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FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression.

ABSTRACT: Folate receptor alpha (FOLR1) is vital for cells ingesting folate (FA). FA plays an indispensable role in cell proliferation and survival. However, it is not clear whether the axis of FOLR1/FA has a similar function in viral replication. In this study, we used vesicular stomatitis virus (VSV) to investigate the relationship between FOLR1-mediated FA deficiency and viral replication, as well as the underlying mechanisms. We discovered that FOLR1 upregulation led to the deficiency of FA in HeLa cells and mice. Meanwhile, VSV replication was notably suppressed by FOLR1 overexpression, and this antiviral activity was related to FA deficiency. Mechanistically, FA deficiency mainly upregulated apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) expression, which suppressed VSV replication in vitro and in vivo. In addition, methotrexate (MTX), an FA metabolism inhibitor, effectively inhibited VSV replication by enhancing the expression of APOBEC3B in vitro and in vivo. Overall, our present study provided a new perspective for the role of FA metabolism in viral infections and highlights the potential of MTX as a broad-spectrum antiviral agent against RNA viruses.

SUBMITTER: Wu J

PROVIDER: S-EPMC10311271 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression.

Wu Jing J Han Yajing Y Lyu Ruining R Zhang Fang F Jiang Na N Tao Hongji H You Qiao Q Zhang Rui R Yuan Meng M Nawaz Waqas W Chen Deyan D Wu Zhiwei Z

Virologica Sinica 20230405 3

Folate receptor alpha (FOLR1) is vital for cells ingesting folate (FA). FA plays an indispensable role in cell proliferation and survival. However, it is not clear whether the axis of FOLR1/FA has a similar function in viral replication. In this study, we used vesicular stomatitis virus (VSV) to investigate the relationship between FOLR1-mediated FA deficiency and viral replication, as well as the underlying mechanisms. We discovered that FOLR1 upregulation led to the deficiency of FA in HeLa ce ...[more]

PMID: 37028598

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Dataset Information

FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression.

Publications

FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression.

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