scholarly journals Host Transcription Profiles upon Primary Respiratory Syncytial Virus Infection

2007 ◽  
Vol 81 (11) ◽  
pp. 5958-5967 ◽  
Author(s):  
Riny Janssen ◽  
Jeroen Pennings ◽  
Hennie Hodemaekers ◽  
Annemarie Buisman ◽  
Marijke van Oosten ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Lymph Nodes ◽  
Viral Replication ◽  
Transcriptional Level ◽  
Type I ◽  
Lung Pathology ◽  
Transcription Profiles ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in children. Severe RSV disease is related to an inappropriate immune response to RSV resulting in enhanced lung pathology which is influenced by host genetic factors. To gain insight into the early pathways of the pathogenesis of and immune response to RSV infection, we determined the transcription profiles of lungs and lymph nodes on days 1 and 3 after infection of mice. Primary RSV infection resulted in a rapid but transient innate, proinflammatory response, as exemplified by the induction of a large number of type I interferon-regulated genes and chemokine genes, genes involved in inflammation, and genes involved in antigen processing. Interestingly, this response is much stronger on day 1 than on day 3 after infection, indicating that the strong transcriptional response in the lung precedes the peak of viral replication. Surprisingly, the set of down-regulated genes was small and none of these genes displayed strong down-regulation. Responses in the lung-draining lymph nodes were much less prominent than lung responses and are suggestive of NK cell activation. Our data indicate that at time points prior to the peak of viral replication and influx of inflammatory cells, the local lung response, measured at the transcriptional level, has already dampened down. The processes and pathways induced shortly after RSV infection can now be used for the selection of candidate genes for human genetic studies of children with severe RSV infection.

scholarly journals Alveolar Macrophages Can Control Respiratory Syncytial Virus Infection in the Absence of Type I Interferons

2016 ◽  
Vol 8 (5) ◽  
pp. 452-463 ◽  
Author(s):  
Spyridon Makris ◽  
Monika Bajorek ◽  
Fiona J. Culley ◽  
Michelle Goritzka ◽  
Cecilia Johansson
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Replication ◽  
Alveolar Macrophages ◽  
Ex Vivo ◽  
Type I Interferons ◽  
Type I ◽  
Proinflammatory Mediators ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections. Immunity to RSV is initiated upon detection of the virus by pattern recognition receptors, such as RIG-I-like receptors. RIG-I-like receptors signal via MAVS to induce the synthesis of proinflammatory mediators, including type I interferons (IFNs), which trigger and shape antiviral responses and protect cells from infection. Alveolar macrophages (AMs) are amongst the first cells to encounter invading viruses and the ones producing type I IFNs. However, it is unclear whether IFNs act to prevent AMs from serving as vehicles for viral replication. In this study, primary AMs from MAVS (Mavs-/-)- or type I IFN receptor (Ifnar1-/-)-deficient mice were exposed to RSV ex vivo. Wild-type (wt) AMs but not Mavs-/- and Ifnar1-/- AMs produced inflammatory mediators in response to RSV. Furthermore, Mavs-/- and Ifnar1-/- AMs accumulated more RSV proteins than wt AMs, but the infection was abortive. Thus, RIG-I-like receptor-MAVS and IFNAR signalling are important for the induction of proinflammatory mediators from AMs upon RSV infection, but this signalling is not central for controlling viral replication. The ability to restrict viral replication makes AMs ideal sensors of RSV infection and important initiators of immune responses in the lung.

scholarly journals Gene Expression Differences in Lungs of Mice during Secondary Immune Responses to Respiratory Syncytial Virus Infection

2010 ◽  
Vol 84 (18) ◽  
pp. 9584-9594 ◽  
Author(s):  
Annemieke Schuurhof ◽  
Louis Bont ◽  
Jeroen L. A. Pennings ◽  
Hennie M. Hodemaekers ◽  
Piet W. Wester ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Transcription Profiles ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Induced Immunity

