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Vascular endothelium is a semi-permeable barrier that regulates the flow of nutrients, ions, cytokines and immune cells between blood and tissues. Barrier properties of endothelium, its ability to regenerate and the potential for secretion of inflammatory mediators play a crucial role in maintaining local tissue homeostasis. The lung vascular endothelial cells were shown to be infected by human rhinovirus (HRV) and generate antiviral, inflammatory and cytopathic responses. The current study reveals that in the long-time manner, the lung vascular endothelium may efficiently limit the HRV replication via the IFN-dependent 2'-5'-oligoadenylate synthetase 1 activation. This leads to the restoration of integrity accompanied by the up-regulation of adherens and tight junctions, increase of metabolic activity and proliferation rate. Secondly, HRV16-infected cells show delayed and transient up-regulation of the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor, angiopoietin 1 and 2, and neuropilin-1, as well as VEGF receptors. The lung vascular endothelium infected with HRV may limit the infection, recover in time, and regain barrier properties and metabolic functions, thus leading to the restoration of integrated barrier tissue., (© 2022 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

The effect of rhinovirus on airway epithelium is very well described. However, its influence on the vascular endothelium is unknown. The current study assesses the effect of rhinovirus HRV16 on the antiviral and inflammatory response in the human vascular endothelial cells (ECs). HRV16 increased IFN-β, RANTES, and IP-10 mRNA expression and protein release. HRV16 copy number in ECs reached maximal value 10 h after incubation. Increase in virus copies was accompanied by the enhancement of Toll- and RIG-I-like receptors: TLR3, RIG-I, and MDA5. Additionally, HRV16 increased OAS-1 and PKR mRNA expression, enzymes responsible for virus degradation and inhibition of replication. ICAM-1 blockade decreased HRV16 copy number in ECs and inhibited IFN-β, RANTES, IP-10, OAS1, PKR, TLR3, RIG-I, and MDA5 mRNA expression increase upon subsequent induction with HRV16. The vascular endothelium may be infected by human rhinovirus and generate antiviral and inflammatory innate response. Results of the study indicate the possible involvement of the vascular endothelium in the immunopathology of rhinoviral airway infections., (© 2020 APMIS. Published by John Wiley & Sons Ltd.)

Human rhinovirus 16 (HRV16) may induce inflammatory and antiviral responses in the human lung vascular endothelium (ECs) and impair its barrier functions after infection. However, ECs may regain barrier and metabolic functions. Mechanisms of limitation of HRV16 infection in the lung vascular endothelium are unknown. Human lung vascular endothelium (HMVEC-L) was infected with HRV16. IFN-β, OAS-1, and PKR expression was assessed by real-time PCR, flow cytometry, and confocal microscope. To prove the significance of IFN-β in the limitation of HRV16 replication, HMVEC-Ls were preincubated with anti-IFN-β Abs. To prove the involvement of OAS-1 and PKR in the IFNdependent limitation of HRV16 replication, HMVEC-Ls were transfected with respective siRNA. HRV16 stimulated IFN-β production and activated intracellular mechanisms of antiviral immunity based on OAS-1 and PKR activation. Blocking of IFN-β contributed to the inhibition of intracellular mechanisms of antiviral immunity (OAS-1, PKR) and boosted replication of HRV16. Effective OAS-1 silencing by siRNA caused the increase of HRV16 copy numbers after HRV16 infection. siRNA upregulated the other genes related to the antiviral response. The infected lung vascular endothelium may limit the HRV16 infection. This limitation may be associated with the induction of IFN-β-dependent intracellular mechanisms based on OAS-1 and PKR activity. [ABSTRACT FROM AUTHOR]