pu Huang Xiaohong Pan Hongli Chen Hongli Chen Mengyue Lei Ying Ma Xiaomei Guo Xiaomei Guo Jiaxin Xie Jixiong Li Jixiong Li Jing Sun Yunzhang Hu Jiandong Shi Jiandong Shi |
| author_sort | Pu Huang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-588d6898b80240a9b51a54d029163fce |
| institution | Matheson Library |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-588d6898b80240a9b51a54d029163fce2025-06-25T05:25:12ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-06-011510.3389/fcimb.2025.15480381548038Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expressionPu Huang0Pu Huang1Xiaohong Pan2Hongli Chen3Hongli Chen4Mengyue Lei5Ying Ma6Xiaomei Guo7Xiaomei Guo8Jiaxin Xie9Jixiong Li10Jixiong Li11Jing Sun12Yunzhang Hu13Jiandong Shi14Jiandong Shi15Yunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaHonghe Health Vocational College, Honghe, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaKunming Medical University, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaKunming Medical University, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaKunming Medical University, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaNational Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaHerpes 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.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1548038/fullHSV-1lytic infectionAhRhost factorantiviral target |
| spellingShingle | Pu Huang Pu Huang Xiaohong Pan Hongli Chen Hongli Chen Mengyue Lei Ying Ma Xiaomei Guo Xiaomei Guo Jiaxin Xie Jixiong Li Jixiong Li Jing Sun Yunzhang Hu Jiandong Shi Jiandong Shi Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression Frontiers in Cellular and Infection Microbiology HSV-1 lytic infection AhR host factor antiviral target |
| title | Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression |
| title_full | Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression |
| title_fullStr | Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression |
| title_full_unstemmed | Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression |
| title_short | Aryl hydrocarbon receptor facilitates HSV-1 lytic infection by enhancing viral gene transcription and receptor expression |
| title_sort | aryl hydrocarbon receptor facilitates hsv 1 lytic infection by enhancing viral gene transcription and receptor expression |
| topic | HSV-1 lytic infection AhR host factor antiviral target |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1548038/full |
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