Human Rhinovirus Diversity and Evolution: How Strange the Change from Major to Minor

Abstract

Rhinoviruses are the most common causes of the common cold. Their many distinct lineages fall into "major" and "minor" groups that use different cell surface receptors to enter host cells. Minor-group rhinoviruses are more immunogenic in laboratory studies, although their patterns of transmission and their cold symptoms are broadly similar to those of the major group. Here we present evolutionary evidence that minor-group viruses are also more immunogenic in humans. A key finding is that rates of amino acid substitutions at exposed sites in the capsid proteins VP2, VP3, and VP1 tend to be elevated in minor-group relative to majorgroup viruses, while rates at buried sites show no consistent differences. A reanalysis of historical virus watch data also indicates a higher immunogenicity of minor-group viruses, consistent with our findings about evolutionary rates at amino acid positions most directly exposed to immune surveillance. The increased immunogenicity and speed of evolution in minor-group lineages may contribute to the very large numbers of rhinovirus serotypes that coexist while differing in virulence.IMPORTANCE Most colds are caused by rhinoviruses (RVs). Those caused by a subset known as the minor-group members of rhinovirus species A (RV-A) are correlated with the inception and aggravation of asthma in at-risk populations. Genetically, minor-group viruses are similar to major-group RV-A, from which they were derived, although they tend to elicit stronger immune responses. Differences in their rates and patterns of molecular evolution should be highly relevant to their epidemiology. All RV-A strains show high rates of amino acid substitutions in the capsid proteins at exposed sites not previously identified as being immunogenic, and this increase is significantly greater in minor-group viruses. These findings will inform future studies of the recently discovered RV-C, which also appears to exacerbate asthma in adults and children. In addition, these findings draw attention to the difficult problem of explaining the long-term coexistence of many serotypes of major-and minor-group RVs.KEYWORDS human rhinovirus, immunogenicity, major-group rhinoviruses, minor-group rhinoviruses, molecular evolution C old infections are caused by more than 250 virus serotypes belonging to at least five different families. The most common cold-causing viruses are rhinoviruses (RVs) (10 to 50% of all colds), coronaviruses (10 to 15% of all colds), and influenza viruses (5 to 15% of all colds) (1, 2). Globally, RVs are the primary cause of acute upper respiratory tract infections. Although most such infections are mild, RVs can also replicate in the lower respiratory tract and exacerbate the severity of conditions such as chronic respiratory disease and asthma (3-7).Rhinoviruses are nonenveloped, positive-sense, single-stranded RNA viruses belonging to the genus Enterovirus of the family Picornaviridae that infect epithelial cells that

Rhinovirus and preschool wheeze

“…Rhinovirus belonging to the minor group (12 serotypes of RV‐A using the LDL‐receptor) has been shown to be more immunogenic than RV belonging to the major group (both RV‐A and RV‐B using the ICAM‐1 receptor) . Schuler et al .…”

“…Rhinovirus belonging to the minor group (12 serotypes of RV-A using the LDL-receptor) has been shown to be more immunogenic than RV belonging to the major group (both RV-A and RV-B using the ICAM-1 receptor). 59 Schuler et al 33 report that RV infections caused by minor and major RV serotypes cause dissimilar inflammatory response such as different cytokine release, transcription factor phosphorylation, and activation from macrophages, suggesting that the receptor plays an important role in creating the inflammatory response in the human airway upon exposure to RV. 33…”

Cryo-EM structure of rhinovirus C15a bound to its cadherin-related protein 3 receptor

“…Site Commonalities with Other RV-C. Among the RV-A and RV-B genotypes that use ICAM-1 and LDLR, there is significant sequence latitude in the virus surface footprints contributing to receptor interactions (1,36,37). Soluble CDHR3 EC1, when incubated with virus before cell attachment, is a potent inhibitor of replication for at least four determined RV-C genotypes (24).…”

Elucidating the Interaction of CF Airway Epithelial Cells and Rhinovirus: Using the Host-Pathogen Relationship to Identify Future Therapeutic Strategies

“…The external capsid proteins comprise of VP1, VP2, VP3, while VP4 is located between the interface of capsid protein and RNA genome. These capsid proteins feature a high degree of heterogeneity and consequently the significant antigenic diversity among RV has precluded vaccine development (Glanville and Johnston, 2015 ; Lewis-Rogers et al, 2017 ). Currently, there are more than 150 serotypes of RV, which have been classified into 3 species; RV-A, RV-B, and RV-C.…”