INNATE AND ADAPTIVE IMMUNE RESPONSE TO HAV

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 甲型肝炎病毒（HAV）是NIAID B类优先因子，可能是全球感染性黄疸的最常见原因，尽管在暴露于病毒之前或甚至之后接种有效疫苗可以预防肝病。 在包括美国在内的许多国家，HAV感染率已经通过广泛的儿童疫苗接种而降低，但大规模食物或水传播HAV爆发的可能性仍然存在。对这种病毒的天然免疫力知之甚少。HAV感染通常在感染后5-7周内清除。 复发性肝炎可在症状消退后4-16周内发生。尽管复发的可能性可以延长肝脏疾病长达一年，但HAV不能像HCV那样建立持续感染，HCV是一种黄病毒，在约70%的感染者中引起慢性肝炎。 这是一个相对短期的试点研究，以了解甲型肝炎病毒的保护性免疫反应的性质。 我们的计划是用100 CID（黑猩猩感染剂量）的HAV HM 175毒株静脉内攻击两只动物。 然后将在血液和肝脏中监测天然和适应性免疫力6个月，如下文提供的样品和程序表所述。 动物将在攻毒后约5-8周终止感染。 这项研究可能会提供深入了解肝脏中成功的病毒免疫机制，这种机制与人类高度相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Hepatitis A virus (HAV), a NIAID Category B priority agent, is perhaps the most common cause of infectious jaundice globally despite the availability of an effective vaccine that can prevent liver disease when administered before or even after exposure to the virus. HAV infection rates in many countries including the United States have been reduced by widespread childhood vaccination but the potential for large-scale food or waterborne HAV outbreaks remains. Natural immunity to this virus is poorly understood. HAV infection is usually cleared within 5-7 weeks of infection. Relapsing hepatitis can occur within 4-16 weeks of symptom resolution in some individuals. Despite the potential for relapse that can prolong liver disease for up to one year, HAV cannot establish persistent infection like HCV, a flavivirus that causes chronic hepatitis in about 70% of infected individuals. This is a relatively short-term pilot study to understand the nature of protective immune responses to the hepatitis A virus. Our plan is to challenge two animals intravenously with 100 CID (chimpanzee infectious does) of HAV HM175 strain. Innate and adaptive immunity will then be monitored in blood and liver for 6 months as described in the Table of Samples and Procedures provided below. The animals will terminate the infection, approximately 5-8 weeks after challenge. The study may provide insight into mechanisms of successful viral immunity in the liver in a species that is highly relevant to humans.