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

ABSTRACT 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.