Pan‐Viral Screening of Respiratory Tract Infections in Adults With and Without Asthma Reveals Unexpected Human Coronavirus and Human Rhinovirus Diversity

Kistler, Amy; Avila, Pedro C.; Rouskin, Silvi; Wang, David; Ward, Theresa A.; Yagi, Shigeo; Schnurr, David P.; Ganem, Don; DeRisi, Joseph L.; Boushey, Homer A.

doi:10.1086/520816

Cited by 258 publications

(248 citation statements)

References 43 publications

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“…Data from these populations could be informative in defining the normal lung microbiota as well as the changes of microbial composition resulting in COPD onset. Second, besides bacteria, the importance of viruses and fungi in COPD is just beginning to be appreciated and studied [36][37][38]. A systems biology view of bacterial, viral and fungal microbiomes integrating additional host response factors such as host transcriptome and metabolome profiles would boost our understanding of the host-microbiota interaction and its implication in disease aetiology.…”

Section: Network Analysis Reveals Potential Microbiota Interactionsmentioning

confidence: 99%

Lung microbiome dynamics in COPD exacerbations

et al. 2016

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Increasing evidence suggests that the lung microbiome plays an important role in chronic obstructive pulmonary disease (COPD) severity. However, the dynamics of the lung microbiome during COPD exacerbations and its potential role in disease aetiology remain poorly understood.We completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on 476 sputum samples collected from 87 subjects with COPD at four visits defined as stable state, exacerbation, 2 weeks post-therapy and 6 weeks recovery.Our analysis revealed a dynamic lung microbiota where changes appeared to be associated with exacerbation events and indicative of specific exacerbation phenotypes. Antibiotic and steroid treatments appear to have differential effects on the lung microbiome. We depict a microbial interaction network for the lung microbiome and suggest that perturbation of a few bacterial operational taxonomic units, in particular Haemophilus spp., could greatly impact the overall microbial community structure. Furthermore, several serum and sputum biomarkers, in particular sputum interleukin-8, appear to be highly correlated with the structure and diversity of the microbiome.Our study furthers the understanding of lung microbiome dynamics in COPD patients and highlights its potential as a biomarker, and possibly a target, for future respiratory therapeutics. @ERSpublications Lung microbiome changes are associated with COPD exacerbation events and implicated in host inflammatory responses

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Section: Network Analysis Reveals Potential Microbiota Interactionsmentioning

confidence: 99%

Lung microbiome dynamics in COPD exacerbations

et al. 2016

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“…Data from studies using molecular diagnostics in the United States (52,53,62,64,79), Australia (74,75), Hong Kong (10), China (43), and Germany (95) demonstrate that there are at least 50 more HRV strains than had been previously appreciated. Analysis of full-genome sequences of these newly identified HRVs indicates that the majority belong to a unique species now designated HRV-C (86).…”

Section: Hrv-cmentioning

confidence: 99%

The ABCs of Rhinoviruses, Wheezing, and Asthma

Gern

2010

J Virol

230

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Human rhinoviruses (HRVs) were discovered as common cold pathogens over 50 years ago. Recent advances in molecular viral diagnostics have led to an appreciation of their role in more-significant respiratory illnesses, including bronchiolitis in infancy, childhood pneumonia, and acute exacerbations of chronic respiratory diseases such as asthma, chronic obstructive lung disease, and cystic fibrosis. Until a few years ago, only two groups of HRVs (A and B) had been recognized. However, full and partial sequencing of HRVs led to the discovery of a third species of HRV (HRV-C) that has distinct structural and biologic features. Risk factors and pathogenic mechanisms for more-severe HRV infections are being defined, and yet fundamental questions persist about mechanisms relating this common pathogen to allergic diseases and asthma. The close relationship between HRV infections and asthma suggests that antiviral treatments could have a major impact on the morbidity associated with this chronic respiratory disease.Virology and clinical textbooks and virtually all web-based information sources generally describe human rhinoviruses (HRVs) as the most frequent cause of the common cold. In this light, HRVs are important pathogens because common colds are so widespread and annoying, and from an economic perspective, supplying symptomatic-relief medications is a huge industry. A 2003 study estimated that expenditures on common cold medications in the United States exceeded 4 billion dollars, including 1.1 billion dollars spent on inappropriate prescriptions for antibiotics (18). Finding a cure for the common cold has been a much-publicized goal ever since HRVs were first discovered in the 1950s and 1960s. The basic biology of the replication cycle was soon described, and most HRVs were found to replicate best at 33°to 35°C (88, 99), which is consistent with their role as upper airway pathogens. HRVs were found to have tremendous diversity, and approximately 100 serotypes in two groups (A and B) had been identified by 1990, when it was presumed that all, or nearly all, HRVs had been identified. These HRVs were found to bind to one of two main receptors: ICAM-1 (major group) (30) and the low-density-lipoprotein receptor (most of the minor group) (35). Despite advances in understanding HRV genetics and the picornavirus replication cycle, efforts toward developing specific antivirals have fallen short due to modest efficacy, side effects, drug interactions, and economic considerations (16). Consequently, enthusiasm for pursuing a common cold cure has waned, and the pharmaceutical industry has refocused attention on viruses that cause more-significant illnesses. This failure is a bit embarrassing. As summarized by White and Fenner, "In this era of organ transplantation, genetic engineering, and other dramatic demonstrations of the wonders of medical science, the man in the street perceives a certain irony in the inability of modern medicine to make the slightest impact on that most trivial of all human ailments, the common cold" ...

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“…Rates of evolutionary change and the Time to the Most Recent Common Ancestor (TMRCA) of the novel clade were estimated by using the Bayesian Markov Chain Monte Carlo approach (BEAST package [14]; ), applying a relaxed molecular clock with an uncorrelated lognormal distribution of rates, a GTR + I + Γ 4 model of nucleotide substitution (determined by MODELTEST [15]), and exponential population growth. Statistical uncertainty in each parameter estimate is expressed as 95% highest probability density (HPD) values.…”

Section: The Studymentioning

confidence: 99%