scholarly journals Unravelling the requirement for host cell chloride channels during HRSV infection

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Hayley Pearson ◽  
John Barr ◽  
Jamel Mankouri
Keyword(s):  
Chloride Channels ◽  
Single Channel ◽  
Treatment Options ◽  
Virus Multiplication ◽  
Respiratory Pathogens ◽  
Multiplication Cycle ◽  
Cl Channels ◽  
Syncytial Virus ◽  
The Uk ◽  
Tract Infections

Ion channels are a diverse class of transmembrane proteins that selectively allow ions across membranes, influencing a multitude of cellular processes. Modulation of these channels by viruses is emerging as an important host-pathogen interaction that regulates critical stages of the virus multiplication cycle including entry, replication and egress. Human respiratory syncytial virus (HRSV) causes severe respiratory tract infections globally and is one of the most lethal respiratory pathogens for infants in developing countries, with frequent development of bronchiolitis. Furthermore, it is the most significant cause of hospitalisation of infants in the UK. Evidence also indicates that severe childhood HRSV infection contributes towards the increased incidence of adult asthma. No HRSV vaccine is available, and currently the only treatment is immunoprophylaxis which is prohibitively expensive and only moderately effective; thus new treatment options are required. Utilising GFP-expressing HRSV in combination with an extensive panel of channel specific pharmacological inhibitors, we have identified an important role of cellular chloride (Cl-) channels during HRSV infection. Interestingly, pharmacological inhibition of specific Cl- channel families has ruled out involvement of the CFTR and instead highlighted a critical requirement for calcium-activated Cl- channels (CaCCs). Time of addition studies using CaCC blockers have indicated that these channels play a post-entry role during HRSV infection. Using genetic knockdown techniques we have isolated a single channel of interest and are now further investigating its role in facilitating HRSV multiplication, as well as assessing the importance of Cl- channels in replication cycles of other negative sense RNA viruses.

scholarly journals Bacterial and Viral Coinfections with the Human Respiratory Syncytial Virus

2021 ◽  
Vol 9 (6) ◽  
pp. 1293
Author(s):  
Gaspar A. Pacheco ◽  
Nicolás M. S. Gálvez ◽  
Jorge A. Soto ◽  
Catalina A. Andrade ◽  
Alexis M. Kalergis
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Human Respiratory Syncytial Virus ◽  
Respiratory Pathogens ◽  
Parainfluenza Viruses ◽  
Starting Point ◽  
The Social ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Polymicrobial Infections

The human respiratory syncytial virus (hRSV) is one of the leading causes of acute lower respiratory tract infections in children under five years old. Notably, hRSV infections can give way to pneumonia and predispose to other respiratory complications later in life, such as asthma. Even though the social and economic burden associated with hRSV infections is tremendous, there are no approved vaccines to date to prevent the disease caused by this pathogen. Recently, coinfections and superinfections have turned into an active field of study, and interactions between many viral and bacterial pathogens have been studied. hRSV is not an exception since polymicrobial infections involving this virus are common, especially when illness has evolved into pneumonia. Here, we review the epidemiology and recent findings regarding the main polymicrobial infections involving hRSV and several prevalent bacterial and viral respiratory pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, human rhinoviruses, influenza A virus, human metapneumovirus, and human parainfluenza viruses. As reports of most polymicrobial infections involving hRSV lack a molecular basis explaining the interaction between hRSV and these pathogens, we believe this review article can serve as a starting point to interesting and very much needed research in this area.

scholarly journals Impact of Rhinovirus Infections in Children

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 521 ◽  
Author(s):  
Silvia Vandini ◽  
Carlotta Biagi ◽  
Maximilian Fischer ◽  
Marcello Lanari
Keyword(s):  
Rna Virus ◽  
Pediatric Population ◽  
Treatment Options ◽  
Respiratory Morbidity ◽  
Upper Respiratory Tract ◽  
Direct Cell ◽  
The Subject ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection’s epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.

scholarly journals Heterogeneity of chloride channels in the apical membrane of isolated mitochondria-rich cells from toad skin.

1996 ◽  
Vol 108 (5) ◽  
pp. 421-433 ◽  
Author(s):  
J B Sørensen ◽  
E H Larsen
Keyword(s):  
Chloride Channels ◽  
Single Channel ◽  
Apical Membrane ◽  
Single Cells ◽  
Membrane Depolarization ◽  
Equilibrium Potential ◽  
Toad Skin ◽  
Patch Clamp Technique ◽  
Cl Channels ◽  
Inside Out

