IFN-stimulated metabolite transporter ENT3 facilitates viral genome release
Journal
EMBO Reports
Journal Volume
24
Journal Issue
3
Date Issued
2023-03-06
Author(s)
Hsieh, Yu-Ting
Tsai, Tsung-Lin
Huang, Shen-Yan
Heng, Jian-Wen
Huang, Yu-Chia
Tsai, Pei-Yuan
Tu, Chia-Chun
Tsai, Ya-Min
Chang, Pei-Ching
Yu, Guann-Yi
Dzhagalov, Ivan L
Hsu, Chia-Lin
Abstract
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.
Subjects
equilibrative nucleoside transporter; interferon-stimulated gene; macrophage; metabolite transporter; viral replication
SDGs
Publisher
WILEY
Type
journal article