2608. Restriction of Rhinovirus Infection Depends on Virus Sensing and Early IFN Induction

BACKGROUND: Human rhinovirus (RV) infections are ubiquitous, underestimated, and costly. RV causes 3–12 infections per year per individual with a wide range of clinical presentations from mild upper respiratory infections to severe viral pneumonias (1). The virus-host interactions that control RV infection are poorly understood. Thus, there are no vaccines or antiviral medications available. RV infection begins at the airway epithelial surface where the virus first encounters the host cell immune defenses, including type I and III interferon (IFN). IFN actions are critical for defense against RV infection wherein interferon-stimulated genes (ISG)s direct antiviral actions to limit RV infection. METHODS: We hypothesized that the timing of IFN induction is a critical determinant of RV restriction by host innate immune defenses in the human respiratory tract. Thus, an immortalized bronchial epithelial cell line was infected with RV-14 with multiplicity of infection (MOI) ranging from 0.1 – 10 and under conditions of pre/post infection treatment with IFN-β or IFN-λ. Host and viral RNA, protein, and RV infectious particle levels were analyzed. RESULTS: We found that RV infection induces IFN-β and IFN-λ production and subsequent ISG induction, including expression of IFIT-1, OAS1, and MX1. RV-14 infection induced IFN-β and IFN-λ in a dose-dependent manner, with a maximum fold increase of IFN expression at 48hours post infection. ISGs were induced in a similar pattern to IFNs. Viral titers increased significantly over the first 24hours post infection and then plateaued through 96hours. IFN-β and IFN-λ pre- and posttreatment conditions significantly decreased maximum viral titers achieved but with continued viral plateaus 24–96 hours post infection. CONCLUSION: Our observations demonstrate that RV induces innate immune activation and the production of type I and III IFN during acute infection of airway cells. Sustained viral titer plateaus, despite antiviral ISG induction, suggests viral blocking of IFN pathway mechanisms that can be overcome by early IFN induction to significantly restrict RV viral replication. 1. Royston L, Tapparel C. 2016. Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC. Viruses 8. DISCLOSURES: All authors: No reported disclosures.