Rhinovirus: A Narrative Review on Its Genetic Characteristics, Pediatric Clinical Presentations, and Pathogenesis

Abstract

Human rhinoviruses (HRVs) are the leading cause of common colds. With the development of new molecular methods since the 2000s, HRVs have been increasingly involved among severe clinical infections. Recent knowledge of the HRV genetic characteristics has also improved the understanding of their pathogenesis. This narrative review aims to provide a current comprehensive knowledge about this virus in the pediatric community. HRVs represent a main cause of upper and lower respiratory tract infections in children. HRV is the second virus involved in bronchiolitis and pneumonia in children, and HRV bronchiolitis has a higher risk of recurrent wheezing episode or asthma. Some recent findings described HRVs in stools, blood, or cerebrospinal fluid, thanks to new molecular techniques such as polymerase chain reaction (PCR) by detecting HRVs with high sensibility. However, the high rate of asymptomatic carriage and the prolonged excretion in postsymptomatic patients complicate interpretation. No sufficient data exist to avoid antibiotic therapy in pediatric high-risk population with HRV detection. Severe clinical presentations due to HRVs can be more frequent in specific population with chronic pathology or genetic particularity. Inflammatory response is mediated by the nuclear factor (NF)-kappa B pathway and production of interferon (IFN)-beta and IFN-gamma, interleukin 8 (IL8), and IL1b. No specific treatment or antiviral therapy exists, although research is still ongoing. Nowadays, in addition to benign diseases, HRVs are recognized to be involved in some severe clinical presentations. Recent advances in genetic knowledge or specific inflammatory response may lead to specific treatment.

Keywords: children; enterovirus; respiratory tract infection; respiratory virus; rhinovirus.

Figure 1

Phylogenetic tree of human rhinoviruses obtained by comparison of near full-length genome using approximated maximum of likelihood with FastTree2.1.

Figure 2

Human rhinoviruse (HRV) replication and inflammatory response. Depending on the serotype, HRVs use intercellular adhesion molecule 1 (ICAM-1), cadherin-related family 3 (CDHR3), or low-density lipoprotein receptor (LDL-R) for endocytosis. After binding, HRV upregulates ICAM-1 and other receptors expression (34). A pH drop leads to viral uncoating after the loss of the capsid protein VP4 and externalization of hydrophobic N-terminal of VP1 (36). In the endosome, viral RNAs are recognized by Toll-like receptor 3 (TLR3) and TLR7/8, while receptors are recycled to apical plasma membrane (37). Nuclear factor (NF)-kappa B pathway and the pattern recognition receptors ([RIG-1] and [MDA-5]) in the intracellular compartment are activated, leading to the production of interleukin 8 (IL8), IL1b, IL6, IL12, and interferon (IFN) beta and gamma. The cascade leads in fine to the increased production of T cells and neutrophil cytokines.