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.
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