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The hemagglutinin esterase (HE) protein was truncated, and reverse transcription-PCR (RT-PCR) studies confirmed previous work that suggested that the MHV-1 HE is a pseudogene. Targeted recombination was used to select chimeric viruses containing either the MHV-1 S gene or genes encoding all of the MHV-1 structural proteins, on an MHV-A59 background. Challenge studies in mice demonstrated that expression of the MHV-1 S gene within the MHV-A59 background (rA59\/S<jats:sub>MHV-1<\/jats:sub>) increased the pneumovirulence of MHV-A59, and mice infected with this recombinant virus developed pulmonary lesions that were similar to those observed with MHV-1, although rA59\/S<jats:sub>MHV-1<\/jats:sub>was significantly less virulent. Chimeras containing all of the MHV-1 structural genes on an MHV-A59 background were able to reproduce the severe acute respiratory syndrome (SARS)-like pathology observed with MHV-1 and reproducibly increased pneumovirulence relative to rA59\/S<jats:sub>MHV-1<\/jats:sub>, but were still much less virulent than MHV-1. These data suggest that important determinants of pneumopathogenicity are contained within the 3\u2032 one-third of the MHV-1 genome, but additional important virulence factors must be encoded in the genome upstream of the S gene. The severity of the pulmonary lesions observed correlates better with elevated levels of inflammatory cytokines than with viral replication in the lungs, suggesting that pulmonary disease has an important immunological component.<\/jats:p>","DOI":"10.1128\/jvi.00330-10","type":"journal-article","created":{"date-parts":[[2010,7,15]],"date-time":"2010-07-15T02:47:24Z","timestamp":1279162044000},"page":"9278-9291","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Genetic Determinants of Mouse Hepatitis Virus Strain 1 Pneumovirulence"],"prefix":"10.1128","volume":"84","author":[{"given":"Julian L.","family":"Leibowitz","sequence":"first","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&amp;M University System-HSC, College of Medicine, College Station, Texas 77843-1114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Srinivasa","sequence":"additional","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&amp;M University System-HSC, College of Medicine, College Station, Texas 77843-1114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn T.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&amp;M University System-HSC, College of Medicine, College Station, Texas 77843-1114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Ming","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Toronto Transplantation Institute, Toronto, Ontario, Canada M5G 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Wu","sequence":"additional","affiliation":[{"name":"University of Toronto Transplantation Institute, Toronto, Ontario, Canada M5G 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyojeung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Microbial and Molecular Pathogenesis, Texas A&amp;M University System-HSC, College of Medicine, College Station, Texas 77843-1114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Zhong","family":"Ma","sequence":"additional","affiliation":[{"name":"University of Toronto Transplantation Institute, Toronto, Ontario, Canada M5G 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Toronto Transplantation Institute, Toronto, Ontario, Canada M5G 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itay","family":"Shalev","sequence":"additional","affiliation":[{"name":"University of Toronto Transplantation Institute, Toronto, Ontario, Canada M5G 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Smith","sequence":"additional","affiliation":[{"name":"University of Toronto Transplantation Institute, Toronto, Ontario, Canada M5G 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melville J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"University of Toronto Transplantation Institute, Toronto, Ontario, Canada M5G 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary A.","family":"Levy","sequence":"additional","affiliation":[{"name":"University of Toronto Transplantation Institute, Toronto, Ontario, Canada M5G 2N2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"1283","volume":"116","year":"2003","unstructured":"Beijing Group of National for SARS Research Project. 2003. 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