The isolated epithelium of toad skin was disintegrated into single cells by treatment with collagenase and trypsine. Chloride channels of cell-attached and excised inside-out apical membrane-patches of mitochondria-rich cells were studied by the patch-clamp technique. The major population of Cl- channels constituted small 7-pS linear channels in symmetrical solutions (125 mM Cl-). In cell-attached and inside-out patches the single channel i/V-relationship could be described by electrodiffusion of Cl- with a Goldmann-Hodgkin-Katz permeability of, PCl = 1.2 x 10(-14) - 2.6 x 10(-14) cm3. s-1. The channel exhibited voltage-independent activity and could be activated by cAMP. This channel is a likely candidate for mediating the well known cAMP-induced transepithelial Cl- conductance of the amphibian skin epithelium. Another population of Cl- channels exhibited large, highly variable conductances (upper limit conductances, 150-550 pS) and could be activated by membrane depolarization. A group of intermediate-sized Cl(-)-channels included: (a) channels (mean conductance, 30 pS) with linear or slightly outwardly rectifying i/V-relationships and activity occurring in distinct "bursts," (b) channels (conductance-range, 10-27 pS) with marked depolarization-induced activity, and (c) channels with unresolvable kinetics. The variance of current fluctuations of such "noisy" patches exhibited a minimum close to the equilibrium-potential for Cl-. With channels occurring in only 38% of sealed patches and an even lower frequency of voltage-activated channels, the chloride conductance of the apical membrane of mitochondria-rich cells did not match quantitatively that previously estimated from macroscopic Ussing-chamber experiments. From a qualitative point of view, however, we have succeeded in demonstrating the existence of Cl-channels in the apical membrane with features comparable to macroscopic predictions, i.e., activation of channel gating by cAMP and, in a few patches, also by membrane depolarization.

scholarly journals Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients

2017 ◽  
Author(s):  
C Langelier ◽  
MS Zinter ◽  
K Kalantar ◽  
GA Yanik ◽  
S Christenson ◽  
...  
Keyword(s):  
Pathogen Detection ◽  
Respiratory Infections ◽  
Human Herpesvirus ◽  
Microbial Pathogens ◽  
Respiratory Pathogens ◽  
Metagenomic Sequencing ◽  
Respiratory Illnesses ◽  
Standard Testing ◽  
Syncytial Virus ◽  
Tract Infections

ABSTRACTRATIONALECurrent microbiologic diagnostics often fail to identify the etiology of lower respiratory tract infections (LRTI) in hematopoietic cellular transplant recipients (HCT), which precludes the implementation of targeted therapies.OBJECTIVESTo address the need for improved LRTI diagnostics, we evaluated the utility of metagenomic next generation sequencing (mNGS) of bronchoalveolar lavage (BAL) to detect microbial pathogens in HCT patients with acute respiratory illnesses.METHODSWe enrolled 22 post-HCT adults ages 19-69 years with acute respiratory illnesses who underwent BAL at the University of Michigan between January 2012 and May 2013. mNGS was performed on BAL fluid to detect microbes and simultaneously assess the host transcriptional response. Results were compared against conventional microbiologic assays.MEASUREMENTS & MAIN RESULTSmNGS demonstrated 100% sensitivity for detecting respiratory microbes (human metapneumovirus, respiratory syncytial virus,Stenotrophomonas maltophilia, human herpesvirus 6 and cytomegalovirus) when compared to standard testing. Previously unrecognized LRTI pathogens were identified in six patients for whom standard testing was negative (human coronavirus 229E, human rhinovirus A,Corynebacterium propinquumandStreptococcus mitis); findings were confirmed by independent PCR and 16S rRNA sequencing. Relative to patients without infection, patients with infection had increased expression of immunity related genes (p=0.022) and significantly lower diversity of their respiratory microbiome (p=0.017).CONCLUSIONSCompared to conventional diagnostics, mNGS enhanced detection of pathogens in BAL fluid from HCT patients. Furthermore, our results suggest that combining unbiased microbial pathogen detection with assessment of host gene biomarkers of immune response may hold promise for enhancing the diagnosis of post-HCT respiratory infections.

scholarly journals Modelling hospital admissions for lower respiratory tract infections in the elderly in England

2006 ◽  
Vol 134 (6) ◽  
pp. 1150-1157 ◽  
Author(s):  
B. MÜLLER-PEBODY ◽  
N. S. CROWCROFT ◽  
M. C. ZAMBON ◽  
W. J. EDMUNDS
Keyword(s):  
Respiratory Tract ◽  
Elderly Patients ◽  
Lower Respiratory Tract ◽  
Hospital Admissions ◽  
Vaccine Development ◽  
Whooping Cough ◽  
Linear Regression Analysis ◽  
Respiratory Pathogens ◽  
Syncytial Virus ◽  
Tract Infections

Despite the importance of lower respiratory-tract infection (LRI) in causing hospitalizations in elderly patients ([ges ]65 years of age) and recent advances in vaccine development, a complete picture of the causative organisms is not available. All hospital discharge diagnoses (ICD-10 code) for LRI in elderly patients in England during 1995–1998 were reviewed. Using known seasonality in potential causative agents of LRI, the contribution of different respiratory pathogens to hospitalizations coded as ‘unspecified LRI’ was estimated by multiple linear regression analysis. Ninety-seven per cent of 551633 LRI-associated diagnoses had no specific organism recorded. From the statistical model the estimated proportions of admissions attributable to different pathogens were applied to calculate estimated hospitalization rates: 93·9 hospitalizations/10000 population aged [ges ]65 years due to S. pneumoniae, 22·9 to influenza virus, 22·3 to H. influenzae, 17·0 to whooping cough, and 12·8 to respiratory syncytial virus. There is enormous potential to improve health using existing vaccines and those under development.

scholarly journals Evaluation of Human Respiratory Syncytial Virus and Human Parainfluenza Virus Type 3 among Hospitalized Children in Northwest of Iran

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Zahra Ramezannia ◽  
Javid Sadeghi ◽  
Shahram Abdoli Oskouie ◽  
Mohammad Ahangarzadeh Rezaee ◽  
Hossein Bannazadeh Baghi ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
Winter Season ◽  
Human Respiratory Syncytial Virus ◽  
Respiratory Pathogens ◽  
Limited Information ◽  
Syncytial Virus ◽  
Tract Infections

Background. Acute respiratory tract infections (ARTIs) are the leading cause of illnesses in children. Human respiratory syncytial virus (HRSV) and human parainfluenza viruses (HPIVs) are among the most common etiologic agents associated with viral respiratory tract infections in children worldwide. Nevertheless, limited information is available on the spread of infections of these two viruses in northwest Iran. Objective. The purpose of the current study is to evaluate the frequency of RSV and HPIV-3 and clinical features among Iranian children with confirmed respiratory infections between April 2019 and March 2020. Methods. 100 nasopharyngeal swabs were collected from hospitalized patients (under 5 years old) with ARTI from Tabriz Children’s Hospital. Detection of respiratory viruses was performed using the nested RT-PCR method. Results. Respiratory syncytial virus and HPIV-3 were recognized in 18% (18/100) and 2% (2/100) of children, respectively. Ten (55.6%) of the RSV-positive samples were male, while 8 (44.4%) were female. HPIV‐3 was found only among 2 male patients (100%). Most patients (61.1%) with RSV infection were less than 12 months old. Additionally, samples that were positive for HPIV-3 were less than 12 months old. RSV infections had occurred mainly during the winter season. Conclusions. This study confirms that RSV can be one of the important respiratory pathogens in children in northwestern Iran. However, according to this study, HPIV-3 has a lower prevalence among children in this area than RSV. Therefore, implementing a routine diagnosis for respiratory pathogens can improve the management of respiratory infections in children.

Small linear chloride channels are endogenous to nonepithelial cells

1992 ◽  
Vol 263 (3) ◽  
pp. C708-C713 ◽  
Author(s):  
S. E. Gabriel ◽  
E. M. Price ◽  
R. C. Boucher ◽  
M. J. Stutts
Keyword(s):  
Cell Lines ◽  
Chloride Channels ◽  
Single Channel ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Cell Types ◽  
Ovary Cells ◽  
3T3 Fibroblasts ◽  
Whole Cell Patch Clamp ◽  
Cl Channels

We used both single-channel and whole cell patch-clamp techniques to characterize chloride channels and currents endogenous to Sf9 cells, 3T3 fibroblasts, and Chinese hamster ovary cells. In cell-attached patches from these cell types, anion channels were observed with low ohmic conductance (4-11 ps), linear current-voltage relationships, and little time- or voltage-dependent behavior. These channels are very similar to the Cl- channels reported to appear concomitant with the expression of cystic fibrosis transmembrane conductance regulator (CFTR) in these cell lines. The presence of such endogenous channels suggests either that low levels of CFTR are present in all of these cell lines prior to transfection or that an endogenous non-CFTR channel is present in these cell types. Our results suggest that at least some of the channel behaviors attributed to expressed, recombinant CFTR in previous studies may have been due to these endogenous Cl- channels.

scholarly journals Role of Respiratory Syncytial Virus in Pediatric Pneumonia

2020 ◽  
Vol 8 (12) ◽  
pp. 2048
Author(s):  
Sonia Bianchini ◽  
Ettore Silvestri ◽  
Alberto Argentiero ◽  
Valentina Fainardi ◽  
Giovanna Pisi ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Young Children ◽  
Respiratory Infections ◽  
Clinical Signs ◽  
Supportive Therapy ◽  
Respiratory Pathogens ◽  
Single Polymerase Chain Reaction ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory viral infections represent the leading cause of hospitalization in infants and young children worldwide and the second leading cause of infant mortality. Among these, Respiratory Syncytial Virus (RSV) represents the main cause of lower respiratory tract infections (LRTIs) in young children worldwide. RSV manifestation can range widely from mild upper respiratory infections to severe respiratory infections, mainly bronchiolitis and pneumonia, leading to hospitalization, serious complications (such as respiratory failure), and relevant sequalae in childhood and adulthood (wheezing, asthma, and hyperreactive airways). There are no specific clinical signs or symptoms that can distinguish RSV infection from other respiratory pathogens. New multiplex platforms offer the possibility to simultaneously identify different pathogens, including RSV, with an accuracy similar to that of single polymerase chain reaction (PCR) in the majority of cases. At present, the treatment of RSV infection relies on supportive therapy, mainly consisting of oxygen and hydration. Palivizumab is the only prophylactic method available for RSV infection. Advances in technology and scientific knowledge have led to the creation of different kinds of vaccines and drugs to treat RSV infection. Despite the good level of these studies, there are currently few registered strategies to prevent or treat RSV due to difficulties related to the unpredictable nature of the disease and to the specific target population.

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