Gene Expression Profiles during In Vivo Human Rhinovirus Infection (original) (raw)
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Gene Expression Profiles during In Vivo Human Rhinovirus Infection: Insights into the Host Response
American Journal of Respiratory and Critical Care Medicine, 2008
1 Experimental Rhinovirus Infection: This was a randomized, parallel group study conducted in healthy volunteers with no neutralizing antibody to HRV-16 (titer <2) in a non-sequestered setting. The protocol was approved by the Human Investigations Committee of the University of Virginia and all volunteers gave written, informed consent before participating in the study. A schematic of the study protocol is included in . Subjects were eligible to participate in the study if they were between 18 and 60 years of age, could read, understand and sign the informed consent form, and were healthy based on medical history. Subjects also had to be willing to refrain from taking any allergy or cold medications (including dietary supplements and homepathic preparations indicated for allergy or colds) starting on day -14 and through day 5 of the study. In addition, intranasal medications or treatments were not permitted from day -14 to day 5 and all other medications (except contraceptive preparations or topical acne medications) from day -2 to day 5. Subjects were excluded if they had abnormal nasal anatomy, had experienced cold or allergy symptoms in the previous 2 weeks, had a history of nosebleeds, had used any investigational medication in the past 30 days or had used any tobacco products in the prior 6 months.
Gene Expression Profiles during In Vivo Human Rhinovirus Infection
American Journal of Respiratory and Critical Care Medicine, 2008
1 Experimental Rhinovirus Infection: This was a randomized, parallel group study conducted in healthy volunteers with no neutralizing antibody to HRV-16 (titer <2) in a non-sequestered setting. The protocol was approved by the Human Investigations Committee of the University of Virginia and all volunteers gave written, informed consent before participating in the study. A schematic of the study protocol is included in . Subjects were eligible to participate in the study if they were between 18 and 60 years of age, could read, understand and sign the informed consent form, and were healthy based on medical history. Subjects also had to be willing to refrain from taking any allergy or cold medications (including dietary supplements and homepathic preparations indicated for allergy or colds) starting on day -14 and through day 5 of the study. In addition, intranasal medications or treatments were not permitted from day -14 to day 5 and all other medications (except contraceptive preparations or topical acne medications) from day -2 to day 5. Subjects were excluded if they had abnormal nasal anatomy, had experienced cold or allergy symptoms in the previous 2 weeks, had a history of nosebleeds, had used any investigational medication in the past 30 days or had used any tobacco products in the prior 6 months.
PloS one, 2017
Human rhinovirus (HRV) is the common virus that causes acute respiratory infection (ARI) and is frequently associated with lower respiratory tract infections (LRTIs). We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B). RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi) and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated) were significantly repre...
American Journal of Respiratory Cell and Molecular Biology, 2006
Rhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations. Because the epithelial cell layer is the primary target of RV infection, we hypothesize that RV-induced airway disease is associated with the perturbation of airway epithelial gene expression. In this study, well differentiated primary human airway epithelial cells were infected with either RV16 (major group) or RV1B (minor group). Transcriptional gene profiles from RV-infected and mock-infected control cells were analyzed by Affymetrix Genechip, and changes of the gene expression were confirmed by real-time RT-PCR analysis. At 24 h after infection, 48 genes induced by both viruses were identified. Most of these genes are related to the IFN pathway, and have been documented to have antiviral functions. Indeed, a significant stimulation of IFN- secretion was detected after RV16 infection. Neutralizing antibody specific to IFN- and a specific inhibitor of the Janus kinase pathway both significantly blocked the induction of RV-inducible genes. Further studies demonstrated that 2-aminopurine, a specific inhibitor double-stranded RNA-dependent protein kinase, could block both IFN- production and RV-induced gene expression. Thus, IFN-dependent pathway is a part of the double-stranded RNA-initiated pathway that is responsible for RV-induced gene expression. Consistent with its indispensable role in the induction of antiviral genes, deactivation of this signaling pathway significantly enhanced viral production. Because increase of viral yield is associated with the severity of RV-induced airway illness, the discovery of an epithelial antiviral signaling pathway in this study will contribute to our understanding of the pathogenesis of RV-induced colds and asthma exacerbations.
Mouse respiratory epithelial cells support efficient replication of human rhinovirus
Journal of General Virology, 2003
Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations.
