The robust inflammatory responses caused by MjHKU4r-S mediated cell fusion

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has extremely high virulence and pathogenicity in human, but some MERS-related coronaviruses (bat-CoV HKU4, bat-CoV HKU5-1/2 and MOW15-22/PnNL2018B) showed limited infectivity in human beings. Unlike previously reported MERS-related coronaviruses, the currently identified MERS-related Manis javanica HKU4-related coronavirus (MjHKU4r-CoV-1) exhibited significant infectivity in human cell, organs, and hDPP4-transgenic mice. However, the detailed pathogenic features and underlying mechanisms were unknown. In virological experiments, we found MjHKU4r-CoV-1 triggered extensive syncytia formation by its spike protein (S) and caused significant inflammation responses. Herein, we use RNA sequencing (RNA-Seq) to investigate the transcriptional alterations underlying the robust inflammatory responses caused by S protein mediated syncytia formation.