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

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

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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.

Folate receptor alpha(FOLR1)Folate receptorVesicular stomatitis virus(VSV)Apolipoprotein B mRNA editing enzymecatalytic subunit 3(APOBEC3)Methotrexate(MTX)

Jing Wu、Yajing Han、Ruining Lyu、Fang Zhang、Na Jiang、Hongji Tao、Qiao You、Rui Zhang、Meng Yuan、Waqas Nawaz、Deyan Chen、Zhiwei Wu

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Center for Public Health Research,Medical School of Nanjing University,Nanjing,210093,China

Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment,South China Institute of Environmental Sciences,Ministry of Ecology and Environment,Guangzhou,510535,China

Department of Bum and Plastic Surgery,Affiliated Hospital of Zunyi Medical University,Zunyi,563099,China

H(o)pital Maisonneuve-Rosemont,School of Medicine,University of Montreal,Quebec,999040,Canada

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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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaMajor Research and Development ProjectNanjing University-Ningxia University Collaborative Project

31970149819008232018ZX103014062017BN04

2023

10.1016/j.virs.2023.04.001

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
年,卷(期)：2023.38(3)
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