Rapid establishment of a mouse model of MERS-CoV pseudovirus infection based on DPP4 transduction

Abstract

Objective To rapidly establish a mouse model for optical imaging of the dynamical process of pseudotyped Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Methods In vitro expression in HeLa cells and functions of hDPP4 encoded by recombinant adenovirus Ad5 and pseudotyped MERS-CoV were verified. The recombinant adenovirus expressing hDPP4 (Ad5-hDPP4) was injected into BALB/c mice, which were then injected with pseudotyped MERS-CoV expressing firefly luciferase at a titer of 3×107 TCID50 (50% tissue culture infective dose) via intrathoracic (I.T.) or intraperitoneal (I.P.) injection. MERS-CoV infection and tissue distribution were observed using optical imaging techniques. Results hDPP4 and firefly luciferase were efficiently expressed in HeLa cells. In BALB/c mice injected with Ad5-hDPP4 via I. P., firefly luciferase expression were detected in abdomen between 48-96 h after pseudotyped MERS-CoV infection. The expression of firely luciferase was also detected in chests of BALB/c mice injected with Ad5-hDPP4 via I. T. around 48 h after pseudotyped MERS-CoV infection. Conclusions This study reported a simple and rapid method for establishing a mouse model for conveniently and dynamically monitoring pseudotyped MERS-CoV infection, which might provide an effective means for in vivo evaluation of neutralizing antibodies or entry inhibitors by visualization with optical imaging techniques. Key words: Pseudotyped Middle East respiratory syndrome coronavirus; Animal model; Mouse; Firefly luciferase; Optical imaging