ABSTRACT Vaccine-induced immunity has been shown to alter the course of a respiratory syncytial virus (RSV) infection both in murine models and in humans. To elucidate which mechanisms underlie the effect of vaccine-induced immunity on the course of RSV infection, transcription profiles in the lungs of RSV-infected mice were examined by microarray analysis. Three models were used: RSV reinfection as a model for natural immunity, RSV challenge after formalin-inactivated RSV vaccination as a model for vaccine-enhanced disease, and RSV challenge following vaccination with recombinant RSV virus lacking the G gene (ΔG-RSV) as a model for vaccine-induced immunity. Gene transcription profiles, histopathology, and viral loads were analyzed at 1, 2, and 5 days after RSV challenge. On the first 2 days after challenge, all mice displayed an expression pattern in the lung similar of that found in primary infection, showing a strong innate immune response. On day 5 after RSV reinfection or after challenge following ΔG-RSV vaccination, the innate immune response was waning. In contrast, in mice with vaccine-enhanced disease, the innate immune response 5 days after RSV challenge was still present even though viral replication was diminished. In addition, only in this group was Th2 gene expression induced. These findings support a hypothesis that vaccine-enhanced disease is mediated by prolonged innate immune responses and Th2 polarization in the absence of viral replication.

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 Crawling with Virus: Translational Insights from a Neonatal Mouse Model on the Pathogenesis of Respiratory Syncytial Virus in Infants

2015 ◽  
Vol 90 (1) ◽  
pp. 2-4 ◽  
Author(s):  
Dahui You ◽  
Jordy Saravia ◽  
David Siefker ◽  
Bishwas Shrestha ◽  
Stephania A. Cormier
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Mouse Model ◽  
Severe Infection ◽  
Neonatal Mouse ◽  
Cell Type ◽  
Human Infants ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Infant Immune Response

The infant immune response to respiratory syncytial virus (RSV) remains incompletely understood. Here we review the use of a neonatal mouse model of RSV infection to mimic severe infection in human infants. We describe numerous age-specific responses, organized by cell type, observed in RSV-infected neonatal mice and draw comparisons (when possible) to human infants.

RESPIRATORY SYNCYTIAL VIRUS LUNG INFECTION IN INFANTS: IMMUNOREGULATORY ROLE OF INFECTED ALVEOLAR MACROPHAGES

PEDIATRICS ◽  
1995 ◽  
Vol 96 (2) ◽  
pp. 391-391
Author(s):  
Leon S. Greos
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Lung Infection ◽  
Local Immune Response ◽  
Rsv Infection ◽  
Syncytial Virus

Alveolar macrophages are infected by RSV in vivo and coexpress potent immunomodulatory molecules that potentially regulate local immune response or lung injury caused by RSV infection.

scholarly journals Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus.

1988 ◽  
Vol 168 (3) ◽  
pp. 1163-1168 ◽  
Author(s):  
M J Cannon ◽  
P J Openshaw ◽  
B A Askonas
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
Cell Line ◽  
Respiratory Disease ◽  
Cytotoxic T Cells ◽  
Lung Pathology ◽  
Class I Mhc ◽  
Rsv Infection ◽  
Syncytial Virus

We have examined the function of class I MHC-restricted cytotoxic T cells in experimental respiratory syncytial virus (RSV) infection of BALB/c mice by transfer of T cell line MJC-A2 and CTL clone E8a into RSV-infected mice. The T cell line cleared pulmonary RSV infection within 5 d in persistently infected gamma-irradiated mice, but caused acute respiratory disease. This was only seen in infected mice and was often lethal after transfer of greater than 3 x 10(6) CTL. Lower numbers of CTL produced less severe disease but still cleared lung RSV, albeit over a longer time course (up to 10 d). Clearance of lung RSV in immunocompetent mice by the T cell line and CTL clone was again accompanied by acute and sometimes lethal respiratory disease. Bronchoalveolar lavage showed severe lung hemorrhage and frequent neutrophil efflux in mice with CTL-augmented disease.

scholarly journals The Human Immune Response to Respiratory Syncytial Virus Infection

2017 ◽  
Vol 30 (2) ◽  
pp. 481-502 ◽  
Author(s):  
Clark D. Russell ◽  
Stefan A. Unger ◽  
Marc Walton ◽  
Jürgen Schwarze
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
T Cell Response ◽  
Rsv Infection ◽  
Human Immune Response ◽  
Ifn Γ ◽  
Human Immune ◽  
Syncytial Virus

SUMMARY Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8+ T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8+ T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.

