Targeting Aryl Hydrocarbon Receptor Signaling Enhances Type I Interferon-Independent Resistance to Herpes Simplex Virus

Jincheng Chen; Juan Liang; Hui Xu; Wenqi Liu; Shuyan Liu; Lian Duan; Fang Li; Zhaoqin Wang; Yingxia Liu; Brian McSharry; Carl G. Feng; Guoliang Zhang

doi:10.1128/Spectrum.00473-21

Microbiology Spectrum (Oct 2021)

Targeting Aryl Hydrocarbon Receptor Signaling Enhances Type I Interferon-Independent Resistance to Herpes Simplex Virus

Jincheng Chen,
Juan Liang,
Hui Xu,
Wenqi Liu,
Shuyan Liu,
Lian Duan,
Fang Li,
Zhaoqin Wang,
Yingxia Liu,
Brian McSharry,
Carl G. Feng,
Guoliang Zhang

Affiliations

Jincheng Chen: Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China
Juan Liang: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
Hui Xu: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
Wenqi Liu: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
Shuyan Liu: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
Lian Duan: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
Fang Li: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
Zhaoqin Wang: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
Yingxia Liu: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China
Brian McSharry: Infections, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
Carl G. Feng: Infections, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
Guoliang Zhang: National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China

DOI: https://doi.org/10.1128/Spectrum.00473-21
Journal volume & issue: Vol. 9, no. 2

Abstract

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ABSTRACT The aryl hydrocarbon receptor (AHR) is a ligand-activated transcript factor that plays an important role in regulating immunity and cell differentiation. However, its role in cell-autonomous antiviral resistance has not been fully elucidated. Here, we show that interruption of AHR signaling in human cells by a chemical antagonist or genetic targeting led to significant reductions in the replication of herpes simplex virus 1 (HSV-1) and cytomegalovirus (CMV), revealing an unexpected proviral function of AHR. Interestingly, the enhanced viral control in the absence of AHR is independent of type I interferon (IFN) signaling. Together, these results reveal a previously unknown function of AHR in promoting viral replication in vitro and suggest a potential intervention point for treating viral disease. IMPORTANCE This study describes how a virus might utilize host aryl hydrocarbon receptor signaling to promote its replication, even in the presence of type I interferons.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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