LDLRAD3 is a receptor for Venezuelan equine encephalitis virus.

Nature
Hongming MaMichael S Diamond

Abstract

Venezuelan equine encephalitis virus (VEEV) is a neurotropic alphavirus transmitted by mosquitoes that causes encephalitis and death in humans1. VEEV is a biodefence concern because of its potential for aerosol spread and the current lack of sufficient countermeasures. The host factors that are required for VEEV entry and infection remain poorly characterized. Here, using a genome-wide CRISPR-Cas9-based screen, we identify low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3)-a highly conserved yet poorly characterized member of the scavenger receptor superfamily-as a receptor for VEEV. Gene editing of mouse Ldlrad3 or human LDLRAD3 results in markedly reduced viral infection of neuronal cells, which is restored upon complementation with LDLRAD3. LDLRAD3 binds directly to VEEV particles and enhances virus attachment and internalization into host cells. Genetic studies indicate that domain 1 of LDLRAD3 (LDLRAD3(D1)) is necessary and sufficient to support infection by VEEV, and both anti-LDLRAD3 antibodies and an LDLRAD3(D1)-Fc fusion protein block VEEV infection in cell culture. The pathogenesis of VEEV infection is abrogated in mice with deletions in Ldlrad3, and administration of LDLRAD3(D1)-Fc abolishes disea...Continue Reading

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Citations

Nov 20, 2020·Nature·James Zengel, Jan E Carette
Apr 8, 2021·Cell Reports·James T EarnestMichael S Diamond
Aug 26, 2021·Science China. Life Sciences·Shiyou ZhuWensheng Wei

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Datasets Mentioned

BETA
AAC19322

Methods Mentioned

BETA
flow cytometry
enzyme-linked immunosorbent assay
ELISA
PCR
RAP
transfection
chip
genotyping
FACS

Software Mentioned

cutadapt
MAGeCK
Living Image
GraphPad
GeneWiz
BIAevaluation
Prism

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