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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\u20132 wk after HAV challenge and then subsided despite continuing high hepatic viral RNA. An acute inflammatory response at 3\u20134 wk correlated with the appearance of virus-specific antibodies and apoptosis and proliferation of hepatocytes. 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 significantly longer (35 to &gt;48 wk) than HCV RNA in animals with acute resolving HCV infection (10\u201320 wk). Collectively, these findings 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\u2013host interactions within the liver.<\/jats:p>","DOI":"10.1073\/pnas.1101939108","type":"journal-article","created":{"date-parts":[[2011,6,21]],"date-time":"2011-06-21T01:35:06Z","timestamp":1308620106000},"page":"11223-11228","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":156,"title":["Acute hepatitis A virus infection is associated with a limited type I interferon response and persistence of intrahepatic viral RNA"],"prefix":"10.1073","volume":"108","author":[{"given":"Robert E.","family":"Lanford","sequence":"first","affiliation":[{"name":"Department of Virology and Immunology, Texas Biomedical Research Institute, and"},{"name":"Southwest National Primate Research Center, San Antonio, TX 78227;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongdi","family":"Feng","sequence":"additional","affiliation":[{"name":"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;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Chavez","sequence":"additional","affiliation":[{"name":"Department of Virology and Immunology, Texas Biomedical Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Virology and Immunology, Texas Biomedical Research Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Brasky","sequence":"additional","affiliation":[{"name":"Southwest National Primate Research Center, San Antonio, TX 78227;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunity, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Yamane","sequence":"additional","affiliation":[{"name":"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;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Perelson","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Walker","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunity, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley M.","family":"Lemon","sequence":"additional","affiliation":[{"name":"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;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,6,20]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"383","volume-title":"The Picornaviruses: Molecular Biology, Evolution and Pathogenesis","author":"Feng Z","year":"2010","unstructured":"Z Feng, SM Lemon, Pathogenesis of hepatitis A virus infection. 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