Rhinoviruses as pathogens of the lower respiratory tract
Canadian respiratory journal : journal of the Canadian Thoracic Society
Rhinoviruses (RVs) are the most common upper respiratory pathogens, inducing the majority of common colds worldwide. RV-related morbidity, although significant cumulatively, has been considered trivial for the individual patient. However, recent strong epidemiological associations of RVs with asthma exacerbations, including severe episodes requiring hospitalization, indicate that RV infections can result in serious disease. Current evidence supports the possibility that RVs infect the lower airways, inducing a local inflammatory response. Such evidence suggests that the role of RVs in other lower respiratory diseases, such as pneumonia, bronchitis, bronchiolitis and cystic fibrosis, should be re-examined with polymerase chain reaction-based methodologies, which are considerably more sensitive than traditional, cell culture-based techniques. The mechanisms through which RVs induce lower airway disease are studied to understand the relative contributions of the epithelial, neurogenic ...
Diversity in the bronchial epithelial cell response to infection with different rhinovirus strains
Respirology, 2009
Methods: RV strains, RV-43, RV-48 (major group RV), RV-47 (minor) and EV-68 (enterovirus), were cultured from subjects with acute asthma and compared with the laboratory RV strains, RV-16, RV-14 (major) and RV-1B (minor). Primary bronchial epithelial cells were obtained from healthy control and asthmatic subjects by endobronchial brushing. Response to infection was assessed by the release of IL-6, interferon (IFN)-g induced protein (IP)-10 and IFN-b, as measured by ELISA. Viral replication was assessed by serial titration assays and cell viability by flow cytometry. Results: Major group RV strains and EV-68 all efficiently infected and replicated in epithelial cells causing little cell death. The clinical major group RV strains caused greater release of IL-6 and IP-10 compared with laboratory major group RV strains. Infection with minor group RV resulted in greater release of IP-10, IL-6 and IFN-b that was associated with induction of apoptosis and less efficient viral replication.
An Overview of Innate Immune Response to Human Rhinovirus Infection
Journal of Molecular Virology and Immunology, 2021
Human rhinoviruses (HRV) are mainly associated with catarrh or the common cold and quite possibly cause one of the most unavoidable diseases in human beings. Although the HRV infections of the upper respiratory tract are generally somewhat harmless, there is increasing proof that HRV pave the way for more hazardous infections, promote asthmatic intensifications, and lead to severe diseases in the lower respiratory tract. Respiratory tract epithelial cells are the essential targets for rhinovirus and other respiratory pathogens. In the presence of rhinovirus, respiratory tract epithelial cells mount both supportive of provocative reactions and antiviral natural invulnerable reactions to clear the infection effectively. A portion of antiviral reactions include the expression of interferons (IFNs) and endoplasmic reticulum stress-actuated unfolded protein reaction and autophagy. In patients with chronic (persistent) lung diseases, these reactions may be either imperfect or incited in overabundance prompting insufficient getting free from infection and supported aggravation. In this review, components hidden behind innate antiviral invulnerability and the dysregulation of a portion of these instruments will be examined in patients with chronic lung diseases.
FEMS Immunology & Medical Microbiology
Human L-defensins (hBDs) are antimicrobial peptides that play important roles in host defense against infection, inflammation and immunity. Previous studies showed that microorganisms and proinflammatory mediators regulate the expression of these peptides in airway epithelial cells. The aim of the present study was to investigate the modulation of expression of hBDs in cultured primary bronchial epithelial cells (PBEC) by rhinovirus-16 (RV16), a respiratory virus responsible for the common cold and associated with asthma exacerbations. RV16 was found to induce expression of hBD-2 and-3 mRNA in PBEC, but did not affect hBD-1 mRNA. Viral replication appeared essential for rhinovirus-induced L-defensin mRNA expression, since UV-inactivated rhinovirus did not increase expression of hBD-2 and hBD-3 mRNA. Exposure to synthetic double-stranded RNA (dsRNA) molecule polyinosinic:polycytidylic acid had a similar effect as RV16 on mRNA expression of these peptides in PBEC. In line with this, PBEC were found to express TLR3, a Toll-like receptor involved in recognition of dsRNA. This study shows that rhinovirus infection of PBEC leads to increased hBD-2 and hBD-3 mRNA expression, which may play a role in both the uncomplicated common cold and in virus-associated exacerbations of asthma.