CD8 + T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome

Coleman, Christopher M.; Sisk, Jeanne M.; Halasz, Gabor; Zhong, Jixin; Beck, Sarah E.; Matthews, Krystal L.; Venkataraman, Thiagarajan; Rajagopalan, Sanjay; Kyratsous, Christos A.; Frieman, Matthew B.

Abstract

© 2016 American Society for Microbiology. Middle East respiratory syndrome coronavirus (MERS-CoV) is an important emerging pathogen that was first described in 2012. While the cell surface receptor for MERS-CoV has been identified as dipeptidyl peptidase 4 (DPP4), the mouse DPP4 homologue does not allow virus entry into cells. Therefore, development of mouse models of MERS-CoV has been hampered by the fact that MERS-CoV does not replicate in commonly available mouse strains. We have previously described a mouse model in which mDPP4 was replaced with hDPP4 such that hDPP4 is expressed under the endogenous mDPP4 promoter. In this study, we used this mouse model to analyze the host response to MERS-CoV infection using immunological assays and transcriptome analysis. Depletion of CD4+ T cells, CD8+ T cells, or macrophages has no effect on MERS-CoV replication in the lungs of infected mice. However, we found that depletion of CD8+ T cells protects and depletion of macrophages exacerbates MERS-CoV-induced pathology and clinical symptoms of disease. Overall, we demonstrate an important role for the inflammatory response in regulating MERS-CoV pathogenesis in vivo.

Citation

Coleman, C. M., Sisk, J. M., Halasz, G., Zhong, J., Beck, S. E., Matthews, K. L., …Frieman, M. B. (2017). CD8 + T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome. Journal of Virology, 91(1), https://doi.org/10.1128/jvi.01825-16

• Journal Article Type: Article
• Acceptance Date: Oct 18, 2016
• Online Publication Date: Oct 26, 2016
• Publication Date: Jan 1, 2017
• Deposit Date: Dec 17, 2019
• Journal: Journal of Virology
• Print ISSN: 0022-538X
• Electronic ISSN: 1098-5514
• Publisher: American Society for Microbiology
• Peer Reviewed: Peer Reviewed
• Volume: 91
• Issue: 1
• DOI: https://doi.org/10.1128/jvi.01825-16
• Public URL: https://nottingham-repository.worktribe.com/output/3589805
• Publisher URL: https://jvi.asm.org/content/91/1/e01825-16