Role of Host Cell Factors in Newborn Herpes Simplex Virus (HSV) Encephalitis
宿主细胞因子在新生儿单纯疱疹病毒 (HSV) 脑炎中的作用
基本信息
- 批准号:9890025
- 负责人:
- 金额:$ 32.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAgeAntiviral ResponseAstrocytesBenignBiological AssayBirthBlood - brain barrier anatomyBrainCell SeparationCellsCellular TropismCentral Nervous System DiseasesCentral Nervous System Viral DiseasesChildClustered Regularly Interspaced Short Palindromic RepeatsDataDevelopmentDiseaseEncephalitisExhibitsExpression ProfilingFlow CytometryFluoresceinGene ExpressionGenetic studyHerpesvirus 1IFNAR1 geneImmune responseImmunofluorescence ImmunologicIn VitroIncidenceInfectionInfiltrationInnate Immune ResponseIntegration Host FactorsInterferon Type IInterferon-alphaInterferon-betaInterferonsKnockout MiceMediatingMessenger RNAMicrogliaMicrospheresModelingMorbidity - disease rateMucous MembraneMusMutationNeonatalNeonatal MortalityNeuraxisNeurogliaNeurologicNeurological outcomeNeuronsNeurotropismNewborn InfantOutcomePathogenesisPathway interactionsPlayPopulationPredispositionPrimary Cell CulturesProductionProteinsRoleSeroprevalencesSeveritiesSeverity of illnessSignal PathwaySignal TransductionSimplexvirusStructure of choroid plexusSurvivorsTarget PopulationsTropismUnited StatesViralViral EncephalitisViral PathogenesisVirus DiseasesVirus ReplicationWorkage groupage relatedbaseblood-brain barrier permeabilizationcytokineexperimental studyhigh riskimmunomodulatory therapiesimprovedimproved outcomeinnate immune mechanismsinsightmortalitymouse modelneonatal immune systemneonatal infectionneonatal morbidityneurodevelopmentneurotropicneurotropic viruspathogenpreventreceptorrecombinase-mediated cassette exchangeresponsesmall hairpin RNAsurvival outcomevirus tropism
项目摘要
PROJECT SUMMARY
The newborn brain is uniquely susceptible to a wide range of pathogens compared to the adult, and this
is exemplified following infection with herpes simplex virus type-1 (HSV-1), the most common cause of viral
encephalitis. The majority of newborns infected with HSV-1 will go on to have severe disease, including viral
dissemination and encephalitis, whereas infection in the adult population typically results in asymptomatic
acquisition or benign mucosal infection. HSV encephalitis in the adult remains rare despite a HSV-1
seroprevalence of 50-80% in this population. The significantly different outcomes between adults and
newborns following HSV infection suggest an age-dependent difference in susceptibility to central nervous
system (CNS) disease based on host factors. A relative immaturity of the neonatal immune system is
commonly implicated in their overall increased susceptibility to HSV and other neurotropic viruses, however,
the precise reasons underlying their increased susceptibility to viral encephalitis remain unknown. The
incomplete understanding of pathogenesis in the neonatal population remains as a critical barrier to improving
survival and neurologic outcomes following HSV encephalitis.
In this proposal, we plan to investigate the innate immune mechanisms in the brain responsible for
differences in susceptibility and severity of HSV disease between the newborn and adult. We will build on our
previously unfunded work to understand the role of the host response in determining viral tropism within the
brain, the contribution of glial cells to HSV-1 infection, and modulation of the blood brain barrier (BBB) by type I
interferon (IFN) signaling in the newborn during infection. HSV-1 and the host antiviral response has been
frequently studied in the context of neuronal infection, however, there is an emerging role for astrocytes and
microglia in the pathogenesis of viral encephalitis. Preliminary data from our lab demonstrates astrocytic
infection in the newborn brain in addition to neurons, and significant differences in the type I IFN response
between the two age groups. We hypothesize that the contribution of astrocytes and microglia to viral
replication and survival following HSV encephalitis is age-dependent. Our proposed studies will demonstrate
the contribution of type I IFN signaling specifically in astrocytes and microglia to HSV pathogenesis, and how
this response changes through different developmental ages. HSV encephalitis often occurs in the context of
disseminated disease in the newborn, and we also plan to investigate the role of type I IFN in modulating the
