Virology

Antibody

Receptor

Venezuelan equine encephalitis virus

Virus

Biology

Genetics

Alphavirus

Nature

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&nbsp;A domain-containing&nbsp;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&nbsp;1 of LDLRAD3 (LDLRAD3(D1)) is necessary and sufficient to support infection by VEEV, and b...

LDLRAD3 is a receptor for Venezuelan equine encephalitis virus