Rhinoviral Infection of the Human Lung Vascular Endothelium May Protect From the Secondary Infection With Rhinovirus <scp>RV</scp>‐16

Rhinoviruses are a major cause of respiratory infections, including asthma infectious exacerbations. Human rhinovirus 16 (RV-16) has been widely shown to infect respiratory epithelial cells and the human lung vascular endothelium. RV-16 was also observed to induce an IFN-β-dependent mechanism of antiviral intracellular mechanisms based on OAS-1 and PKR activity. This study aimed to investigate whether the human lung microvascular endothelial cells (HMVEC-L) infected with RV-16 display a resistance to subsequent infections with the same virus, RV-16. HMVEC-L were infected with RV-16 and reinfected with RV-16 on Day 5. IFN-β-dependent responses, antiviral protein expression, inflammatory cytokine levels, and a viral copy numbers were assessed by real-time PCR, flow cytometry, ELISA, and confocal microscopy. RV-16 infection induced a significant IFN-β production and an activation of IFN-β-dependent antiviral proteins in HMVEC-L. On Day 5 post infection, these antiviral mechanisms remained active. In cells reinfected with RV-16, significantly lower replication of RV-16 was observed as compared to cells primarily infected with RV-16 on Day 5. Concomitantly, reinfected HMVEC-L showed a weaker response in IFN-β and inflammatory cytokine production. HMVEC-L infected with RV-16 display a sustained activation of IFN-β-dependent antiviral mechanisms, conferring resistance to subsequent infections with RV-16.