IFN-stimulated metabolite transporter ENT3 facilitates viral genome release

Yu Ting Hsieh, Tsung Lin Tsai, Shen Yan Huang, Jian Wen Heng, Yu Chia Huang, Pei Yuan Tsai, Chia Chun Tu, Tai Ling Chao, Ya Min Tsai, Pei Ching Chang, Chien Kuo Lee, Guann Yi Yu, Sui Yuan Chang, Ivan L. Dzhagalov, Chia Lin Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


An increasing amount of evidence emphasizes the role of metabolic reprogramming in immune cells to fight infections. However, little is known about the regulation of metabolite transporters that facilitate and support metabolic demands. In this study, we found that the expression of equilibrative nucleoside transporter 3 (ENT3, encoded by solute carrier family 29 member 3, Slc29a3) is part of the innate immune response, which is rapidly upregulated upon pathogen invasion. The transcription of Slc29a3 is directly regulated by type I interferon-induced signaling, demonstrating that this metabolite transporter is an interferon-stimulated gene (ISG). Suprisingly, we unveil that several viruses, including SARS-CoV-2, require ENT3 to facilitate their entry into the cytoplasm. The removal or suppression of Slc29a3 expression is sufficient to significantly decrease viral replication in vitro and in vivo. Our study reveals that ENT3 is a pro-viral ISG co-opted by some viruses to gain a survival advantage.

Original languageEnglish
JournalEMBO Reports
StateAccepted/In press - 2023


  • equilibrative nucleoside transporter
  • interferon-stimulated gene
  • macrophage
  • metabolite transporter
  • viral replication


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