A new and potentially more pathogenic group of human rhinovirus (HRV), group C (HRVC), has recently been discovered. We hypothesised that HRVC would be present in children with acute asthma and cause more severe attacks than other viruses or HRV groups.Children with acute asthma (n5128; age 2-16 yrs) were recruited on presentation to an emergency department. Asthma exacerbation severity was assessed, and respiratory viruses and HRV strains were identified in a nasal aspirate.The majority of the children studied had moderate-to-severe asthma (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC was present in the majority of children with acute asthma (59.4%) and associated with more severe asthma. Children with HRVC (n576) had higher asthma severity scores than children whose HRV infection was HRVA or HRVB only (n534; p50.018), and all other children (n550; p50.016). Of the 19 children with a non-HRV virus, 13 had HRV co-infections, seven of these being HRVC.HRVC accounts for the majority of asthma attacks in children presenting to hospital and causes more severe attacks than previously known HRV groups and other viruses.

Rationale: Human rhinoviruses (HRVs) consist of approximately 160 types that cause a wide range of clinical outcomes, including asymptomatic infections, common colds, and severe lower respiratory illnesses. Objectives: To identify factors that influence the severity of HRV illnesses. Methods: HRV species and types were determined in 1,445 nasal lavages that were prospectively collected from 209 infants participating in a birth cohort who had at least one HRV infection. Questionnaires were used during each illness to identify moderate to severe illnesses (MSI). Measurements and Main Results: Altogether, 670 HRV infections were identified, and 519 of them were solitary infections (only one HRV type). These 519 viruses belonged to 93 different types of three species: 49 A, 9 B, and 35 C types. HRV-A (odds ratio, 8.2) and HRV-C (odds ratio, 7.6) were more likely to cause MSI compared with HRV-B. In addition, HRV infections were 5-to 10-fold more likely to cause MSI in the winter months (P , 0.0001) compared with summer, in contrast to peak seasonal prevalence in spring and fall. When significant differences in host susceptibility to MSI (P ¼ 0.004) were considered, strain-specific rates of HRV MSI ranged from less than 1% to more than 20%. Conclusions: Factors related to HRV species and type, season, and host susceptibility determine the risk of more severe HRV illness in infancy. These findings suggest that anti-HRV strategies should focus on HRV-A and -C species and identify the need for additional studies to determine mechanisms for seasonal increases of HRV severity, independent of viral prevalence, in cold weather months.Keywords: rhinovirus; severe illness; species; type; seasonality Human rhinoviruses (HRVs) are the most prevalent human respiratory viruses. Annually, they infect billions of people and are responsible for at least one-half of all acute upper respiratory illnesses (common colds), the most common illness of humans (1-3). In addition to common colds, infections with HRV result in a wide range of other clinical outcomes ranging from asymptomatic infection to severe lower respiratory illnesses, such as bronchiolitis, pneumonia, and exacerbations of asthma (1, 4-7). It is likely that host, viral, and environmental factors contribute to the severity of illness caused by HRV infection. Indeed, more severe HRV infections are associated with phenotypic characteristics such as extremes in age; chronic respiratory diseases such as asthma; reduced interferon responses in the blood and airway; and, in early life, male sex and reduced lung function (4,8). Little is known about viral and environmental determinants of illness severity.HRVs are a large group of genetically diverse RNA viruses and are classified phylogenetically into three species (A, B, and C). The 100 classical serotypes are found within species A and B, and approximately 50 newly identified types are HRV-Cs (5, 9-15). This tremendous genetic diversity represents a major obstacle toward developing both antivirals and vaccines for HRV, and iden...

Background-Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity.

Human rhinoviruses (RVs), comprising three species (A, B, and C) of the genus Enterovirus, are responsible for the majority of upper respiratory tract infections and are associated with severe lower respiratory tract illnesses such as pneumonia and asthma exacerbations. High genetic diversity and continuous identification of new types necessitate regular updating of the diagnostic assays for the accurate and comprehensive detection of circulating RVs. Methods for molecular typing based on phylogenetic comparisons of a variable fragment in the 5= untranslated region were improved to increase assay sensitivity and to eliminate nonspecific amplification of human sequences, which are observed occasionally in clinical samples. A modified set of primers based on new sequence information and improved buffers and enzymes for seminested PCR assays provided higher specificity and sensitivity for virus detection. In addition, new diagnostic primers were designed for unequivocal species and type assignments for RV-C isolates, based on phylogenetic analysis of partial VP4/VP2 coding sequences. The improved assay was evaluated by typing RVs in >3,800 clinical samples. RVs were successfully detected and typed in 99% of the samples that were RV positive in multiplex diagnostic assays. Rhinoviruses (RVs) are members of the genus Enterovirus of the family Picornaviridae and are currently classified into three species (A, B, and C). More than 160 RV types have been identified to date, including 99 classic serotypes of RV-A and RV-B (1) and 6, 5, and 51 novel genotypes of RV-A, RV-B, and RV-C, respectively, classified genetically in the absence of serological cross-neutralization data (2-4). RVs are responsible for the majority of upper respiratory tract infections (common colds) and also can cause more severe illnesses of the lower respiratory tract, such as pneumonia and asthma exacerbations. The species affects the virulence, as RV-A and RV-C cause more severe illnesses in infants and are more likely to cause exacerbations of childhood asthma (5, 6).RV is a positive-sense single-stranded RNA virus with a genome of 7.1 to 7.2 kb, consisting of a single gene that codes for a long polyprotein of about 2,100 amino acids. The translated polyprotein is cleaved by viral proteases 2A and 3C to yield 11 mature proteins. The viral capsid is composed of 60 copies each of the VP4, VP2, VP3, and VP1 proteins. There are two untranslated regions (UTRs), i.e., the 5= UTR, which is typically 610 to 630 bases long and precedes the open reading frame, and the 3= UTR, which consists of 40 to 45 bases upstream of the poly(A) tract. The 5= and 3= UTRs contain a number of structural and sequence elements necessary for viral genome translation and replication. Sequence analyses of RVs reveal high genetic diversity, especially in the capsid-coding region, and evidence for recombination events mapped mainly in the 5= UTR and the protease 2A gene (7,8).Molecular methods for viral genome detection and sequencing directly in clinical samples are essential f...

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