Human Rhinovirus Species and Season of Infection Determine Illness Severity

Pediatrics, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin, United States.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 08/2012; 186(9). DOI: 10.1164/rccm.201202-0330OC
Source: PubMed


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. OBJECTIVE: To identify factors which influence the severity of HRV illnesses. METHODS: HRV species and types were determined in 1445 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 & 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 3 species: 49 A, 9 B and 35 C. HRV-A (OR 8.2 [2.7, 25]) and HRV-C (OR 7.6 [2.6, 23]) were more likely to cause MSI compared to HRV-B. In addition, HRV infections were 5-10-fold more likely to cause MSI in the winter months (p<0.0001) compared to summer, in contrast to peak seasonal prevalence in spring and fall. When significant differences in host susceptibility to MSI (p=0.004) were considered, strain-specific rates of HRV MSI ranged from <1% to over 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.

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Available from: Wai-Ming Lee
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    • "Virology have also been documented (Broberg et al., 2011; Fuji et al., 2011; Tapparel et al., 2011). However, strong evidence is lacking to definitely claim that HRV-Cs might be more virulent or more adapted to the lower airway environment (Iwane et al., 2011; Lee et al., 2012; Tapparel et al., 2011). "
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    ABSTRACT: New molecular diagnostic tools have recently allowed the discovery of human rhinovirus species C (HRV-C) that may be overrepresented in children with lower respiratory tract complications. Unlike HRV-A and HRV-B, HRV-C cannot be propagated in conventional immortalized cell lines and their biological properties have been difficult to study. Recent studies have described the successful amplification of HRV-C15, HRV-C11, and HRV-C41 in sinus mucosal organ cultures and in fully differentiated human airway epithelial cells. Consistent with these studies, we report that a panel of clinical HRV-C specimens including HRV-C2, HRV-C7, HRV-C12, HRV-C15, and HRV-C29 types were all capable of mediating productive infection in reconstituted 3D human primary upper airway epithelial tissues and that the virions enter and exit preferentially through the apical surface. Similar to HRV-A and HRV-B, our data support the acid sensitivity of HRV-C. We observed also that the optimum temperature requirement during HRV-C growth may be type-dependent.
    Full-text · Article · Nov 2013 · Virology
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    • "Sequence analysis of clinical HRV isolates have shed some light on the molecular epidemiology of the virus. Among pediatric populations , HRV species A and C have been associated with severe disease more frequently than species B [17] [18] [26] [27]. Investigation of a LTCH outbreak in the United States in 2003 with unusually high morbidity and mortality revealed a rhinovirus species A was responsible [6]. "
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    ABSTRACT: Human rhinoviruses (HRVs) are a well-recognized cause of long-term care home (LTCH) outbreaks of respiratory illness. However, there are limited data on the molecular epidemiology of the HRV types involved. To determine whether a large respiratory outbreak in a LTCH was caused by a single type of HRV, and to describe the clinical impact of the outbreak. Nasopharyngeal swabs were collected from residents with one or more of the following: fever, cough, rhinitis, or congestion. Specimens were interrogated by multiplex PCR using the ResPlex II assay. Samples positive for HRV were then submitted for genotyping by partial sequence analysis of the 5' untranslated (UTR) and viral protein (VP) 1 capsid regions. Of 71 screened, 56 residents were positive for a HRV during an outbreak that lasted 5.5 weeks; 27 healthcare workers also had respiratory symptoms. Three residents were transferred to hospital and 2 died. Seven units in two wings of the LTCH were affected, resulting in 3152.5 resident unit closure days. Three different HRV genotypes were identified, although HRV-A1 dominated. This large outbreak of HRVs among residents and healthcare workers in a LTCH was associated with substantial resident and staff morbidity as well as significant unit closures. Multiple types of HRV were implicated but an HRV-A1 type dominated, warranting further investigation into viral determinants for virulence and transmission.
    Full-text · Article · Jul 2013 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
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    • "There is some evidence that HRV-C may be more virulent than other species (Kaida et al., 2011; Mak et al., 2011). For example, HRV-C may be more likely than HRV-B to cause more severe illnesses in infancy (Lee et al., 2012), and HRV-C may be more likely than other species to cause acute exacerbations of asthma (Bizzintino et al., 2011; Fry et al., 2011). These findings, along with distinct genetic features and use of alternative cell surface receptor(s) (Bochkov et al., 2011), suggest that there may be important differences in the replication cycle of HRV-C viruses compared to other HRV. "
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    ABSTRACT: Information about the basic biological properties of human rhinovirus-C (HRV-C) viruses is lacking due to difficulties with culturing these viruses. Our objective was to develop a cell culture system to grow HRV-C. Epithelial cells from human sinuses (HSEC) were differentiated at air-liquid interface (ALI). Differentiated cultures supported 1-2logs growth of HRV-C15 as detected by quantitative RT-PCR. Two distinguishing features of HRVs are acid lability and optimal growth at 33-34°C. We used this system to show that HRV-C15 is neutralized by low pH (4.5). In contrast to most HRV types, replication of HRV-C15 and HRV-C41 was similar at 34 and 37°C. The HSEC ALI provides a useful tool for quantitative studies of HRV-C replication. The ability of HRV-C to grow equally well at 34°C and 37°C may contribute to the propensity for HRV-C to cause lower airway illnesses in infants and children with asthma.
    Full-text · Article · Nov 2012 · Virology
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