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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA
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Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA

机译：急性甲型肝炎病毒感染与有限的I型干扰素反应和肝内病毒RNA的持续存在有关

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摘要

Hepatitis A virus (HAV) is an hepatotropic human picomavirus that is associated only with acute infection. Its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by quantitative RT-PCR and examining critical aspects of the innate immune response including intrahepatic IFN-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), an hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I IFN-stimulated genes in the liver compared with chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal IFN-stimulated gene 15 and IFIT1 responses peaked 1-2 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute in flammatory response at 3-4 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepa tocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for sig nificantly longer (35 to ＞48 wk) than HCV RNA in animals with acute resolving HCV infection (10-20 wk). Collectively, these find ings indicate that HAV is far stealthier than HCV early in the course of acute resolving infection. HAV infections represent a distinctly different paradigm in virus-host interactions within the liver.
机译：甲型肝炎病毒（HAV）是一种仅与急性感染相关的人类嗜肝性小瘤病毒。它的发病机理尚未得到很好的理解，因为很少有人使用现代方法对动物模型进行研究。我们表征了三只黑猩猩中的HAV感染，通过定量RT-PCR定量了病毒RNA，并检查了包括肝内IFN刺激的基因表达在内的先天免疫应答的关键方面。我们将这些感染状况与受丙型肝炎病毒（HCV）感染的黑猩猩进行了相似的研究，丙肝病毒是一种经常导致持续感染的肝炎性黄病毒。出乎意料的是，尽管具有相似的病毒血症水平和在肝脏中病毒RNA含量高100倍，但与急性解决HCV感染的黑猩猩相比，感染HAV的动物在肝脏中对I型IFN刺激的基因的诱导非常有限。在受到HAV攻击后，最小的IFN刺激基因15和IFIT1反应在1-2周达到峰值，然后尽管肝病毒RNA持续较高，但仍下降。 3-4 wk的急性炎症反应与病毒特异性抗体的出现以及肝细胞的凋亡和增殖有关。尽管如此，HAV RNA在肝脏中持续存在了数月，从血清和粪便清除后仍存在很长时间，并且在三个区室中显示清除动力学存在显着差异。在急性解决HCV感染的动物（10-20周）中，在肝脏中检测到的病毒RNA比HCV RNA长得多（35至＞ 48 wk）。总的来说，这些发现表明，在急性解决感染的早期，HAV的隐身性远高于HCV。 HAV感染代表了肝脏内病毒-宿主相互作用的截然不同的范例。

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  • 作者

    Robert E. Lanford; Zongdi Feng; Deborah Chavez; Bernadette Guerra; Kathleen M. Brasky; Yan Zhou; RDaisuke Yamane; Alan S. Perelson; Christopher M. Walker; Stanley M. Lemon;

  • 作者单位

    Department of Virology and Immunology, Texas Biomedical Research Institute,Southwest National Primate Research Center, San Antonio, TX 78227;

    Division of Infectious Diseases, Department of Medicine, Center for Translational Immunology, and the Lineberger Comprehensive Cancer Center,University of North Carolina, Chapel Hill, NC 27599-7292;

    Department of Virology and Immunology, Texas Biomedical Research Institute;

    Department of Virology and Immunology, Texas Biomedical Research Institute;

    Southwest National Primate Research Center, San Antonio, TX 78227;

    Center for Vaccines and Immunity, Research Institute at Nationwide Children's Hospital, Columbus,OH 43205;

    Division of Infectious Diseases, Department of Medicine, Center for Translational Immunology, and the Lineberger Comprehensive Cancer Center,University of North Carolina, Chapel Hill, NC 27599-7292;

    Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545;

    Center for Vaccines and Immunity, Research Institute at Nationwide Children's Hospital, Columbus,OH 43205;

    Division of Infectious Diseases, Department of Medicine, Center for Translational Immunology, and the Lineberger Comprehensive Cancer Center,University of North Carolina, Chapel Hill, NC 27599-7292;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    innate immunity; viral persistence; immune evasion;

    机译：先天免疫;病毒持久性;免疫逃避;

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