Interferon response genes as immunopathogenic correlates of SARS coronavirus infection in mice (129/S6/SvEv)

To further identify and understand the molecular and immunological correlates of pathology for SARS-CoV infection, we infected 129/S6/SvEv or B129 mice with the TOR2 strain of SARS-CoV. SARS-CoV was detected in the lung and nasal turbinates of infected mice peaking at 1 day post infection (DPI) in both tissues before decreasing rapidly to levels below detection at 7 DPI and 3 DPI, respectively. Pulmonary lesions in virus-infected animals included bronchiolar, peribronchiolar, and perivascular foci of mild to moderate subacute inflammation. Chronic inflammation included inflammatory macrophages, lymphocytes, and plasma cells. Neutralizing antibodies appeared on 5 DPI (IgM); converting to IgG on 7 DPI. Despite the prevailing notion that SARS-CoV interferes with the induction of interferon (IFN) signaling, mice infected with SARS-CoV in vivo demonstrated significantly increased expression of innate antiviral interferon (IFN) response genes (IRGs) in the lungs during the first week of acute infection. By the end of the second week of infection, coordinated expression of MHC class I / II and antigen presentation genes occurred in correlation with declining viral titres. Collectively, the mouse data suggests that robust IFN-driven innate immune responses and a critical shift from innate to adaptive immune responses is necessary for clearance and recovery from SARS-CoV infection. Keywords: time course In this study, we present the characterization of a 4- to 6-week old mouse (129/S6/SvEv) model for SARS-CoV (TOR-2) in conjunction with a functional genomics analysis of the lungs. The study design is a time course (0, 1, 2, 3, 5, 14, 28 days post-infection) examination of the natural history and IFN-mediated host responses in SARS-CoV-infected mice. Three mice are included at each time point for a total of 21 datasets. The Affymetrix Genechip Mouse Genome 430 2.0 Array oligonucleotide array representing approx. 39,000 murine genes was chosen as the microarray platform.