Resolution of acute hepatitis B virus infections

解决急性乙型肝炎病毒感染

• 批准号: nhmrc : 453505
• 负责人: A/Pr Allison Jilbert
• 金额: $ 24.28万
• 依托单位: The University of Adelaide
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/resolution-acute-hepatitis-virus-infections/98697
• 关键词: Resolution; acute; hepatitis; virus; infections

Though vaccination has had a major impact on the number of persons becoming infected, chronic infection with the hepatitis B virus (HBV) still remains a major worldwide problem, with 350 million people chronically infected. The existence of HBV vaccine escape mutants and the fact that 5% of vaccinees fail to respond implies that HBV will remain a significant public health problem for the foreseeable future. Current treatments for chronic HBV infection have a low success rate (~20%) and patients with chronic infection are expected to die prematurely due to chronic liver disease or primary liver cancer. Interestingly, exposure to HBV can lead to either acute resolving or chronic HBV infection. Like chronic infections, acute infections involve spread of virus to virtually every hepatocyte, followed by rapid clearance of the virus mediated by the host immune response. Our immediate aim is to study the resolution of acute HBV infections to determine how the stable intracellular viral genome, covalently closed circular DNA (cccDNA), is cleared from the nucleus of infected hepatocytes. Our broad long-term aim is to develop new and effective treatments for chronic HBV infection based on a better understanding of how acute HBV infections are resolved by the host. Based on our previous work we believe that clearance of cccDNA requires hepatocyte death, together with compensatory proliferation of other infected hepatocytes. We will perform detailed studies in duck hepatitis B virus (DHBV) infected ducks to determine if hepatocyte death and compensatory proliferation are essential to clear the infection, or if mechanisms exist for clearance that do not involve cell destruction.

虽然疫苗接种对感染人数产生了重大影响，但B型肝炎病毒（HBV）的慢性感染仍然是一个主要的世界性问题，有3.5亿人慢性感染。HBV疫苗逃逸突变体的存在以及5%的接种者未能应答的事实意味着HBV在可预见的未来仍将是一个重大的公共卫生问题。目前治疗慢性HBV感染的成功率较低（约20%），慢性感染患者预计会因慢性肝病或原发性肝癌而过早死亡。有趣的是，暴露于HBV可导致急性消退或慢性HBV感染。与慢性感染一样，急性感染涉及病毒扩散到几乎每个肝细胞，随后由宿主免疫应答介导的病毒快速清除。我们的直接目标是研究急性HBV感染的解决方案，以确定稳定的细胞内病毒基因组，共价闭合环状DNA（cccDNA），是如何从感染的肝细胞核中清除的。我们广泛的长期目标是在更好地了解宿主如何解决急性HBV感染的基础上，开发新的有效治疗慢性HBV感染的方法。基于我们之前的工作，我们认为cccDNA的清除需要肝细胞死亡，以及其他感染肝细胞的代偿性增殖。我们将在鸭肝炎B病毒（DHBV）感染的鸭中进行详细的研究，以确定肝细胞死亡和代偿性增殖是否对清除感染至关重要，或者是否存在不涉及细胞破坏的清除机制。