A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants

Lee, Wai-Ming; Kiesner, Christin; Pappas, T.E.; Lee, Iris; Grindle, Kristine A.; Jartti, Tuomas; Jakieła, Bogdan; Lemanske, Robert F.; Shult, Peter; Gern, James E.

doi:10.1371/journal.pone.0000966

Cited by 287 publications

(356 citation statements)

References 57 publications

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“…20 PCR was performed by using 12.5 mL REDTaqReadyMix (SigmaAldrich), 200 nM of forward and reverse primer, 3 mL of cDNA template, and nuclease-free water. PCR products were cloned by using a TOPO TA cloning kit (Invitrogen, Carlsbad, CA).…”

Section: Molecular Virological Studiesmentioning

confidence: 99%

Duration of Rhinovirus Shedding in the Upper Respiratory Tract in the First Year of Life

Loeffelholz¹,

Trujillo

Pyles

et al. 2014

Pediatrics

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WHAT'S KNOWN ON THIS SUBJECT: Rhinoviruses are commonly detected in both acutely ill and asymptomatic infants and children. The finding may represent new infection or prolonged presence of rhinovirus RNA in the respiratory tract. WHAT THIS STUDY ADDS:In young, otherwise healthy infants, shedding of RNA from the same rhinovirus strain rarely persisted longer than 30 days. abstract BACKGROUND: Current molecular diagnostic methods have detected rhinovirus RNA in a high proportion of asymptomatic infants and children, raising the question of the clinical significance of these findings. This study investigates the prevalence of prolonged rhinovirus RNA presence in the upper respiratory tract of infants during the first year of life. METHODS:In a longitudinal study, infants were followed from birth up to 12 months. Nasopharyngeal specimens were collected monthly (months 1-6 and month 9) and during an upper respiratory infection. Rhinoviruses were detected by quantitative reverse-transcription polymerase chain reaction. Presence of repeated rhinovirus RNA was evaluated by nucleotide sequence analysis. RESULTS:A total of 2153 specimens from 362 infants were studied; 341 distinct rhinovirus infections in 216 infants were identified. Follow-up specimens were available within 30 days for 179 infections, creating the sample set to assess prolonged rhinovirus presence. Of the 179 infections, 46 involved the detection of the same rhinovirus strain in repeated specimens, including 8 events of prolonged presence of the same strain (detected in specimens collected .30 days apart), representing 4.5% of the evaluable rhinovirus infections. There were 26 events in which a rhinovirus strain was replaced by a different strain within a 30-day interval, representing 14.5% of the 179 infections. CONCLUSIONS:Although rhinovirus infections are common in healthy infants, prolonged presence of rhinovirus RNA in the respiratory tract after an upper respiratory infection was uncommon (,5%). Detection of rhinovirus RNA in an infant most likely represents an infection within a 30-day period. Dr Loeffelholz co-conceptualized and co-designed the study and wrote the initial manuscript; Dr Trujillo coordinated data collection; Dr Pyles conceptualized and supervised molecular virology studies and reviewed and revised the manuscript; Mr Miller performed molecular virology studies and provided interpretation of the data for inclusion in the manuscript; Dr Alvarez-Fernandez supervised data collection; Dr Pong performed molecular virology studies and performed data collection and analysis; Dr Chonmaitree conceptualized and designed the study, provided overall study supervision, and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. 4,5 A study in adult volunteers showed that cultivatable rhinoviruses were routinely recovered for ∼2 weeks after infection. 6 Recurrent rhinovirus infection has been described in patients with asthma 7 and in those at risk of developing...

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Section: Molecular Virological Studiesmentioning

confidence: 99%

Duration of Rhinovirus Shedding in the Upper Respiratory Tract in the First Year of Life

Loeffelholz¹,

Trujillo

Pyles

et al. 2014

Pediatrics

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“…These samples were analyzed for common respiratory viruses by multiplex polymerase chain reaction (respiratory MultiCode assay; EraGen Biosciences, Madison, WI) (12) and by seminested polymerase chain reaction specific for the hemagglutinin gene of the 2009 H1N1 influenza virus (see the online supplement for details). Partial genetic sequencing was used to identify HRV types (13).…”

