Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease

• DOI: 10.1128/jvi.02009-15
• Publication Date: 2015-10-08T02:18:53Z
• Authors: Xinrong Tao; Tania Garron; Anurodh Shankar A...; Abdullah Algaissi; Bi-Hung Peng; Maki Wakamiya; Teh-Sheng Chan; Lu Lu; Lanying Du; Shibo Jiang; Robert B. Couch; Chien-Te K. Tseng
• Keywords: Histopathology; Coronavirus; Pathogenesis; Infectious dose

Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model MERS-CoV infection disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) (LD50) virus were estimated to be <1 10 TCID50 MERS-CoV, respectively. Neutralizing antibody developed in surviving mice from ID50/LD50 determinations, all fully immune challenge with 100 LD50 MERS-CoV. tissue distribution histopathology challenged potential working subsequently evaluated. In contrast overwhelming seen 10(5) able recover these only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early persistent lung delayed occurrence brain infection. Persistent inflammatory infiltrates lungs stems at day 2 6 after infection, While focal also noted liver, definite pathology was not other tissues. Finally, using receptor binding domain protein vaccine fusion inhibitor, demonstrated value this vaccines antivirals against MERS. As outcomes patients differ greatly, ranging asymptomatic death, having available both an makes relevant advancing MERS research.