Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

Abstract

Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases.

Host Antiviral Response Suppresses Ciliogenesis and Motile Ciliary Functions in the Nasal Epithelium

“…Respiratory viral infections are implicated as drivers and exacerbators of chronic airway inflammatory diseases ( Tan et al, 2017 , 2020 ). Respiratory viruses such as respiratory syncytial virus (RSV) directly affect the ciliary architecture and function ( Smith et al, 2014 ), while influenza virus (IFV) and rhinovirus (RV) infections lead to the breakdown of the epithelial barrier ( Tan et al, 2020 ).…”

“…Respiratory viral infections are implicated as drivers and exacerbators of chronic airway inflammatory diseases ( Tan et al, 2017 , 2020 ). Respiratory viruses such as respiratory syncytial virus (RSV) directly affect the ciliary architecture and function ( Smith et al, 2014 ), while influenza virus (IFV) and rhinovirus (RV) infections lead to the breakdown of the epithelial barrier ( Tan et al, 2020 ). During such infections, the viruses first infect and damage the epithelial cells, where loss of the epithelial barrier occurs as a result of direct viral-induced cell death, or removal of infected cells by cell-mediated immune responses.…”

Recent Advances in Pathophysiology, Drug Development and Future Perspectives of SARS-CoV-2

“…SARS create holes in the lungs, which have a honeycomb appearance. This is probably due to an over-reactive immune response, which affects healthy and infected tissue and generates scars that stiffen the lungs ( Tan K.S. et al, 2020 ).…”

“…Severe SARS-CoV-2 infections are associated with lymphocytopenia, which is a severe loss of lymphocytes in the bloodstream. Many cytokines are released in SARS-CoV-2 patients and cause a cytokine storm such as IL-6, IL-1, IL-2, IL-10, TNF-α, and IFN-, Increased level of IL-6 in the serum leads ARDS and adverse clinical outcome, such as respiratory failure ( Tan K.S. et al, 2020 ; Tan L. et al, 2020 ).…”

Pulmonary Surfactants: a New Therapeutic Target in Asthma

“…However, surfactants enhance clearance of viruses via a carbohydrate recognition domain (CRD)–dependent manner [ 42 ••]. More recently, certain strains of coronavirus have also been revealed to be involved in asthma exacerbations [ 43 ]. A glycoprotein on coronavirus was specifically recognized by SP-D, but not by mannan-binding lectin [ 44 ].…”