scholarly journals Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 716 ◽  
Author(s):  
Junsu Ban ◽  
Na-Rae Lee ◽  
Noh-Jin Lee ◽  
Jong Kil Lee ◽  
Fu-Shi Quan ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Infections ◽  
Ectopic Expression ◽  
Suppressive Effect ◽  
Type I ◽  
Antiviral Signaling ◽  
Lower Respiratory Tract Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, several viruses target initial RIG-I activation through ubiquitination. RSV NS1 and NS2 have been shown to interfere with RIG-I-mediated antiviral signaling. In this study, we explored the possibility that NS1 suppresses RIG-I-mediated antiviral signaling by targeting TRIM25. Ubiquitination of ectopically expressed RIG-I-2Cards domain was decreased by RSV infection, indicating that RSV possesses ability to inhibit TRIM25-mediated RIG-I ubiquitination. Similarly, ectopic expression of NS1 sufficiently suppressed TRIM25-mediated RIG-I ubiquitination. Furthermore, interaction between NS1 and TRIM25 was detected by a co-immunoprecipitation assay. Further biochemical assays showed that the SPRY domain of TRIM25, which is responsible for interaction with RIG-I, interacted sufficiently with NS1. Suppression of RIG-I ubiquitination by NS1 resulted in decreased interaction between RIG-I and its downstream molecule, MAVS. The suppressive effect of NS1 on RIG-I signaling could be abrogated by overexpression of TRIM25. Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling.

scholarly journals Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ma. Del Rocío Baños-Lara ◽  
Boyang Piao ◽  
Antonieta Guerrero-Plata
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Viral Infections ◽  
Human Metapneumovirus ◽  
Human Epithelial Cells ◽  
Mucin Expression ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Mucins (MUC) constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

scholarly journals Alveolar-like Macrophages Attenuate Respiratory Syncytial Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1960
Author(s):  
Bárbara N. Porto ◽  
Michael L. Litvack ◽  
Yuchen Cen ◽  
Irene Lok ◽  
Sheena Bouch ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Pluripotent Stem Cells ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Type I ◽  
Intratracheal Administration ◽  
Cell Based Therapy ◽  
Acute Lower Respiratory Infections ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections in young children and infection has been linked to the development of persistent lung disease in the form of wheezing and asthma. Despite substantial research efforts, there are no RSV vaccines currently available and an effective monoclonal antibody targeting the RSV fusion protein (palivizumab) is of limited general use given the associated expense. Therefore, the development of novel approaches to prevent RSV infection is highly desirable to improve pediatric health globally. We have developed a method to generate alveolar-like macrophages (ALMs) from pluripotent stem cells. These ALMs have shown potential to promote airway innate immunity and tissue repair and so we hypothesized that ALMs could be used as a strategy to prevent RSV infection. Here, we demonstrate that ALMs are not productively infected by RSV and prevent the infection of epithelial cells. Prevention of epithelial infection was mediated by two different mechanisms: phagocytosis of RSV particles and release of an antiviral soluble factor different from type I interferon. Furthermore, intratracheal administration of ALMs protected mice from subsequent virus-induced weight loss and decreased lung viral titres and inflammation, indicating that ALMs can impair the pathogenesis of RSV infection. Our results support a prophylactic role for ALMs in the setting of RSV infection and warrant further studies on stem cell-derived ALMs as a novel cell-based therapy for pulmonary viral infections.

Ribavirin. Red Book Committee Recommendations Questioned

PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 672-673
Author(s):  
Ellen R. Wald ◽  
Barry Dashefsky
Keyword(s):  
High Risk ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Disease ◽  
American Academy Of Pediatrics ◽  
Lower Respiratory Tract Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease ◽  
New Guidelines ◽  
Do So

The new guidelines provided by the Committee on Infectious Diseases of the American Academy of Pediatrics on the Use of Ribavirin in the Treatment of Respiratory Syncytial Virus Infection (RSV) are perplexing and prompt concern: "Ribavirin treatment is recommended for the following patients hospitalized with RSV lower respiratory tract disease: a. infants at high risk for severe or complicated RSV infection, including those with complicated congenital heart disease (including pulmonary hypertension); those with bronchopulmonary dysplasia, . . ."1,pp502-503 The accompanying qualifier that "the recommendations in this statement do not indicate an exclusive course of treatment or procedure to be followed"1,p501 is important but insufficient to dampen the effect of the Committee's decision to change its former stance of merely urging consideration of the use of ribavirin for patients at high risk for complications2 to an unequivocal recommendation to do so.

Control of Nosocomial Respiratory Syncytial Viral Infections

PEDIATRICS ◽  
1978 ◽  
Vol 62 (5) ◽  
pp. 728-732
Author(s):  
Caroline Breese Hall ◽  
Joyce M. Geiman ◽  
R. Gordon Douglas ◽  
Mary Pat Meagher
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Infections ◽  
Close Contact ◽  
Initial Infection ◽  
Staff Members ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Repeated Infections

We evaluated methods to control the spread of respiratory syncytial virus (RSV) on our infants' ward during a community outbreak of RSV infection. Methods included isolation and cohorting of infected infants, strict handwashing, use of gowns, and the cohorting of staff to the ill infants. Of 123 infants studied, 36 were admitted with RSV infections. Of the remaining 87 contact infants, eight (19%) acquired nosocomial RSV disease. Three of the eight developed pneumonia and one died. Of the 43 staff members, 24 (56%) became infected and 82% were symptomatic. Four acquired repeated infections within weeks of the initial infection. Studies a year previously had revealed that 45% of contact infants and 42% of the staff had acquired nosocomial RSV infections. Thus, the employed procedures appeared to have decreased the transmission of RSV to infants but not to the staff. Staff may continue to be infected by large droplets from close contact with ill infants or by self-inoculation of contaminated secretions.

scholarly journals Pathogenesis of Respiratory Syncytial Virus Infection in BALB/c Mice Differs Between Intratracheal and Intranasal Inoculation

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 508 ◽  
Author(s):  
Elisabeth A. van Erp ◽  
Anke J. Lakerveld ◽  
H. Lie Mulder ◽  
Willem Luytjes ◽  
Gerben Ferwerda ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Animal Models ◽  
Antiviral Agents ◽  
Mouse Strains ◽  
Immunological Parameters ◽  
Intranasal Inoculation ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease requiring hospitalization in infants. There are no market-approved vaccines or antiviral agents available, but a growing number of vaccines and therapeutics are in (pre)clinical stages of development. Reliable animal models are crucial to evaluate new vaccine concepts, but in vivo RSV research is hampered by the lack of well-characterized animal models that faithfully mimic the pathogenesis of RSV infection in humans. Mice are frequently used in RSV infection and vaccination studies. However, differences in the use of mouse strains, RSV subtypes, and methodology often lead to divergent study outcomes. To our knowledge, a comparison between different RSV inoculation methods in mice has not been described in the literature, even though multiple methods are being used across different studies. In this study, we evaluated various pathological and immunological parameters in BALB/c mice after intratracheal or intranasal inoculation with RSV-A2. Our study reveals that intranasal inoculation induces robust pathology and inflammation, whereas this is not the case for intratracheal inoculation. As immunopathology is an important characteristic of RSV disease in infants, these data suggest that in mice intranasal inoculation is a more appropriate method to study RSV infection than intratracheal inoculation. These findings will contribute to the rational experimental design of future in vivo RSV experiments.

scholarly journals Differential Responses by Human Respiratory Epithelial Cell Lines to Respiratory Syncytial Virus Reflect Distinct Patterns of Infection Control

2018 ◽  
Vol 92 (15) ◽  
Author(s):  
Philippa Hillyer ◽  
Rachel Shepard ◽  
Megan Uehling ◽  
Mina Krenz ◽  
Faruk Sheikh ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Lines ◽  
A549 Cells ◽  
Type I ◽  
Epithelial Cell Lines ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Respiratory Epithelial

ABSTRACT Respiratory syncytial virus (RSV) infects small foci of respiratory epithelial cells via infected droplets. Infection induces expression of type I and III interferons (IFNs) and proinflammatory cytokines, the balance of which may restrict viral replication and affect disease severity. We explored this balance by infecting two respiratory epithelial cell lines with low doses of recombinant RSV expressing green fluorescent protein (rgRSV). A549 cells were highly permissive, whereas BEAS-2B cells restricted infection to individual cells or small foci. After infection, A549 cells expressed higher levels of IFN-β-, IFN-λ-, and NF-κB-inducible proinflammatory cytokines. In contrast, BEAS-2B cells expressed higher levels of antiviral interferon-stimulated genes, pattern recognition receptors, and other signaling intermediaries constitutively and after infection. Transcriptome analysis revealed that constitutive expression of antiviral and proinflammatory genes predicted responses by each cell line. These two cell lines provide a model for elucidating critical mediators of local control of viral infection in respiratory epithelial cells. IMPORTANCE Airway epithelium is both the primary target of and the first defense against respiratory syncytial virus (RSV). Whether RSV replicates and spreads to adjacent epithelial cells depends on the quality of their innate immune responses. A549 and BEAS-2B are alveolar and bronchial epithelial cell lines, respectively, that are often used to study RSV infection. We show that A549 cells are permissive to RSV infection and express genes characteristic of a proinflammatory response. In contrast, BEAS-2B cells restrict infection and express genes characteristic of an antiviral response associated with expression of type I and III interferons. Transcriptome analysis of constitutive gene expression revealed patterns that may predict the response of each cell line to infection. This study suggests that restrictive and permissive cell lines may provide a model for identifying critical mediators of local control of infection and stresses the importance of the constitutive antiviral state for the response to viral challenge.

scholarly journals Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease

2014 ◽  
Vol 89 (3) ◽  
pp. 1564-1578 ◽  
Author(s):  
Yung-Chang Su ◽  
Dijana Townsend ◽  
Lara J. Herrero ◽  
Ali Zaid ◽  
Michael S. Rolph ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
The Elderly ◽  
Pulmonary Eosinophilia ◽  
Recurrent Wheezing ◽  
Interleukin 5 ◽  
Lower Respiratory Tract Disease ◽  
Syncytial Virus ◽  
Tract Disease ◽  
Deficient Mice

ABSTRACTHuman respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood.In vivostudies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin- and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin- and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load.IMPORTANCEThis study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity.

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