Modulation of the innate immune response by Middle East Respiratory Syndrome Coronavirus Spike protein
Al Rashdi, Mohmed Abdulla Omar
Cardiff Metropolitan University
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Background: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as an emerging pathogen linked to patients presenting with serious respiratory illness complicated with renal impairment and to a lesser extent gastrointestinal and central nervous symptom. High mortality that can reach more than 40% was noted, in particular among elderly patients with co-morbidities. Up to date MERS cases have been linked to the Middle East, but MERS-CoV is considered a potential pandemic agent with no licensed vaccine available. The pathogenesis of MERS-CoV is not fully understood. Studies have shown that ciliated and non-ciliated respiratory epithelial cells and pulmonary blood vessels endothelial cells although susceptible to MERS-CoV infection, do not elicit a strong inflammatory response. Monocyte-derived macrophages and dendritic cells are also susceptible to the virus with each displaying unique inflammatory responses. It has been confirmed that MERS-CoV enters the target cell using the viral surface Spike (S) protein by interacting with its cellular receptor dipeptidyl peptidase 4 (DPP4). The presence of this receptor on keratinocytes potentially make them vulnerable to MERS-CoV infection. However, little is known about the interaction of MERS-CoV with keratinocytes and in particular how these cells interact with the S protein. Aim: The main objective of the present work was to look at the interaction between MERS-CoV S protein and human keratinocytes. Methodology: HaCaT keratinocytes were stimulated with commercially available recombinant MERS-CoV spike (rS) protein and the production and release of CXCL8/ IL-8 by stimulated and non-stimulated HaCaT cells was measured using an Enzyme- Linked Immuno Sorbent Assay (ELISA) test. Main findings and conclusion: The work presented here shows that MERS-CoV rS protein has the capacity to stimulate the production of CXCL8 /IL-8 by keratinocytes in a dose-response manner. Moreover, MERS-CoV rS protein can modulate the production of this chemokine when used in combination with synthetic microbial compounds such as poly I:C and Pam2CSK4. When combined with poly I:C, the levels of CXCL8 /IL-8 increased above those detected with poly I:C alone. On the contrary, when MERS-CoV rS protein was used in combination with Pam2CSK4 the release of CXCL8/IL-8 was reduced. Characterization of the interaction between keratinocytes and MERS CoV rS protein warrants more studies as the results presented could help explain the weak inflammatory responses already reported and influence the development of vaccines prepared using recombinant proteins combined with synthetic microbial components used as adjuvants.
Biomedical science (BSc)
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