RSV-induced inflammation in the brain

RSV 诱发的大脑炎症

基本信息

  • 批准号:
    10252048
  • 负责人:
  • 金额:
    $ 19.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-02 至 2022-08-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Respiratory syncytial virus (RSV) is a highly contagious pneumovirus that infects over 70% of children under one year of age and nearly 100% of children by age two. Due to the poor immunological memory generated after disease resolution, RSV produces recurrent outbreaks of infection that contribute to viral dissemination in the community. RSV produces various clinical manifestations, ranging from rhinitis and otitis media, to more severe diseases such as pneumonia and bronchiolitis. In addition to the respiratory disease caused by RSV, clinical reports have described the development of neurological symptoms in around 2% of RSV-infected children. Since most children get infected by RSV every year, this fraction of the infected population can represent a significant number of patients. Neurological symptoms include non-febrile seizures, central apnea, lethargy, feeding/swallowing difficulties, muscular tone abnormalities, strabismus, cerebrospinal fluid (CSF) alterations and encephalopathy. Supporting these observations, similar results have been obtained using the murine model of RSV infection including the demonstration that RSV causes viremia and infection of the nervous system (CNS). Strikingly, RSV infected mice and rats show both learning and behavioral alterations after one month of infection. We have described that mice infected by RSV have altered blood brain barrier (BBB) permeability, exhibit increased infiltration of inflammatory cells in the brain and CNS cells, such as astrocytes, are actively infected by RSV. Considering the burden of RSV-infection in children, such a finding is of high interest for public health. However, the pathophysiological mechanisms responsible for RSV dissemination into the CNS and the cognitive/behavioral manifestations remain unknown. We believe that the type of inflammatory response triggered by RSV infection in the lungs favors the development of the CNS alterations. Our studies suggest that RSV is able to infect the CNS and promote cognitive/behavioral impairment due to the alteration of the blood brain barrier (BBB) permeability. Thus, the opening of the BBB could allow RSV and/or the inflammatory cells to infiltrate the brain. Based on these observations, our central hypothesis is that the inflammatory response elicited by RSV infection leads to neurological alterations caused by increased permeability of the BBB, the recruitment of inflammatory cells to the CNS and the infection of nerve cells. The specific aims of this grant will address the pathological processes of RSV infection and its effects on the CNS. This will be achieved by determining the structural and functional changes at the BBB following RSV infection and identifying the brain cells that are infected by RSV, as well as its infection kinetics in mice. The results obtained in this proposal will provide a better understanding of the neuropathology caused by RSV and the possible detrimental effects at the CNS in humans. Moreover, the knowledge of the modulation of the mechanism of RSV brain infection and its host inflammatory response could generate new tools that can help to prevent the consequences of RSV infection over the CNS.
摘要

项目成果

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Steven M Varga其他文献

Steven M Varga的其他文献

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{{ truncateString('Steven M Varga', 18)}}的其他基金

Deciphering the complexities of inflammasome activation following RSV infection
破译 RSV 感染后炎症小体激活的复杂性
  • 批准号:
    10655297
  • 财政年份:
    2022
  • 资助金额:
    $ 19.31万
  • 项目类别:
Deciphering the complexities of inflammasome activation following RSV infection
破译 RSV 感染后炎症小体激活的复杂性
  • 批准号:
    10388682
  • 财政年份:
    2022
  • 资助金额:
    $ 19.31万
  • 项目类别:
Deciphering the complexities of inflammasome activation following RSV infection
破译 RSV 感染后炎症小体激活的复杂性
  • 批准号:
    10807884
  • 财政年份:
    2022
  • 资助金额:
    $ 19.31万
  • 项目类别:
Balancing protection versus immunopathology by RSV-specific memory CD8 T cells
RSV 特异性记忆 CD8 T 细胞平衡保护与免疫病理学
  • 批准号:
    9977905
  • 财政年份:
    2017
  • 资助金额:
    $ 19.31万
  • 项目类别:
Role of TLR4 in Coronavirus Infection
TLR4 在冠状病毒感染中的作用
  • 批准号:
    7860303
  • 财政年份:
    2009
  • 资助金额:
    $ 19.31万
  • 项目类别:
Immunopathology mediated by RSV-specific CD4 T cells
RSV 特异性 CD4 T 细胞介导的免疫病理学
  • 批准号:
    7895292
  • 财政年份:
    2009
  • 资助金额:
    $ 19.31万
  • 项目类别:
Role of TLR4 in Coronavirus Infection
TLR4 在冠状病毒感染中的作用
  • 批准号:
    7701085
  • 财政年份:
    2009
  • 资助金额:
    $ 19.31万
  • 项目类别:
Immunopathology mediated by RSV-specific CD4 T cells
RSV 特异性 CD4 T 细胞介导的免疫病理学
  • 批准号:
    7568970
  • 财政年份:
    2007
  • 资助金额:
    $ 19.31万
  • 项目类别:
Immunopathology mediated by RSV-specific CD4 T cells
RSV 特异性 CD4 T 细胞介导的免疫病理学
  • 批准号:
    8013503
  • 财政年份:
    2007
  • 资助金额:
    $ 19.31万
  • 项目类别:
Immunopathology mediated by RSV-specific CD4 T cells
RSV 特异性 CD4 T 细胞介导的免疫病理学
  • 批准号:
    7758806
  • 财政年份:
    2007
  • 资助金额:
    $ 19.31万
  • 项目类别:

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  • 财政年份:
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