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Equilibrative Nucleoside Transporter 3 is an IFN-stimulated Gene that Facilitates Viral Genome Release

View ORCID ProfileYu-Ting Hsieh, View ORCID ProfileTsung-Lin Tsai, View ORCID ProfileChia-Chun Tu, Shen-Yan Huang, Jian-Wen Heng, Pei-Yuan Tsai, Tai-Ling Chao, View ORCID ProfileYa-Min Tsai, Pei-Ching Chang, View ORCID ProfileChien-Kuo Lee, View ORCID ProfileGuann-Yi Yu, View ORCID ProfileSui-Yuan Chang, View ORCID ProfileIvan L. Dzhagalov, View ORCID ProfileChia-Lin Hsu
doi: https://doi.org/10.1101/2022.04.27.489746
Yu-Ting Hsieh
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Tsung-Lin Tsai
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
7Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan
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Chia-Chun Tu
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Shen-Yan Huang
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Jian-Wen Heng
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Pei-Yuan Tsai
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Tai-Ling Chao
2Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
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Ya-Min Tsai
3Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan
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  • ORCID record for Ya-Min Tsai
Pei-Ching Chang
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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Chien-Kuo Lee
4Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei 100, Taiwan
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Guann-Yi Yu
5National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan
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Sui-Yuan Chang
3Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100, Taiwan
6Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan
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Ivan L. Dzhagalov
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
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  • ORCID record for Ivan L. Dzhagalov
Chia-Lin Hsu
1Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
7Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan
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  • For correspondence: clhsu@nycu.edu.tw Chialin.hsu@ym.edu.tw
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Abstract

An increasing body of evidence emphasizes the role of metabolic reprogramming in immune cells to fight off infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that equilibrative nucleoside transporter 3 (ENT3) expression is part of the innate immune response, and is rapidly upregulated upon bacterial and viral infection. The transcription of ENT3 is directly under the regulation of IFN-induced signaling, positioning this metabolite transporter as an Interferon-stimulated gene (ISG). Moreover, we unveil that several viruses, including SARS-CoV2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of ENT3 expression is sufficient to significantly decrease viral replication in vitro and in vivo.

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Posted April 28, 2022.
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Equilibrative Nucleoside Transporter 3 is an IFN-stimulated Gene that Facilitates Viral Genome Release
Yu-Ting Hsieh, Tsung-Lin Tsai, Chia-Chun Tu, Shen-Yan Huang, Jian-Wen Heng, Pei-Yuan Tsai, Tai-Ling Chao, Ya-Min Tsai, Pei-Ching Chang, Chien-Kuo Lee, Guann-Yi Yu, Sui-Yuan Chang, Ivan L. Dzhagalov, Chia-Lin Hsu
bioRxiv 2022.04.27.489746; doi: https://doi.org/10.1101/2022.04.27.489746
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Equilibrative Nucleoside Transporter 3 is an IFN-stimulated Gene that Facilitates Viral Genome Release
Yu-Ting Hsieh, Tsung-Lin Tsai, Chia-Chun Tu, Shen-Yan Huang, Jian-Wen Heng, Pei-Yuan Tsai, Tai-Ling Chao, Ya-Min Tsai, Pei-Ching Chang, Chien-Kuo Lee, Guann-Yi Yu, Sui-Yuan Chang, Ivan L. Dzhagalov, Chia-Lin Hsu
bioRxiv 2022.04.27.489746; doi: https://doi.org/10.1101/2022.04.27.489746

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