Ebola virus infection of the female reproductive system
埃博拉病毒感染女性生殖系统
基本信息
- 批准号:10396086
- 负责人:
- 金额:$ 23.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-21 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AbstinenceAfricaAfricanAirAnimal ModelAutomobile DrivingAwarenessBiochemicalBiological AssayBloodCell Differentiation processCellsCessation of lifeCharacteristicsChemotaxisClinicalCoitusConsentCounselingDataDemocratic Republic of the CongoDevelopmentDiseaseDisease OutbreaksEbola Hemorrhagic FeverEbola virusEnvironmentEpithelialEpithelial CellsExperimental ModelsFDA approvedFamilyFamily memberFiloviridae InfectionsFilovirusFlareFollow-Up StudiesGoalsGrantHumanImmuneImmune TargetingImmunocompetentIn VitroInbred BALB C MiceInfectionInflammationInflammation MediatorsInflammatory ResponseInterferonsKnowledgeLaboratoriesLesionLiquid substanceMediatingMethodsModelingMonitorMusOnset of illnessPathogenesisPathogenicityPathway interactionsPatient IsolationPredispositionReportingResearchRoleRouteSeminal fluidSeveritiesSex BehaviorSexual TransmissionSexually Transmitted DiseasesSurvivorsSystemic infectionTestingTherapeuticTimeTissuesVaccinesVaginaViral GenomeViral Hemorrhagic FeversViral PathogenesisViremiaVirusVirus DiseasesVirus ReplicationWomanWorkanti-viral efficacycondomsepidemiologic dataexposure routefemale reproductive systemgenomic datahuman femalehuman modelin vitro Modelin vivoin vivo Modelmalemathematical modelmicrobicidemortalitymouse modelnovelpreventprogramsprophylacticrecruitresponsethree-dimensional modelingtransmission processviral transmission
项目摘要
SUMMARY/ABSTRACT
Ebola virus (family Filoviridae) is the causative agent of Ebola virus disease (EVD), which is characterized by
hemorrhagic fever in humans, reaching high mortality rates (≥40%). Sexual transmission of Ebola virus from a
male survivor to a woman was first documented during the large 2014-2016 West African outbreak. Then this
route of infection was reported to be likely responsible for multiple EBOV outbreak flare-ups between 2015 and
2016. Infectivity of the semen of survivors was later documented for at least 179 days after the onset of disease.
Mathematical modelling of the contribution of sexual behavior in virus transmission during that same outbreak
showed that abstinence, along with infectious patient isolation, could stop an outbreak. As of June 2nd, 2020, the
on-going EBOV outbreak in the Democratic Republic of the Congo describes 3463 cases with 2280 deaths, and
there are no data available as to which route of infection is primarily responsible of transmission and the
situational awareness of survivors to spread EVD. Recently, our group demonstrated that human vaginal
epithelial cells are susceptible to infection with Ebola virus, support productive viral replication resulting in a
robust proinflammatory response. Furthermore, we evaluated the antiviral efficacy of the vaginal Polyphenylene
Carboxymethylene (PPCM) microbicide as a countermeasure and could show suppression of virus replication
and virus-induced inflammatory response in these cells. Altogether, these facts support the critical need to
develop new experimental models for this route of infection and therapeutics preventing virus transmission during
unprotected sexual intercourse.
Our long-term goal is to better understand sexual transmission of Ebola virus, and to identify prophylactic
methods other than condoms. The objective in this proposal is to investigate Ebola virus pathogenesis in women
following sexual transmission using a relevant in-vitro model of the human female reproductive system as well
as a susceptible mouse model. Our central hypothesis is that the human female reproductive system is
susceptible to Ebola virus infection leading to atypical clinical manifestations of EVD and laboratory
characteristics compared to those observed after infection by Ebola virus using other more documented routes
of infection. To interrogate our driving hypothesis, we propose the following Specific Aims: (1) Characterize
Ebola virus infection and inflammation in-vitro using a model of the human vaginal epithelium cultured
at air-liquid interface, (2) Establish an in-vivo model of Ebola Virus Disease (EVD) following intravaginal
virus challenge, and (3) Evaluate the protective antiviral efficacy of PPCM in-vitro and in-vivo. The
proposed studies will develop novel models for research of filovirus pathogenicity and further develop PPCM as
a microbicide for Ebola virus infection.