Section: Procedures and Definitionsmentioning

confidence: 99%

Increased H1N1 Infection Rate in Children with Asthma

Kloepfer¹,

Olenec²,

Lee³

et al. 2012

Am J Respir Crit Care Med

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Rationale: The 2009 H1N1 flu appeared to cause more severe cold symptoms during the 2009-2010 flu season. Objectives: We evaluated H1N1 infections during peak viral season in children with and without asthma to determine whether the H1N1 infectivity rate and illness severity were greater in subjects with asthma. Methods: One hundred and eighty children, 4-12 years of age, provided eight consecutive weekly nasal mucus samples from September 5 through October 24, 2009, and scored cold and asthma symptoms daily. Viral diagnostics were performed for all nasal samples. Measurements and Main Results: One hundred and sixty-one children (95 with asthma, 66 without asthma) completed at least 6 of the 8 nasal samples. The incidence of H1N1 infection was significantly higher in children with asthma (41%) than in children without asthma (24%; odds ratio, 4; 95% confidence interval, 1.8-9; P , 0.001), but rates of human rhinovirus infection (90% each) and other viral infections (47 vs. 41%) were similar. In children with asthma, there was a nonsignificant trend for increased loss of asthma control during H1N1 infections compared with human rhinovirus infections (38 vs. 21%; odds ratio, 2.6; 95% confidence interval, 0.9-7.2; P ¼ 0.07). Conclusions: During peak 2009 H1N1 flu season, children with asthma were infected almost twice as often with H1N1 compared with other respiratory viruses. H1N1 infection also caused increased severity of cold symptoms compared with other viral infections. Given the increased susceptibility of children with asthma to infection, these findings reinforce the need for yearly influenza vaccination to prevent infection, and raise new questions about the mechanism for enhanced susceptibility to influenza infection in asthma.Keywords: asthma; viral infection; influenza 2009 H1N1 Flu was first reported in the United States in the spring of 2009, and eventually affected 61 million people (1), one-third of them children. Morbidity was high, with 87,000 children requiring hospitalization. The most common comorbidity for patients hospitalized as a result of H1N1 infection was asthma (2), and the percentage of children with asthma hospitalized because of the 2009 H1N1 virus was two-to fivefold higher than previous reports of hospitalization due to seasonal influenza (3, 4). Despite the observation that subjects with asthma suffer H1N1 illness with increased severity, it remains unclear at what rate they are infected and whether their symptom severity is greater than those of their nonasthmatic counterparts. Previous studies of H1N1 infectivity reflect symptomatic infections with limited reporting of mild or asymptomatic infection (5-7).A study by our group demonstrated that 90% of children with asthma are infected with human rhinoviruses (HRVs) during the month of September, and that the severity of clinical illness varies from no symptoms to severe wheezing illnesses (8). This study provided the foundation on which we designed a larger cohort to prospectively examine the relationship between illness symptom...

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“…One HRV strain originally assigned as HRV87 belongs to the enterovirus species HEV-D (Blomqvist et al, 2002;Ishiko et al, 2002;Oberste et al, 2004). Recent studies, which have applied direct RT-PCR and sequencing to clinical specimens, have discovered a third genetic clade that is distinct from HRV-A and HRV-B and is preliminarily called HRV-C (Arden et al, 2006;Kistler et al, 2007a; Lamson et al, 2006;Lau et al, 2007;Lee et al, 2007;McErlean et al, 2007; Savolainen-Kopra et al., 2009). HRVs are composed of an icosahedral protein capsid composed of 60 copies of protomers, each of which comprise a single molecule of four capsid proteins VP1-VP4, VP1 being the most exposed.…”

mentioning

confidence: 99%

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

Blomqvist

Savolainen-Kopra

Paananen

et al. 2009

Journal of General Virology

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Human rhinoviruses (HRVs), which are the most frequent causative agents of acute upper respiratory tract infections, are abundant worldwide. We have identified HRV strains in environmental specimens collected in Finland, Latvia and Slovakia during the surveillance of polioand other enteroviruses. These acid-sensitive HRV strains were isolated under conditions optimized for growth of most of the enteroviruses, i.e. in stationary human rhabdomyosarcoma cells incubated at 36 6C. Phylogenetic analysis of the sequences derived from the partial 59 noncoding region and the capsid region coding for proteins VP4/VP2 and VP1 showed that the HRV field strains clustered together with prototype strains of the HRV minor receptor group. Partial sequences of the 3D polymerase coding region generally followed this pattern, with the exception of a set of three HRV field strains that formed a subcluster not close to any of the established HRV-A types, suggesting that recombination may have occurred during evolution of these HRV strains. Phylogenetic analysis of the VP4/VP2 capsid protein coding region showed that the 'environmental' HRV field strains were practically identical to HRV strains recently sequenced by others in Australia, the United States and Japan. Analysis of amino acids corresponding to the intercellular adhesion molecule-1 receptor footprint in major receptor group HRVs and also in the low-density lipoprotein receptor footprint of minor receptor group HRVs showed conservation of the 'minor receptor group-like' amino acids, indicating that the field strains may have maintained their minor receptor group specificity. INTRODUCTIONHuman rhinoviruses (HRVs) belong to the family Picornaviridae and together with human enteroviruses (HEV) and a number of non-human enterovirus strains comprise the largest genus (Enterovirus) in the family (Knowles, 2008). Clinical illnesses caused by HRV are typically mild and self-limiting upper respiratory tract infections or common colds, but HRVs have also been increasingly associated with other clinical consequences of respiratory tract infection such as acute otitis media (NoksoKoivisto et al., 2004;Pitkaranta et al., 1998;Vesa et al., 2001), acute community-acquired sinusitis (Pitkaranta et al., 1997(Pitkaranta et al., , 2001), bronchiolitis (Hayden, 2004), pneumonia (Papadopoulos, 2004 and exacerbations of existing respiratory disorders such as asthma (Gern, 2002) and chronic obstructive pulmonary disease (Greenberg, 2002).HRV encompasses 100 designated serotypes, including two antigenically distinct subtypes of serotype HRV1 (HRV1A and HRV1B) (Hamparian et al., 1987;Kapikian et al., 1967Kapikian et al., , 1971. The current taxonomy is based on genetic relationships of HRV. Genetic analysis of VP4/VP2 (Savolainen et al., 2002a) and VP1 (Laine et al., 2005; Ledford et al., 2004) capsid protein coding regions showed that the 100 serotypes cluster into two genetically distinct species, HRV-A and HRV-B. One HRV strain originally assigned as HRV87 belongs to the enterovirus species H...

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A Diverse Group of Previously Unrecognized Human Rhinoviruses Are Common Causes of Respiratory Illnesses in Infants

Cited by 287 publications

References 57 publications

Duration of Rhinovirus Shedding in the Upper Respiratory Tract in the First Year of Life

Duration of Rhinovirus Shedding in the Upper Respiratory Tract in the First Year of Life

Increased H1N1 Infection Rate in Children with Asthma

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

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