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Interferon and ribavirin treatment in a rhesus macaque model of novel Middle East respiratory syndrome coronavirus (MERS-CoV) infection (hCoV-EMC)

ABSTRACT: Microarray analysis of lungs (right lower lobe) on day 3 post-infection with MERS-CoV with and without treatment beginning 8 h post-infection with intravenous type I interferon (IFN) and ribavirin (RBV). Dosages are as follows: IFN a2b 5 million IU/kg s.c. q8, RBV loading dose 30mg/kg i.v.; Maintenance doses: IFN 5 MIU/kg s.c. q16; RBV, 10mg/kg i.m. q8.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE47957 | GEO | 2013/09/06

SECONDARY ACCESSION(S): PRJNA208496

REPOSITORIES: GEO

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Project description:Background: Type I interferons (IFNs) are essential to the clearance of viral diseases, in part by initiating upregulation of IFN regulated genes (IRGs). A clear distinction between genes upregulated directly by virus and genes upregulated by secondary IFN production has not been made. Here we investigated the genes regulated by IFN-a2b compared to the genes regulated by SARS-CoV infection in ferrets. Methods: We characterized early host immune responses in peripheral blood and lung necropsies of ferrets injected with IFN-a2b or infected with SARS-CoV/Tor 2 strain, using microarray analysis on the Affymetrix platform. Results: We identified a common IRG signature that was upregulated in both SARS-CoV infected ferrets as well as in ferrets injected with IFN-a2b. We also identified unique patterns of gene expression for leukocyte activation, cell adhesion and complement pathways between IFN-a2b injection and SARS-CoV infection. Conclusions: Our results define the effects of IFN-a2b on the immune system of ferrets highlighting genes regulated by IFN during SARS-CoV infection. We have shown the similarities and differences of top funcional gene groups as well as pathways that play key roles in early immune responses in ferrets in response to IFN-a2b or SARS-CoV. Key words: ferret, gene expression, SARS, interferon. Keywords: time course In experiments with IFN-a2b, for peripheral blood, 15 ferrets were randomly allocated to 3 groups: Day 0, 5 ferrets (no IFN injection), day 1, 6 ferrets (injected), and day 2, 4 ferrets (injected). For lung necropsies of injected ferrets with IFN-a2b, we used 12 ferrets in 3 groups: 4 ferrets, day 0 (no IFN injection), 4 ferrets, day 1 (injected) and 4 ferrets, day 2 (injected). Experimental groups for SARS-CoV infection was as follows: For peripheral blood, 3 and 4 ferrets for day 0 (no infection) and day 2 (infection) respectively. For lung neceropsies, a total of 9 ferrets in 3 groups, each with 3 replicates for day 0 (no infection), day 1 (infection) and day 2 (infection).

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Interferon and ribavirin treatment in a rhesus macaque model of novel Middle East respiratory syndrome coronavirus (MERS-CoV) infection (hCoV-EMC)

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