Entry Receptor LDLRAD3 Is Required for Venezuelan Equine Encephalitis Virus Peripheral Infection and Neurotropism Leading to Pathogenesis in Mice

Authors

• Natasha M Kafai
• Hana Janova
• Matthew D Cain
• Yael Alippe
• Stefanie Muraro
• Alan Sariol
• Michelle Elam-Noll
• Robyn S Klein
• Michael S Diamond

Language

English

Publication Date

8-29-2023

Journal

Cell Reports

DOI

10.1016/j.celrep.2023.112946

PMID

37556325

PMCID

PMC10529316

PubMedCentral® Posted Date

9-27-2023

PubMedCentral® Full Text Version

Author MSS

Abstract

Venezuelan equine encephalitis virus (VEEV) is an encephalitic alphavirus responsible for epidemics of neurological disease across the Americas. Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3) is a recently reported entry receptor for VEEV. Here, using wild-type and Ldlrad3-deficient mice, we define a critical role for LDLRAD3 in controlling steps in VEEV infection, pathogenesis, and neurotropism. Our analysis shows that LDLRAD3 is required for efficient VEEV infection and pathogenesis prior to and after central nervous system invasion. Ldlrad3-deficient mice survive intranasal and intracranial VEEV inoculation and show reduced infection of neurons in different brain regions. As LDLRAD3 is a determinant of pathogenesis and an entry receptor required for VEEV infection of neurons of the brain, receptor-targeted therapies may hold promise as countermeasures.

Keywords

Animals, Mice, Brain, Central Nervous System, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, Receptors, LDL

Published Open-Access

yes

Recommended Citation

Kafai, Natasha M; Janova, Hana; Cain, Matthew D; et al., "Entry Receptor LDLRAD3 Is Required for Venezuelan Equine Encephalitis Virus Peripheral Infection and Neurotropism Leading to Pathogenesis in Mice" (2023). The Brown Foundation: Institute of Molecular Medicine. 104.
https://digitalcommons.library.tmc.edu/molecular_med/104