摘要/摘要
埃博拉病毒(丝状病毒科)是埃博拉病毒病(EVD)的病原体,其特征是
人类出血热,死亡率很高(≥40%)。埃博拉病毒通过性传播
男性幸存者与女性幸存者的首次记录是在 2014-2016 年西非大规模疫情期间。那么这个
据报道,感染途径可能是 2015 年至 2015 年间多次埃博拉病毒爆发的原因。
2016年。后来在疾病发作后至少179天内记录了幸存者精液的传染性。
同一次疫情期间性行为在病毒传播中的贡献的数学模型
研究表明,禁欲和隔离感染患者可以阻止疫情爆发。截至2020年6月2日,
刚果民主共和国正在爆发埃博拉病毒,已有 3,463 例病例,其中 2,280 人死亡,
目前尚无数据表明哪种感染途径是主要传播途径以及传播途径
幸存者的态势感知以传播埃博拉病毒病。最近,我们的研究小组证明,人类阴道
上皮细胞易受埃博拉病毒感染,支持有效的病毒复制,从而导致
强烈的促炎反应。此外,我们评估了阴道聚苯撑的抗病毒功效
羧亚甲基 (PPCM) 杀菌剂作为对策,可以抑制病毒复制
以及病毒引起的这些细胞的炎症反应。总而言之,这些事实支持迫切需要
为这种感染途径开发新的实验模型,并开发预防病毒传播的疗法
无保护的性交。
我们的长期目标是更好地了解埃博拉病毒的性传播,并确定预防措施
避孕套以外的方法。该提案的目的是调查女性埃博拉病毒的发病机制
还使用人类女性生殖系统的相关体外模型进行性传播
作为易感小鼠模型。我们的中心假设是人类女性生殖系统
易受埃博拉病毒感染导致埃博拉病毒病临床表现和实验室表现不典型
与使用其他更有记录的途径感染埃博拉病毒后观察到的特征进行比较
的感染。为了质疑我们的驾驶假设,我们提出以下具体目标:(1)表征
使用培养的人类阴道上皮模型进行体外埃博拉病毒感染和炎症
在气液界面,(2)阴道内注射后建立埃博拉病毒病(EVD)体内模型
病毒攻击,(3) 评估 PPCM 体外和体内的保护性抗病毒功效。这
拟议的研究将开发用于研究丝状病毒致病性的新模型,并进一步将 PPCM 开发为
用于埃博拉病毒感染的杀菌剂。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Susceptibility of BALB/c Mice to a Mouse-Adapted Ebola Virus Intravaginal Infection.
- DOI:10.3390/v15071590
- 发表时间:2023-07-21
- 期刊:
- 影响因子:0
- 作者:Escaffre O;Juelich TL;Smith JK;Zhang L;Bourne N;Freiberg AN
- 通讯作者:Freiberg AN
Characterization of an air-liquid interface primary human vaginal epithelium to study Ebola virus infection and testing of antivirals.
- DOI:10.1016/j.antiviral.2023.105551
- 发表时间:2023-03
- 期刊:
- 影响因子:7.6
- 作者:
- 通讯作者:
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Alexander Niclas Freiberg其他文献
Alexander Niclas Freiberg的其他文献
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{{ truncateString('Alexander Niclas Freiberg', 18)}}的其他基金
Therapeutic efficacy of favipiravir against henipavirus infections
法匹拉韦对亨尼帕病毒感染的治疗效果
- 批准号:
10289470 - 财政年份:2021
- 资助金额:
$ 23.7万 - 项目类别:
Ebola virus infection of the female reproductive system
埃博拉病毒感染女性生殖系统
- 批准号:
10196662 - 财政年份:2021
- 资助金额:
$ 23.7万 - 项目类别:
Role of Reactive Oxygen Species in Nipah Virus Pathogenesis
活性氧在尼帕病毒发病机制中的作用
- 批准号:
8911773 - 财政年份:2014
- 资助金额:
$ 23.7万 - 项目类别:
Bioavailable proteasome inhibitors as broad-spectrum antivirals
生物可利用的蛋白酶体抑制剂作为广谱抗病毒药物
- 批准号:
9091400 - 财政年份:2012
- 资助金额:
$ 23.7万 - 项目类别:
Bioavailable proteasome inhibitors as broad-spectrum antivirals
生物可利用的蛋白酶体抑制剂作为广谱抗病毒药物
- 批准号:
8653759 - 财政年份:2012
- 资助金额:
$ 23.7万 - 项目类别:
Bioavailable proteasome inhibitors as broad-spectrum antivirals
生物可利用的蛋白酶体抑制剂作为广谱抗病毒药物
- 批准号:
8391397 - 财政年份:2012
- 资助金额:
$ 23.7万 - 项目类别:
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