Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages

Wang, Zhao-Yang; Zhen, Zi-Da; Fan, Dong-Ying; Wang, Pei-Gang; An, Jing

doi:10.3390/v12030356

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Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages

¹,

¹,

^1,* and

^1,2,*

Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100093, China

Authors to whom correspondence should be addressed.

Viruses 2020, 12(3), 356; https://doi.org/10.3390/v12030356

Received: 9 February 2020 / Revised: 20 March 2020 / Accepted: 22 March 2020 / Published: 24 March 2020

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Abstract

The Japanese encephalitis virus (JEV) is a Culex mosquito-borne flavivirus and is the pathogenic agent of Japanese encephalitis, which is the most important type of viral encephalitis in the world. Macrophages are a type of pivotal innate immunocyte that serve as sentinels and respond quickly to pathogen invasions. However, some viruses like JEV can hijack macrophages as a refuge for viral replication and immune escape. Despite their crucial involvement in early JEV infection, the transcriptomic landscapes of JEV-infected macrophages are void. Here, by using an in situ JEV infection model, we investigate the transcriptomic alteration of JEV-infected peritoneal macrophages. We found that, upon JEV infection, the macrophages underwent M1 polarization and showed the drastic activation of innate immune and inflammatory pathways. Interestingly, almost all the programmed cell death (PCD) pathways were activated, especially the apoptosis, pyroptosis, and necroptosis pathways, which were verified by the immunofluorescent staining of specific markers. Further transcriptomic analysis and TUNEL staining revealed that JEV infection caused apparent DNA damage. The transcriptomic analysis also revealed that JEV infection promoted ROS and RNS generation and caused oxidative stress, which activated multiple cell death pathways. Our work uncovers the pivotal pathogenic roles of oxidative stress and multiple PCD pathways in JEV infection, providing a novel perspective on JEV–host interactions. View Full-Text

Keywords: Japanese encephalitis virus; transcriptomic analysis; macrophage polarization; programmed cell death; oxidative stress

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MDPI and ACS Style

Wang, Z.-Y.; Zhen, Z.-D.; Fan, D.-Y.; Wang, P.-G.; An, J. Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages. Viruses 2020, 12, 356. https://doi.org/10.3390/v12030356

AMA Style

Wang Z-Y, Zhen Z-D, Fan D-Y, Wang P-G, An J. Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages. Viruses. 2020; 12(3):356. https://doi.org/10.3390/v12030356

Chicago/Turabian Style

Wang, Zhao-Yang, Zi-Da Zhen, Dong-Ying Fan, Pei-Gang Wang, and Jing An. 2020. "Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages" Viruses 12, no. 3: 356. https://doi.org/10.3390/v12030356

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Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages

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