ABSTRACT Coronaviruses and influenza viruses are circulating in humans and animals all over the world. Co-infection with these two viruses may aggravate clinical signs. However, the molecular mechanisms of co-infections by these two viruses are incompletely understood. In this study, we applied air-liquid interface (ALI) cultures of well-differentiated porcine tracheal epithelial cells (PTECs) to analyze the co-infection by a swine influenza virus (SIV, H3N2 subtype) and porcine respiratory coronavirus (PRCoV) at different time intervals. Our results revealed that in short-term intervals, prior infection by influenza virus caused complete inhibition of coronavirus infection, while in long-term intervals, some coronavirus replication was detectable. The influenza virus infection resulted in (i) an upregulation of porcine aminopeptidase N, the cellular receptor for PRCoV and (ii) in the induction of an innate immune response which was responsible for the inhibition of PRCoV replication. By contrast, prior infection by coronavirus only caused a slight inhibition of influenza virus replication. Taken together, the timing and the order of virus infection are important determinants in co-infections. This study is the first to show the impact of SIV and PRCoV co- and super-infection on the cellular level. Our results have implications also for human viruses, including potential co-infections by SARS-CoV-2 and seasonal influenza viruses.
【저자키워드】 innate immune response, Co-infection, receptor, viral interference, porcine respiratory coronavirus, porcine aminopeptidase N, super-infection, swine influenza virus, air-liquid interface culture, porcine respiratory disease complex, 【초록키워드】 viruses, SARS-CoV-2, Coronavirus infection, coronavirus, Human, Infection, Influenza virus, molecular mechanism, virus, Replication, Culture, Clinical signs, virus infection, cellular, Air-liquid interface, Coronavirus replication, SIV, epithelial cell, time intervals, determinant, Seasonal influenza, H3N2, upregulation, circulating, intervals, aminopeptidase N, cellular receptor, implication, Respiratory Coronavirus, Complete inhibition, responsible, caused, detectable, applied, tracheal, aggravate, the timing, 【제목키워드】 coronavirus, Infection, Influenza virus, airway epithelial cell,