RT Journal Article
SR Electronic
T1 Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.29.014209
DO 10.1101/2020.03.29.014209
A1 Danielle E Anderson
A1 Jin Cui
A1 Qian Ye
A1 Baoying Huang
A1 Wenhong Zu
A1 Jing Gong
A1 Weiqiang Liu
A1 So Young Kim
A1 Biao Guo Yan
A1 Kristmundur Sigmundsson
A1 Xiao Fang Lim
A1 Fei Ye
A1 Peihua Niu
A1 Xuming Zhou
A1 Wenjie Tan
A1 Lin-Fa Wang
A1 Xu Tan
YR 2020
UL http://biorxiv.org/content/early/2020/03/30/2020.03.29.014209.abstract
AB Bats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the tolerance of viral infections in bats. Here we report the establishment and screening of genome-wide RNAi library and CRISPR library for the model megabat, Pteropus Alecto. We used the complementary RNAi and CRISPR libraries to interrogate Pteropus Alecto cells for infection with two different viruses, mumps virus and Influenza A virus, respectively. Screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C-1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells as well as in human cells. MTHFD1 inhibitor carolacton potently blocked replication of several RNA viruses including SARS-CoV-2. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad spectrum antiviral therapy.