Human rhinovirus HRV16 induces antiviral responses and inhibits regeneration of human lung microvascular endothelium

Rhinoviral infections are the most common trigger of serious asthma exacerbations. It is not known if human rhinovirus (HRV16) may affect lung vascular endothelium. We investigated the effect of HRV16 on the antiviral and inflammatory responses in human lung endothelium, its barrier functions and regeneration. Human primary lung microvascular endothelial cells (HMVEC) were induced with HRV16 (MOI 0.1, 1 or 3) for 3 hours. Then cells were washed and cultured for following 72 hours. Virus copy number, interferons (IFNs), chemokines, innate immune receptors (TLR3, MDA5 and RIG-1), host antiviral enzymes (OAS-1 and PKR) mRNA expression (real-time pcr) and release (ELISA), apoptosis (flow cytometry), wound healing and migration (RTCA-DP) were assessed. In blocking experiments, anti-ICAM-1 antibodies were used. HRV16 infected and replicated in HMVEC (p<0.05). HRV16 increased IFN-beta, IFN-lambda, RANTES and IP-10 release (p<0.05) and innate immune receptors (TLR3, RIG-1, MDA-5) expression. HRV16 induced host antiviral resistance mechanisms by enhancing OAS-1 and PKR expression (p<0.05). ICAM-1 blockage diminished these effects (p<0.05). HRV16 decreased integrity of HMVEC, increased permeability (p<0.01) and induced their apoptosis (p<0.05). HRV16 slowed down the wound healing process (p<0.05) and migration (p<0.05) of HMVEC, which was accompanied by the decrease of regenerative and migratory agents (TGF-beta, periostin and IL-33) expression (p<0.05) Human rhinovirus may infect lung vascular endothelium and induce anti-viral and inflammatory responses. It may decrease barrier functions and regeneration of lung endothelium. Thus, lung vascular endothelium may become an important player in the modulation of immune responses during rhinoviral asthma exacerbations. NCN 2017/25/B/NZ5/01575