Rhinovirus elicits proasthmatic changes in airway responsiveness independently of viral infection

Background: Rhinovirus (RV), the principal pathogen responsible for the common cold, is importantly implicated in triggering attacks of asthma secondary to changes in airway responsiveness. Objective: Because the airway histopathologic features of RV infection are relatively modest, we tested the hypothesis that RV can directly elicit proasthmatic-like changes in airway smooth muscle (ASM) responsiveness independently of actual viral infection and its associated cytopathic effects. Methods: Isolated ASM tissues and cultured ASM cells were inoculated with either infectious or noninfectious (UV-Irradiated) RV16 and RV2, the latter serotypes belonging to the "major" and "minor" groups of RV subtypes, respectively. ASM constrictor and relaxant responsiveness, G(i) protein expression, and proinflammatory cytokine release were subsequently compared under the different treatment conditions. Results: In contrast to RV2, which had no effect, RV16 inoculation elicited enhanced ASM contractility and impaired relaxation to cholinergic and beta -adrenergic agonists, respectively, in association with increased ASM membrane G(i) protein expression and induced release of the proinflammatory cytokines IL-5 and IL-1 beta. These proasthmatic-like effects were also observed in ASM exposed to UV-irradiated RV16, wherein viral replication was completely inhibited. In contrast, pretreatment of ASM with a neutralizing antibody directed against ICAM-1, the host receptor for the "major" group of RVs, completely abrogated the proasthmatic effects of RV16. Conclusions: The results demonstrate that (1) RV16 elicits proasthmatic changes in ASM responsiveness that can occur independently of actual viral infection of the ASM and (2) the effects of RV16 are attributed solely to binding of the virus to its host receptor (ICAM-1) on the ASM cell surface. Collectively, these findings support the notion that RV-induced exacerbation of wheezing in asthmatic individuals can occur even in the absence of any cytopathology associated with viral infection.