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 Antiviral Efficacy of a Respiratory Syncytial Virus (RSV) Fusion Inhibitor in a Bovine Model of RSV Infection

2015 ◽  
Vol 59 (8) ◽  
pp. 4889-4900 ◽  
Author(s):  
Robert Jordan ◽  
Matt Shao ◽  
Richard L. Mackman ◽  
Michel Perron ◽  
Tomas Cihlar ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Structural Analog ◽  
Therapeutic Benefit ◽  
Viral Envelope ◽  
Fusion Inhibitor ◽  
Lung Pathology ◽  
Host Cell Membrane ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACTRespiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Effective treatment for RSV infection is a significant unmet medical need. While new RSV therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human RSV, making it difficult to evaluate new disease interventions. Experimental infection of Holstein calves with bovine RSV (bRSV) causes a severe respiratory infection that is similar to human RSV infection, providing a relevant model for testing novel therapeutic agents. In this model, viral load is readily detected in nasal secretions by quantitative real-time PCR (qRT-PCR), and cumulative symptom scoring together with histopathology evaluations of infected tissue allow for the assessment of disease severity. The bovine RSV model was used to evaluate the antiviral activity of an RSV fusion inhibitor, GS1, which blocks virus entry by inhibiting the fusion of the viral envelope with the host cell membrane. The efficacy of GS1, a close structural analog of GS-5806 that is being developed to treat RSV infection in humans was evaluated in two randomized, blind, placebo-controlled studies in bRSV-infected calves. Intravenous administration of GS1 at 4 mg/kg of body weight/day for 7 days starting 24 h or 72 h postinoculation provided clear therapeutic benefit by reducing the viral load, disease symptom score, respiration rate, and lung pathology associated with bRSV infection. These data support the use of the bovine RSV model for evaluation of experimental therapeutics for treatment of RSV.

scholarly journals Respiratory syncytial virus is associated with an inflammatory response in lungs and architectural remodeling of lung-draining lymph nodes of newborn lambs

2011 ◽  
Vol 300 (1) ◽  
pp. L12-L24 ◽  
Author(s):  
Fatoumata B. Sow ◽  
Jack M. Gallup ◽  
Alicia Olivier ◽  
Subramaniam Krishnan ◽  
Andriani C. Patera ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lymph Nodes ◽  
Transcriptional Response ◽  
Lymphoid Hyperplasia ◽  
Interferon Response ◽  
Lung Macrophage ◽  
Rsv Infection ◽  
Tracheobronchial Lymph Nodes ◽  
Syncytial Virus ◽  
Draining Lymph Nodes

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in children worldwide. The understanding of neonatal RSV pathogenesis depends on using an animal model that reproduces neonatal RSV disease. Previous studies from us and others demonstrated that the neonatal lamb model resembles human neonatal RSV infection. Here, we provide an extensive and detailed characterization of the histopathology, viral load, cellular infiltration, and cytokine production in lungs and tracheobronchial lymph nodes of lambs inoculated with human RSV strain A2 over the course of infection. In the lung, RSV titers were low at day 3 postinfection, increased significantly by day 6, and decreased to baseline levels at day 14. Infection in the lung was associated with an accumulation of macrophages, CD4+ and CD8+ T cells, and a transcriptional response of genes involved in inflammation, chemotaxis, and interferon response, characterized by increased IFNγ, IL-8, MCP-1, and PD-L1, and decreased IFNβ, IL-10, and TGF-β. Laser capture microdissection studies determined that lung macrophage-enriched populations were the source of MCP-1 but not IL-8. Immunoreactivity to caspase 3 occurred within bronchioles and alveoli of day 6-infected lambs. In lung-draining lymph nodes, RSV induced lymphoid hyperplasia, suggesting an ability of RSV to enhance lymphocytic proliferation and differentiation pathways. This study suggests that, in lambs with moderate clinical disease, RSV enhances the activation of caspase cell death and Th1-skewed inflammatory pathways, and complements previous observations that emphasize the role of inflammation in the pathogenesis of RSV disease.

Sign in / Sign up

Export Citation Format

Share Document