Rhinoviruses and Their Receptors: Implications for Allergic Disease

Abstract

Human rhinoviruses (RVs) are picornaviruses that can cause a variety of illnesses including the common cold, lower respiratory tract illnesses such as bronchitis and pneumonia, and exacerbations of asthma. RVs are classified into three species, RV-A, B, and C, which include over 160 types. They utilize three major types of cellular membrane glycoproteins to gain entry into the host cell: intercellular adhesion molecule 1 (ICAM-1) (the majority of RV-A and all RV-B), low-density lipoprotein receptor (LDLR) family members (12 RV-A types), and cadherin-related family member 3 (CDHR3) (RV-C). CDHR3 is a member of cadherin superfamily of transmembrane proteins with yet unknown biological function, and there is relatively little information available about the mechanisms of RV-C interaction with CDHR3. A coding single nucleotide polymorphism (rs6967330) in CDHR3 could promote RV-C infections and illnesses in infancy, which could in turn adversely affect the developing lung to increase the risk of asthma. Further studies are needed to determine how RV infections contribute to pathogenesis of asthma and to develop the optimal treatment approach to control asthma exacerbations.

Keywords: Allergy; Asthma; CDHR3; Cellular receptor; Human rhinovirus; ICAM-1; LDLR.

Fig.1

Potential mechanisms of RV-C infection in normal and asthmatic airway epithelium. We speculate, based on function of other cadherins, that CDHR3 could be preferentially localized on the cell surface within intercellular junctions. The CDHR3 genotype (rs6967330) that converts amino acid residue cysteine to tyrosine at position 529 (C₅₂₉→Y) leads to an increased cell surface expression of CDHR3. a. In a healthy intact epithelium with normal barrier function, CDHR3 is likely to be less accessible for RV-C binding resulting in a reduced infection and mild illness. b. Chronic allergic inflammation in asthmatic airways reduces epithelial barrier function, and this could secondarily increase accessibility of CDHR3 for RV-C binding in individuals with “asthma risk” genotype. As a result, RV-C could infect more cells, leading to more severe respiratory illness. Eos, eosinophils; ILC2, type 2 innate lymphoid cell.