ENTEROVIRUS INFECTIONS OF THE PLACENTA AND FETUS
胎盘和胎儿的肠道病毒感染
基本信息
- 批准号:2200573
- 负责人:
- 金额:$ 8.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-09-01 至 1996-08-31
- 项目状态:已结题
- 来源:
- 关键词:Enterovirus communicable disease transmission disease /disorder model embryo /fetus encephalitis virus encephalomyelitis gestational age host organism interaction immunocytochemistry immunotherapy in situ hybridization laboratory mouse model design /development mutant placenta virus cytopathogenic effect virus infection mechanism
项目摘要
Enteroviruses (EVs) are ubiquitous viruses which pose a
significant risk to human pregnancies. In utero infections may lead to
maternal illness; neonatal illnesses, including meningoencephalitis,
myocarditis, hepatitis, and/or sepsis; premature delivery; fetal
myocarditis and death; fetal hepatic and adrenal necrosis and demise; and
congenital malformations of the cardiovascular, gastrointestinal,
genitourinary, and central nervous systems. The pathogenesis of these
gestational infections is poorly understood. The proposed project will
investigate the significance of transplacental EV infection, the
mechanisms employed by the placenta to protect against fetal infection,
and factors which may cause those mechanisms to break down. The effects
of intrauterine EV infection on the placenta and fetus will be
elucidated, and factors influencing fetal outcome will be delineated.
Immunologic and pharmacologic strategies to prevent fetal morbidity
associated with EV infections will be evaluated.
Studies will be performed in a murine model of gestational EV
infection which utilizes a natural EV of mice, Theiler's murine
encephalomyelitis virus (TMEV). In this model, placentas and fetuses are
readily infected following maternal inoculation with TMEV in early
gestation, while in late gestation, placentas are infected but the fetus
is never infected. Experiments will be performed in this model to
determine whether the evolution of this placental barrier to viral
transmission is based on anatomic and structural features (examining
placentas containing virus and placentas containing inert particles of
similar size by electron microscopy), immunologic phenomena (studying
infected placentas with immunohistochemistry and studying viral infection
of distinct placental cell populations in vitro), and/or changes in
placental cell susceptibility to viral infection (employing placental
cell culture techniques). Morphologic studies, tissue culture, in situ
hybridization, and immunohistochemistry will be used to elucidate the
effects of TMEV infection on the placenta and the fetus. Host and viral
factors which may affect the rate of transplacental infection and/or the
outcome of fetal infection will be assessed by varying maternal
physiologic parameters (age, physical stress, nutrition, uteroplacental
blood flow) and by studying viral mutants in this model. Finally,
immunologic and pharmacologic strategies to prevent transplacental
infection and/or prevent adverse outcome of fetal infection will be
tested in this animal model. These studies will shed light on protective
mechanisms employed by the human placenta, effects of EVs on human
fetuses, and possible treatment strategies for human pregnancies at risk.
The results will have relevance not only for EV infections, but also for
infections by other viruses which threaten the human fetus.
肠道病毒(EV)是普遍存在的病毒,
对人类怀孕有很大的风险。 子宫内感染可能导致
产妇疾病;新生儿疾病,包括脑膜脑炎,
心肌炎、肝炎和/或败血症;早产;胎儿
心肌炎和死亡;胎儿肝脏和肾上腺坏死和死亡;以及
先天性心血管畸形,胃肠畸形,
泌尿生殖系统和中枢神经系统。 这些疾病的发病机制
对妊娠期感染知之甚少。 拟议项目将
探讨经胎盘EV感染的意义,
胎盘保护胎儿免受感染的机制,
以及可能导致这些机制崩溃的因素。 的影响
胎盘和胎儿的宫内EV感染将
阐明,影响胎儿结局的因素将被描述。
预防胎儿发病的免疫学和药理学策略
将评估与EV感染相关的风险。
研究将在妊娠EV的小鼠模型中进行
利用小鼠的天然EV的感染,Theiler小鼠
脑脊髓炎病毒(TMEV)。 在这个模型中,胎盘和胎儿
母亲接种TMEV后,
妊娠,而在妊娠后期,胎盘被感染,但胎儿
从未被感染。 将在该模型中进行实验,
确定胎盘屏障的演变是否会导致病毒感染
传播是基于解剖和结构特征(检查
含有病毒的胎盘和含有病毒的惰性颗粒的胎盘
电子显微镜下相似的大小),免疫学现象(研究
感染胎盘的免疫组化和研究病毒感染
不同的胎盘细胞群),和/或
胎盘细胞对病毒感染的易感性(采用胎盘
细胞培养技术)。 形态学研究,组织培养,原位
杂交和免疫组织化学将用于阐明
TMEV感染对胎盘和胎儿的影响。 宿主和病毒
可能影响经胎盘感染率和/或
胎儿感染的结果将通过不同的母体
生理参数(年龄、身体应激、营养、子宫胎盘
血液流动),并通过研究该模型中的病毒突变体。 最后,
预防经胎盘感染免疫学和药理学策略
感染和/或预防胎儿感染不良后果,
在这个动物模型中测试。 这些研究将揭示保护性
人类胎盘的作用机制,EV对人类胎盘的影响,
胎儿,以及可能的治疗策略,为人类怀孕的风险。
这些结果不仅与EV感染有关,
其他威胁人类胎儿的病毒感染。
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)
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{{ truncateString('MARK J ABZUG', 18)}}的其他基金
PACTG P1061S: EVALUATION OF IMMUNOLOGIC MEMORY FOLLOWING PNEUMOCOCCAL, HEP B
PACTG P1061S:肺炎球菌、乙型肝炎后的免疫记忆评估
- 批准号:
7605120 - 财政年份:2007
- 资助金额:
$ 8.66万 - 项目类别:
P1024: PNEUMOCOCCAL CONJUGATE VACCINE & IMMUNIZATIONS IN HIV TREATED W/HAART
P1024:肺炎球菌结合疫苗
- 批准号:
7202395 - 财政年份:2005
- 资助金额:
$ 8.66万 - 项目类别:
PNEUMOCOCCAL CONJUGATE VACCINE & IMMUNIZATIONS IN HIV TX
肺炎球菌结合疫苗
- 批准号:
7041017 - 财政年份:2004
- 资助金额:
$ 8.66万 - 项目类别:
ENTEROVIRUS INFECTIONS: INTRAUTERINE, PLACENTAL PROTECTION & NEONATAL THERAPY
肠道病毒感染:宫内、胎盘保护
- 批准号:
3908019 - 财政年份:
- 资助金额:
$ 8.66万 - 项目类别: