权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

"Survivor" neurons drive persistent inflammation following West Nile virus infection

西尼罗河病毒感染后，“幸存者”神经元驱动持续炎症

基本信息

批准号：
10731043
负责人：
Andrew Atwell Oberst
金额：
$ 26.48万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-18 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10731043
关键词：
ATAC-seq Address Apoptosis Arboviruses Brain Cell Death Cell Survival Cells Central Nervous System Cognition Cognitive Cognitive deficits Complex Defect Disease Emerging Technologies Encephalitis Enterobacteria phage P1 Cre recombinase Epigenetic Process Family Flaviviridae Flavivirus Functional disorder Gene Expression Profile Genes Goals Hippocampus Human Immune response Immune signaling Immune system Impaired cognition Individual Infection Inflammation Inflammatory Inflammatory Response Learning Mediating Memory Memory impairment Modeling Motor Mus Neighborhoods Neuroglia Neurons Organism Pathology Pathway interactions Patients Peptide Initiation Factors Property Public Health Recombinants Recovery Research Resistance Role Signal Pathway Signal Transduction Source Stimulus Suicide Survivors System Techniques Testing Tissues Viral Virus Virus Diseases West Nile Encephalitis West Nile viral infection West Nile virus Work insight model organism mortality mosquito-borne mouse model neuronal survival neurotropic virus novel pathogen postmitotic preservation response stressor transcriptomics viral genomics

项目摘要

Project Summary/Abstract- “Survivor” neurons drive persistent inflammation following West Nile virus infection West Nile virus (WNV) is mosquito-borne flavivirus that can infect neurons of the central nervous system. Both human patients murine model organisms that survive neuroinvasive WNV display learning, memory and motor sequelae that persist long after the virus is cleared. While these sequelae have been associated with persistent inflammation within the CNS, the source of this inflammation has remained obscure. Previous studies by our group and others have revealed that neurons are remarkably resistant to programmed cell death in response to multiple stressors, including viral infection. This observation led us to hypothesize that neurons that are infected with WNV but survive and clear infection—“survivor” neurons— sustain virus-induced changes that drive long-term inflammation and CNS disfunction. We sought to test this idea by creating a recombinant clone of WNV that expresses Cre recombinase, then using this virus to mark “survivor” neurons in the brains of WNV-infected mice. Spatial transcriptomic analysis of these cells revealed that “survivor” neurons maintain a robust inflammatory signature weeks after viral infection is cleared. Strikingly, this signature is absent in adjacent, WNV-naïve neurons within the same tissues, supporting the idea that “survivor” neurons are drivers of persistent CNS inflammation. The goal of the work proposed here is to use this newly-developed model to first understand the changes to “survivor” neurons that drive persistent inflammation, and second to assess the consequences of this inflammatory response on the function of these neurons, on nearby cells and on organismal learning and memory. We suggest that the use of these new models and emerging technologies will provide important insight into CNS disfunction caused by WNV infection. We further suggest that this insight may be applicable to long-term virus-induced inflammatory dysfunction in other settings.

项目摘要/摘要-“幸存者”神经元驱动西尼罗河病毒感染后的持续炎症