BBB during infection and its contribution to HSV spread to the brain. Preliminary data from our lab suggests
that type I IFN treatment improves survival and reduces HSV neuroinvasion during disseminated disease. In
this proposal, we will pursue the innate immune mechanisms that underlie BBB modulation in the newborn
brain, and elucidate the potential of immunomodulatory therapy to improve outcomes in this age group.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Richard M Longnecker其他文献
Richard M Longnecker的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Richard M Longnecker', 18)}}的其他基金
Receptor Usage and Regulation of the Immune Response in HSV Infection
HSV 感染中受体的使用和免疫反应的调节
- 批准号:
10738934 - 财政年份:2023
- 资助金额:
$ 32.9万 - 项目类别:
Role of Host Cell Factors in Newborn Herpes Simplex Virus (HSV) Encephalitis
宿主细胞因子在新生儿单纯疱疹病毒 (HSV) 脑炎中的作用
- 批准号:
10133167 - 财政年份:2019
- 资助金额:
$ 32.9万 - 项目类别:
Role of Host Cell Factors in Newborn Herpes Simplex Virus (HSV) Encephalitis
宿主细胞因子在新生儿单纯疱疹病毒 (HSV) 脑炎中的作用
- 批准号:
10369050 - 财政年份:2019
- 资助金额:
$ 32.9万 - 项目类别:
Role of Host Cell Factors in Newborn Herpes Simplex Virus (HSV) Encephalitis
宿主细胞因子在新生儿单纯疱疹病毒 (HSV) 脑炎中的作用
- 批准号:
10589755 - 财政年份:2019
- 资助金额:
$ 32.9万 - 项目类别:
Role of Host Cell Factors in Herpes Simplex Virus (HSV) Keratitis
宿主细胞因子在单纯疱疹病毒 (HSV) 角膜炎中的作用
- 批准号:
8029319 - 财政年份:2011
- 资助金额:
$ 32.9万 - 项目类别:
Role of Host Cell Factors in Herpes Simplex Virus (HSV) Keratitis
宿主细胞因子在单纯疱疹病毒 (HSV) 角膜炎中的作用
- 批准号:
8232012 - 财政年份:2011
- 资助金额:
$ 32.9万 - 项目类别:
Discovery of New Treatment Options for EBV-associated Lymphoma and PTLD
发现 EB 病毒相关淋巴瘤和 PTLD 的新治疗方案
- 批准号:
8245223 - 财政年份:2008
- 资助金额:
$ 32.9万 - 项目类别:
Discovery of New Treatment Options for EBV-associated Lymphoma and PTLD
发现 EB 病毒相关淋巴瘤和 PTLD 的新治疗方案
- 批准号:
8267730 - 财政年份:2008
- 资助金额:
$ 32.9万 - 项目类别:
DETERMINATION OF THE IMPORTANCE OF LMP2A IN PRIMARY EBV INFECTION
确定 LMP2A 在原发 EBV 感染中的重要性
- 批准号:
7715494 - 财政年份:2008
- 资助金额:
$ 32.9万 - 项目类别:
Discovery of New Treatment Options for EBV-associated Lymphoma and PTLD
发现 EB 病毒相关淋巴瘤和 PTLD 的新治疗方案
- 批准号:
8076396 - 财政年份:2008
- 资助金额:
$ 32.9万 - 项目类别:
相似海外基金
Developing a Young Adult-Mediated Intervention to Increase Colorectal Cancer Screening among Rural Screening Age-Eligible Adults
制定年轻人介导的干预措施,以增加农村符合筛查年龄的成年人的结直肠癌筛查
- 批准号:
10653464 - 财政年份:2023
- 资助金额:
$ 32.9万 - 项目类别:
Doctoral Dissertation Research: Estimating adult age-at-death from the pelvis
博士论文研究:从骨盆估算成人死亡年龄
- 批准号:
2316108 - 财政年份:2023
- 资助金额:
$ 32.9万 - 项目类别:
Standard Grant
Determining age dependent factors driving COVID-19 disease severity using experimental human paediatric and adult models of SARS-CoV-2 infection
使用 SARS-CoV-2 感染的实验性人类儿童和成人模型确定导致 COVID-19 疾病严重程度的年龄依赖因素
- 批准号:
BB/V006738/1 - 财政年份:2020
- 资助金额:
$ 32.9万 - 项目类别:
Research Grant
Transplantation of Adult, Tissue-Specific RPE Stem Cells for Non-exudative Age-related macular degeneration (AMD)
成人组织特异性 RPE 干细胞移植治疗非渗出性年龄相关性黄斑变性 (AMD)
- 批准号:
10294664 - 财政年份:2020
- 资助金额:
$ 32.9万 - 项目类别:
Sex differences in the effect of age on episodic memory-related brain function across the adult lifespan
年龄对成人一生中情景记忆相关脑功能影响的性别差异
- 批准号:
422882 - 财政年份:2019
- 资助金额:
$ 32.9万 - 项目类别:
Operating Grants
Modelling Age- and Sex-related Changes in Gait Coordination Strategies in a Healthy Adult Population Using Principal Component Analysis
使用主成分分析对健康成年人群步态协调策略中与年龄和性别相关的变化进行建模
- 批准号:
430871 - 财政年份:2019
- 资助金额:
$ 32.9万 - 项目类别:
Studentship Programs
Transplantation of Adult, Tissue-Specific RPE Stem Cells as Therapy for Non-exudative Age-Related Macular Degeneration AMD
成人组织特异性 RPE 干细胞移植治疗非渗出性年龄相关性黄斑变性 AMD
- 批准号:
9811094 - 财政年份:2019
- 资助金额:
$ 32.9万 - 项目类别:
Study of pathogenic mechanism of age-dependent chromosome translocation in adult acute lymphoblastic leukemia
成人急性淋巴细胞白血病年龄依赖性染色体易位发病机制研究
- 批准号:
18K16103 - 财政年份:2018
- 资助金额:
$ 32.9万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Doctoral Dissertation Research: Literacy Effects on Language Acquisition and Sentence Processing in Adult L1 and School-Age Heritage Speakers of Spanish
博士论文研究:识字对西班牙语成人母语和学龄传统使用者语言习得和句子处理的影响
- 批准号:
1823881 - 财政年份:2018
- 资助金额:
$ 32.9万 - 项目类别:
Standard Grant
Adult Age-differences in Auditory Selective Attention: The Interplay of Norepinephrine and Rhythmic Neural Activity
成人听觉选择性注意的年龄差异:去甲肾上腺素与节律神经活动的相互作用
- 批准号:
369385245 - 财政年份:2017
- 资助金额:
$ 32.9万 - 项目类别:
Research Grants