Upper Respiratory Tract OC43 Infection Model for Investigating Airway Immune-modifying Therapies

Am J Respir Cell Mol Biol. 2023 Aug 21. doi: 10.1165/rcmb.2023-0202MA. Online ahead of print.ABSTRACTRespiratory virus infections initiate and transmit from the upper respiratory tract (URT). Coronaviruses, including OC43, are a major cause of respiratory infection and disease. Failure to mount an effective anti-viral immune response in the nasal mucosa increases the risk of severe disease and person to person transmission highlighting the need for URT infection models to support development of nasal treatments that improve coronavirus anti-viral immunity. We aimed to determine if OC43 productively infected the mouse URT and would therefore be a suitable model to assess the efficacy and mechanism of action of nasal-targeting immune-modifying treatments. We administered OC43 via intranasal inoculation to wild type BALB/c mice and assessed virus airway tropism (by comparing total respiratory tract- to URT-only-virus exposure) and characterized infection-induced immunity by quantifying specific anti-viral cytokines and performing gene array assessment of immune genes. We then assessed the effect of immune-modulating therapies including immune-stimulating TLR2/6 agonist (INNA-X) and immune-suppressing corticosteroid fluticasone propionate (FP). OC43 replicated in nasal respiratory epithelial cells with peak viral RNA observed two days post-infection. Prophylactic treatment with INNA-X accelerated expression of virus-induced interferon (IFN)-λ- and IFN-stimulated genes (ISGs). In...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Source Type: research