中国病毒学2023，Vol.38Issue(3) ：409-418.DOI:10.1016/j.virs.2023.04.001

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

Jing Wu Yajing Han Ruining Lyu Fang Zhang Na Jiang Hongji Tao Qiao You Rui Zhang Meng Yuan Waqas Nawaz Deyan Chen Zhiwei Wu
中国病毒学2023，Vol.38Issue(3) ：409-418.DOI:10.1016/j.virs.2023.04.001
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FOLR1-induced folate deficiency reduces viral replication via modulating APOBEC3 family expression

Jing Wu 1Yajing Han 2Ruining Lyu 1Fang Zhang 3Na Jiang 1Hongji Tao 1Qiao You 1Rui Zhang 1Meng Yuan 1Waqas Nawaz 4Deyan Chen 1Zhiwei Wu5
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作者信息

  • 1. Center for Public Health Research,Medical School of Nanjing University,Nanjing,210093,China
  • 2. Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment,South China Institute of Environmental Sciences,Ministry of Ecology and Environment,Guangzhou,510535,China
  • 3. Department of Bum and Plastic Surgery,Affiliated Hospital of Zunyi Medical University,Zunyi,563099,China
  • 4. H(o)pital Maisonneuve-Rosemont,School of Medicine,University of Montreal,Quebec,999040,Canada
  • 5. Center for Public Health Research,Medical School of Nanjing University,Nanjing,210093,China;Medical School and Jiangsu Key Laboratory of Molecular Medicine,Nanjing University,Nanjing,210093,China;State Key Lab of Analytical Chemistry for Life Science,Nanjing University,Nanjing,210093,China
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Abstract

Folate receptor alpha(FOLR1)is vital for cells ingesting folate(FA).FA plays an indispensable role in cell pro-liferation 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 sup-pressed 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.

Key words

Folate receptor alpha(FOLR1)/Folate receptor/Vesicular stomatitis virus(VSV)/Apolipoprotein B mRNA editing enzyme/catalytic subunit 3(APOBEC3)/Methotrexate(MTX)

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基金项目

National Natural Science Foundation of China(31970149)

National Natural Science Foundation of China(81900823)

Major Research and Development Project(2018ZX10301406)

Nanjing University-Ningxia University Collaborative Project(2017BN04)

出版年

2023
中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子：0.393
ISSN：1674-0769
参考文献量54
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