Enterovirus (EV)71, which is closely related to RV, was also demonstrated to induce ER stress via activation PERK. non-enveloped viruses with an icosahedral capsid and a single-stranded positive-sense RNA (+ssRNA) genome made up of 7,200 bases (Palmenberg and Gern, 2015). So far, more than160 serotypes of RVs have Impulsin been discovered. They have been divided based on phylogeny into three species, Rhinovirus-A (RV-A), Rhinovirus-B (RV-B), and Rhinovirus-C (RV-C). Whereas RV-A and RV-B have smoother, spherical capsid structure, RV-C has 60 dominant spike-like protrusions, or fingers, on the outer surface of the virion (Liu et al., 2016). RV-C has a large deletion in VP1, one of the structural proteins, and it lacks a protruding plateau around each of the 5-fold vertices, a characteristic RAB25 feature of Impulsin RV-A and RV-B (Basta et al., 2014; Liu et al., 2016). RV-As include 80 serotypes, RV-Bs include 32 serotypes, and the recently found RV-C species contains at least 57 serotypes (http://www.picornaviridae.com). All three RV subgroups bind to plasma membrane glycoproteins to gain entry into the cells. Historically, RV-A and -B strains are classified into two groups depending on their cellular receptor utilization for internalization into the cells. Approximately 89 serotypes Impulsin Impulsin of RV-A and -B species belong to the major group and bind to human ICAM-1 (Greve et al., 1989); thus, showing the species specificity. The minor group RVs, which consist of at least 12 serotypes of RV-A, bind to the low-density lipoprotein receptor (LDLR) family with no species specificity. The receptor binding sites were mapped around the 5-fold axis of symmetry in viral capsid, but they have also shown to be different between the major and minor group RVs. The first domain of ICAM-1 binds the virus inside the canyon (a 2.5 nm depression) surrounding the dome at the vertex (Kolatkar et al., 1999). In contrast, the LDLR ligand-binding domain, composed of multiple ligand-binding repeats, attaches to the top of the star-like surface-exposed structure at the vertex (Hewat et al., 2000). These binding interactions are required for entry into the host cells by endocytosis. In addition to these receptors, RV-A and RV-B also interact with TLR2 on airway epithelial cells and macrophages, and this interaction modulates RV-induced innate immune responses (Unger et al., 2012; Ganesan et al., 2016; Bentley et al., 2019; Xander et al., 2019). Binding to TLR2 may not be necessary for viral entry into the host cells. More recently discovered RV-C binds to CDHR3, a member of the cadherin family of transmembrane proteins, which mediates RV-C entry into host cells. An asthma-related mutation (Cys529 Tyr) in CDHR3 is associated with increased viral binding and progeny yields and in subjects experiencing symptomatic colds (Sanders et al., 2001). NOS-2 generates nitric oxide, a potent antiviral agent. Human volunteers showed increase in nitric oxide generation in their nasal cavities after experimental infection with RV (Sanders et al., 2004). Exhaled nitric oxide correlated inversely with viral titer at 4 days post-RV infection in these volunteers. Later, nitric oxide was demonstrated to negatively regulate RV-induced CXCL-10 via NF-kB and IRF-1 downregulation (Spurrell et al., 2005; Koetzler et al., 2009; Zaheer et al., 2009); thus, implicating immunomodulatory role for nitric oxide in addition to antiviral property. Kaul et al. reported that replication-deficient RV induces reactive oxygen species via p47-phox while neutralization of reactive oxygen species reduced RV-stimulated IL-8 in these cells (Kaul et al., 2000). We demonstrated that RV transiently disrupts barrier function in polarized and mucociliary-differentiated airway epithelial cells and in a mouse model of RV infection (Sajjan et al., 2008). The disruption of barrier function was dependent on RV-induced.