Hydroxychloroquine (HCQ) inhibits rhinovirus (RV) replication in cultured human tracheal epithelial cells

Abstract

Rationale The immunomodulating agent, HCQ, inhibits transmission of respiratory viruses adenovirus and influenza, which require acidified cytoplasmic vesicles for cellular entry. Based on an apparent low incidence of symptomatic upper respiratory tract infections in asthmatics treated with oral HCQ, we hypothesized that HCQ might inhibit RV infection in respiratory epithelial cells. Methods Differentiated cultures of human tracheal epithelial cells grown at an air liquid interface were pre-incubated for 12h with 50 μM HCQ prior to 12h infection with RV serotype 16. Twelve hours after removal of virus, numbers of infected cells were measured using confocal Immunofluorescence microscopy. Levels of mRNA for RV were quantified using multiplex two-step RT-PCR. Release of IL-8 was measured by ELISA. Results Small numbers of cells positive for RV-16 in control cultures were significantly increased by RV-16 infection, an effect substantially blocked by HCQ (see Table). Furthermore, HCQ reduced levels of viral mRNA in infected cells by 32-fold. Viral infection was also associated with increased output of IL-8 into both apical and basolateral media, and again HCQ inhibited this (see Table). ∗ Condition % Infected Cells IL-8 production (pg.cm −3.h −1) Control 0.12 ± 0.1 203 ± 26 RV16 4.36 ± 0.94 96 ± 37 RV16 + HCQ 1.01 ± 0.21 ∗ 339 ± 46 ∗ ∗ Significantly less than with virus alone. Conclusions These findings demonstrate potent in vitro inhibition of RV infection by HCQ and suggest that targeted topical delivery of HCQ to the respiratory epithelium may offer a novel strategy for prevention of RV infections.