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

Syndrome.

Coleman CM, et al. J Virol. 2017.

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Abstract

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 IMPORTANCE: The Middle East
respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus that emerged from
zoonotic sources in 2012. Human infections are still occurring throughout Saudi Arabia at a 38% case
fatality rate, with the potential for worldwide spread via air travel. In this work, we identify the host
response to the virus and identify inflammatory pathways and cell populations that are critical for
protection from severe lung disease. By understanding the immune response to MERS-CoV we can
develop targeted therapies to inhibit pathogenesis in the future.

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