The Role of Viruses in the Inception of Chronic Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a complex inflammatory disorder that affects between 2 and 16% of adults in the United States with estimated healthcare costs between 4 to 12 million USD. Viruses are a frequent cause of upper respiratory infections and a trigger for CRS exacerbations. There are several cross-sectional studies that have identified types of viruses associated with CRS. Rhinovirus, parainfluenza virus, influenza virus, and respiratory syncytial virus were the main associated viruses found in nasal lavage samples of patients with CRS. Other viruses such as adenovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have weak associations with CRS and were excluded from the review.Rhinovirus and its subtypes utilize glycoproteins like intercellular adhesion molecule 1 (ICAM-1), low density lipoprotein receptor (LDLR) family members, and cadherin-related family member 3 (CDHR3) to invade host cells. Influenza and parainfluenza virus invade through the binding of hemagglutinin (HA) to sialic acid-containing molecules while respiratory syncytial virus has a RSV specific glycoprotein that binds to the cellular receptor human nucleolin (NCL). Viral infection that causes CRS is frequently associated with type 1 and type 2 immune responses. Dysregulated immune response to viral infections can result in the activation of airway remodeling, epithelial-mesenchymal transitions, and epithelial barrier breakdown that are central to the pathogenesis of CRS. Risk factors for viral infections in CRS. Dysfunctional epithelial barrier function and age are strong risk factors for CRS infections. Comorbid respiratory diseases like asthma or allergic rhinitis are highly associated with CRS risk and CRS exacerbations. Children are also more likely to have upper respiratory tract infections than adults and viruses associated with CRS are more prevalent in infants and children. Studying and understanding the role of viruses in CRS is an important step in identifying disease pathogenesis and targeting these pathways early to slow disease progression.

SARS-CoV-2 and Other Respiratory Viruses in Human Olfactory Pathophysiology

“…Indeed, the PIV receptor CX3CR1 colocalizes to motile cilia is a plausible viral entry mechanism into the cells [62]. An additional study showed that the intercellular adhesion molecule-1 (ICAM-1) and related cytokine molecules is induced by PIV3 and it is thought that this activation participates in the inflammation during infection by viruses [63,64] (Figure 1A). Further research using the powerful of the transcriptomic analysis is necessary to help to delineate the role of PIV and implicated mechanisms in the development of the broad range of olfactory dysfunctions in patients and to find host-response transcript signature for possible treatments.…”

SARS-CoV-2 and Other Respiratory Viruses in Human Olfactory Pathophysiology

“…Indeed, the PIV receptor CX3CR1 colocalizes to motile cilia and is a plausible viral entry mechanism into the cells [ 55 ]. An additional study showed that the intercellular adhesion molecule-1 (ICAM-1) and related cytokine molecules are induced by PIV3, and it is thought that this activation participates in the inflammation during infection by viruses [ 56 , 57 ] ( Figure 1 ). Further research using the power of the transcriptomic analysis is necessary to help delineate the role of the PIV and implicated mechanisms in the development of the broad range of olfactory dysfunctions in patients and to find host-response transcript signatures for possible treatments.…”

“…As a PIV, the RSV targets the cilia of the epithelial cells in the airways by fusionning its F-glycoprotein to the cellular receptor human nucleolin (NCL). RSV also uses another mechanism that activates protein kinases like IGF1R to get into the cells [ 56 , 68 , 69 ]. Furthermore, recent studies have shown the essential role of the nucleolin RNA binding domain RBD1,2 in allowing the infection of RSV [ 70 ].…”

Epithelial Barrier in the Nasal Mucosa, Related Risk Factors and Diseases

“…Similar results were uncovered in AECs, where HRV infection decreased TJ expression at the epithelial barrier, reduced epithelial TER, and dissociated ZO-1 from TJ [ 187 , 188 , 189 ]. HRV can disrupt epithelial barrier function, and provide an environment for subsequent allergens to cross the epithelial cell layer and secondary responses [ 190 ].…”