Abstract

Severe acute respiratory syndrome (SARS) is a potentially fatal disease that appears to have originated in the Guandong Province of China in the fall of 2002. The disease is caused by a new human coronavirus (CoV), named the SARS-CoV, which is unlike any previous known coronavirus, but classified among the group II coronaviruses like MHV. The goals of this proposal include the systematic deletion of each accessory ORF singly and then in combinations of the accessory ORFs of the SARS-CoV. I will use these deletion mutants to test the hypothesis that one or more accessory ORFs are responsible for modulating the host innate immune response. I will analyze the anti-viral response in Caco2, MA104 and Human Airway Epithelial (HAE) cells to establish at what level in the anti-viral pathway the interferon-antagonist proteins of SARS are acting, as well as how mutants in these SARS genes effect pathogenesis. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI066542-01
Application #
6997685
Study Section
Special Emphasis Panel (ZRG1-F13 (20))
Program Officer
Cassels, Frederick J
Project Start
2005-08-01
Project End
2008-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
1
Fiscal Year
2005
Total Cost
$43,956
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Frieman, Matthew; Yount, Boyd; Agnihothram, Sudhakar et al. (2012) Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J Virol 86:884-97
Frieman, Matthew B; Chen, Jun; Morrison, Thomas E et al. (2010) SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism. PLoS Pathog 6:e1000849
Zornetzer, Gregory A; Frieman, Matthew B; Rosenzweig, Elizabeth et al. (2010) Transcriptomic analysis reveals a mechanism for a prefibrotic phenotype in STAT1 knockout mice during severe acute respiratory syndrome coronavirus infection. J Virol 84:11297-309
Frieman, Matthew; Ratia, Kiira; Johnston, Robert E et al. (2009) Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling. J Virol 83:6689-705
Frieman, Matthew; Heise, Mark; Baric, Ralph (2008) SARS coronavirus and innate immunity. Virus Res 133:101-12
Frieman, Matthew; Yount, Boyd; Heise, Mark et al. (2007) Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J Virol 81:9812-24
Kopecky-Bromberg, Sarah A; Martinez-Sobrido, Luis; Frieman, Matthew et al. (2007) Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol 81:548-57