West Nile Virus-Induced Expression of Senescent Gene Lgals3bp Regulates Microglial Phenotype within Cerebral Cortex

Author:

Arutyunov Artem12ORCID,Durán-Laforet Violeta3ORCID,Ai Shenjian12ORCID,Ferrari Loris3,Murphy Robert3,Schafer Dorothy P.3,Klein Robyn S.4

Affiliation:

1. Center for Neuroimmunology & Neuroinfectious Diseases, St. Louis, MO 63110, USA

2. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA

3. Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA

4. Department of Microbiology & Immunology, Western Institute of Neuroscience, Schulich School of Medicine & Dentistry, University of Western Ontario, 100 Perth Dr, London, ON N6A 5K8, Canada

Abstract

Microglia, the resident macrophages of the central nervous system, exhibit altered gene expression in response to various neurological conditions. This study investigates the relationship between West Nile Virus infection and microglial senescence, focusing on the role of LGALS3BP, a protein implicated in both antiviral responses and aging. Using spatial transcriptomics, RNA sequencing and flow cytometry, we characterized changes in microglial gene signatures in adult and aged mice following recovery from WNV encephalitis. Additionally, we analyzed Lgals3bp expression and generated Lgals3bp-deficient mice to assess the impact on neuroinflammation and microglial phenotypes. Our results show that WNV-activated microglia share transcriptional signatures with aged microglia, including upregulation of genes involved in interferon response and inflammation. Lgals3bp was broadly expressed in the CNS and robustly upregulated during WNV infection and aging. Lgals3bp-deficient mice exhibited reduced neuroinflammation, increased homeostatic microglial numbers, and altered T cell populations without differences in virologic control or survival. These data indicate that LGALS3BP has a role in regulating neuroinflammation and microglial activation and suggest that targeting LGALS3BP might provide a potential route for mitigating neuroinflammation-related cognitive decline in aging and post-viral infections.

Publisher

MDPI AG

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