Rhinovirus replication and innate immunity in highly differentiated human airway epithelial cells

• Published in: Respiratory research Vol. 20; no. 1; p. 150
• Main Authors: Warner, Stephanie M, Wiehler, Shahina, Michi, Aubrey N, Proud, David
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.07.2019; BioMed Central; BMC
• Subjects: Airway; Cell Differentiation - physiology; Cells, Cultured; Epithelial cells; Health aspects; Highly differentiated human airway epithelial cells; Human rhinovirus; Humans; Immunity (Physiology); Immunity, Innate - physiology; Interferons; Medical research; Negative strand template; Physiological aspects; Respiratory Mucosa - cytology; Respiratory Mucosa - physiology; Respiratory Mucosa - virology; Rhinovirus - physiology; Rhinoviruses; Viperin; Viral clearance; Virus replication; Virus Replication - physiology; Canada; Viperin; Highly differentiated human airway epithelial cells; Negative strand template; Viral clearance; Interferons; Human rhinovirus
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/s12931-019-1120-0

Human rhinovirus (HRV) infections are the primary cause of the common cold and are a major trigger for exacerbations of lower airway diseases, such as asthma and chronic obstructive pulmonary diseases. Although human bronchial epithelial cells (HBE) are the natural host for HRV infections, much of our understanding of how HRV replicates and induces host antiviral responses is based on studies using non-airway cell lines (e.g. HeLa cells). The current study examines the replication cycle of HRV, and host cell responses, in highly differentiated cultures of HBE. Highly differentiated cultures of HBE were exposed to initial infectious doses ranging from 10 to 10 50% tissue culture-infective dose (TCID ) of purified HRV-16, and responses were monitored up to 144 h after infection. Viral genomic RNA and negative strand RNA template levels were monitored, along with levels of type I and II interferons and selected antivirals. Regardless of initial infectious dose, relatively constant levels of both genomic and negative strand RNA are generated during replication, with negative strand copy numbers being10,000-fold lower than those of genomic strands. Infections were limited to a small percentage of ciliated cells and did not result in any overt signs of epithelial death. Importantly, regardless of infectious dose, HRV-16 infections were cleared by HBE in the absence of immune cells. Levels of type I and type III interferons (IFNs) varied with initial infectious dose, implying that factors other than levels of double-stranded RNA regulate IFN induction, but the time-course of HRV-16 clearance HBE was the same regardless of levels of IFNs produced. Patterns of antiviral viperin and ISG15 expression suggest they may be generated in an IFN-independent manner during HRV-16 infections. These data challenge a number of aspects of dogma generated from studies in HeLa cells and emphasize the importance of appropriate cell context when studying HRV infections.