Identification critical host factors for Japanese encephalitis virus replication via CRISPR screening of human sgRNA library.

Vet Microbiol

State Key Laboratory for Animal Disease Control and Prevention, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture and Rural Affairs, Guangzhou 510642, China; National and Regional Joint Engineering Laboratory for Medicament of Zoono

Published: June 2024


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Article Abstract

Japanese encephalitis virus (JEV) is a pathogen with a substantial impact on both livestock and human health. However, the critical host factors in the virus life cycle remain poorly understood. Using a library comprising 123411 small guide RNAs (sgRNAs) targeting 19050 human genes, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based screen to identify essential genes for JEV replication. By employing knockout or knockdown techniques on genes, we identified eleven human genes crucial for JEV replication, such as prolactin releasing hormone receptor (PRLHR), activating signal cointegrator 1 complex subunit 3 (ASCC3), acyl-CoA synthetase long chain family member 3 (ACSL3), and others. Notably, we found that PRLHR knockdown blocked the autophagic flux, thereby inhibiting JEV infection. Taken together, these findings provide effective data for studying important host factors of JEV replication and scientific data for selecting antiviral drug targets.

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http://dx.doi.org/10.1016/j.vetmic.2024.110099DOI Listing

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