Clinical and molecular features of human rhinovirus C

Department of Pediatrics, University of Wisconsin, School of Medicine and Public Health, Madison, WI 53792, USA.
Microbes and Infection (Impact Factor: 2.86). 01/2012; 14(6):485-94. DOI: 10.1016/j.micinf.2011.12.011
Source: PubMed


A newly discovered group of human rhinoviruses (HRVs) has been classified as the HRV-C species based on distinct genomic features. HRV-Cs circulate worldwide, and are important causes of upper and lower respiratory illnesses. Methods to culture and produce these viruses have recently been developed, and should enable identification of unique features of HRV-C replication and biology.

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    • "We and others have previously shown that development of persistent atopic (allergic) wheeze in children is linked to the number of virus-associated febrile and/or wheezy LRIs experienced during infancy (Jackson et al., 2008; Kusel et al., 2007, 2012; Oddy et al., 2002). The principal virus type of current interest is human rhinoviruses (HRVs), particularly subtype C (HRV-C) (Bochkov and Gern, 2012); however , respiratory syncytial virus (RSV) is also recognized as a major cause of infant LRI (Wu and Hartert, 2011). The relative contributions of these viral pathogens in asthma initiation remain controversial (Stein and Martinez, 2010). "
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    ABSTRACT: The nasopharynx (NP) is a reservoir for microbes associated with acute respiratory infections (ARIs). Lung inflammation resulting from ARIs during infancy is linked to asthma development. We examined the NP microbiome during the critical first year of life in a prospective cohort of 234 children, capturing both the viral and bacterial communities and documenting all incidents of ARIs. Most infants were initially colonized with Staphylococcus or Corynebacterium before stable colonization with Alloiococcus or Moraxella. Transient incursions of Streptococcus, Moraxella, or Haemophilus marked virus-associated ARIs. Our data identify the NP microbiome as a determinant for infection spread to the lower airways, severity of accompanying inflammatory symptoms, and risk for future asthma development. Early asymptomatic colonization with Streptococcus was a strong asthma predictor, and antibiotic usage disrupted asymptomatic colonization patterns. In the absence of effective anti-viral therapies, targeting pathogenic bacteria within the NP microbiome could represent a prophylactic approach to asthma. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Apr 2015 · Cell host & microbe
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    • "Among the HRV-A and HRV-B viruses, major-group HRV binds the intercellular adhesion molecule 1 (ICAM-1) receptor [7], whereas minor-group HRV binds the low-density lipoprotein receptor (LDL-R) [8], [9]. HRV-C viruses bind an as yet unknown receptor [10]. "
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    ABSTRACT: Major- and minor-group human rhinoviruses (HRV) enter their host by binding to the cell surface molecules ICAM-1 and LDL-R, respectively, which are present on both macrophages and epithelial cells. Although epithelial cells are the primary site of productive HRV infection, previous studies have implicated macrophages in establishing the cytokine dysregulation that occurs during rhinovirus-induced asthma exacerbations. Analysis of the transcriptome of primary human macrophages exposed to major- and minor-group HRV demonstrated differential gene expression. Alterations in gene expression were traced to differential mitochondrial activity and signaling pathway activation between two rhinovirus serotypes, HRV16 (major-group) and HRV1A (minor-group), upon initial HRV binding. Variances in phosphorylation of kinases (p38, JNK, ERK5) and transcription factors (ATF-2, CREB, CEBP-alpha) were observed between the major- and minor-group HRV treatments. Differential activation of signaling pathways led to changes in the production of the asthma-relevant cytokines CCL20, CCL2, and IL-10. This is the first report of genetically similar viruses eliciting dissimilar cytokine release, transcription factor phosphorylation, and MAPK activation from macrophages, suggesting that receptor use is a mechanism for establishing the inflammatory microenvironment in the human airway upon exposure to rhinovirus.
    Full-text · Article · Apr 2014 · PLoS ONE
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    • "Common to the original RV-A (74 serotypes) and RV-B (25 serotypes) is the use of ICAM-1 or LDLR for cell attachment and entry (Vlasak et al., 2005). They are labile at low pH (o5), and grow predominantly in sinus and upper airway tissues (for reviews, see (Bochkov and Gern, 2012; Ashraf et al., 2013)). "
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    ABSTRACT: Human rhinoviruses of the RV-C species are recently discovered pathogens with greater clinical significance than isolates in the RV-A+B species. The RV-C cannot be propagated in typical culture systems; so much of the virology is necessarily derivative, relying on comparative genomics, relative to the better studied RV-A+B. We developed a bioinformatics-based structural model for a C15 isolate. The model showed the VP1-3 capsid proteins retain their fundamental cores relative to the RV-A+B, but conserved, internal RV-C residues affect the shape and charge of the VP1 hydrophobic pocket that confers antiviral drug susceptibility. When predictions of the model were tested in organ cultures or ALI systems with recombinant C15 virus, there was a resistance to capsid-binding drugs, including pleconaril, BTA-188, WIN56291, WIN52035 and WIN52084. Unique to all RV-C, the model predicts conserved amino acids within the pocket and capsid surface pore leading to the pocket may correlate with this activity.
    Full-text · Article · Jan 2014 · Virology
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