scholarly journals New Look at RSV Infection: Tissue Clearing and 3D Imaging of the Entire Mouse Lung at Cellular Resolution

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 201
Author(s):  
Maxence Frétaud ◽  
Delphyne Descamps ◽  
Daphné Laubreton ◽  
Marie-Anne Rameix-Welti ◽  
Jean-François Eléouët ◽  
...  
Keyword(s):  
3D Imaging ◽  
The Elderly ◽  
Mouse Lung ◽  
Tissue Clearing ◽  
Host Interactions ◽  
Deep Imaging ◽  
Entire Lung ◽  
Rsv Infection ◽  
Chest X Ray ◽  
Syncytial Virus

Background: Respiratory Syncytial Virus (RSV) is the major cause of severe acute respiratory tract illness in young children worldwide and a main pathogen for the elderly and immune-compromised people. In the absence of vaccines or effective treatments, a better characterization of the pathogenesis of RSV infection is required. To date, the pathophysiology of the disease and its diagnosis has mostly relied on chest X-ray and genome detection in nasopharyngeal swabs. The development of new imaging approaches is instrumental to further the description of RSV spread, virus–host interactions and related acute respiratory disease, at the level of the entire lung. Methods: By combining tissue clearing, 3D microscopy and image processing, we developed a novel visualization tool of RSV infection in undissected mouse lungs. Results: Whole tissue analysis allowed the identification of infected cell subtypes, based on both morphological traits and position within the cellular network. Furthermore, 3D imaging was also valuable to detect the cytoplasmic viral factories, also called inclusion bodies, a hallmark of RSV infection. Conclusions: Whole lung clearing and 3D deep imaging represents an unprecedented visualization method of infected lungs to allow insight into RSV pathophysiology and improve the 2D histology analyses.

scholarly journals New look at RSV infection : tissue clearing and 3D imaging of the entire mouse lung at cellular resolution

2020 ◽  
Author(s):  
Maxence Frétaud ◽  
Delphyne Descamps ◽  
Daphné Laubreton ◽  
Marie-Anne Rameix-Welti ◽  
Jean-François Eléouët ◽  
...  
Keyword(s):  
3D Imaging ◽  
The Elderly ◽  
Mouse Lung ◽  
Tissue Clearing ◽  
Host Interactions ◽  
Deep Imaging ◽  
Entire Lung ◽  
Rsv Infection ◽  
Chest X Ray ◽  
Syncytial Virus

AbstractBackgroundRespiratory Syncytial Virus (RSV) is the major cause of severe acute respiratory tract illness in young children worldwide and a main pathogen for the elderly and immune-compromised people. In the absence of vaccines or effective treatments, a better characterization of the pathogenesis of RSV infection is required. To date, the pathophysiology of the disease and its diagnosis mostly relied on chest x-ray and genome detection in nasopharyngeal swabs. The development of new imaging approaches is instrumental to further the description of RSV spread, virus-host interactions and related acute respiratory disease, at the level of the entire lung.MethodsBy combining tissue clearing, 3D microscopy and image processing, we developed a novel visualization tool of RSV infection in undissected mouse lungs.ResultsWhole tissue analysis allowed the identification of infected cell subtypes, based on both morphological traits and position within the cellular network. Furthermore, 3D imaging was also valuable to detect the cytoplasmic viral factories, also called inclusion bodies, a hallmark of RSV infection.ConclusionsWhole lung clearing and 3D deep-imaging represents an unprecedented visualization method of infected lungs to allow insight into RSV pathophysiology and improve the 2D histology analyses.

scholarly journals Chemokine regulation of inflammation during respiratory syncytial virus infection

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1837 ◽  
Author(s):  
Rinat Nuriev ◽  
Cecilia Johansson
Keyword(s):  
Respiratory Syncytial Virus ◽  
The Elderly ◽  
Infection Process ◽  
Viral Control ◽  
Small Proteins ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Developed World ◽  
Immune Detection

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections especially in infants, immunocompromised individuals and the elderly and is the most common cause of infant hospitalisation in the developed world. The immune responses against RSV are crucial for viral control and clearance but, if dysregulated, can also result in immunopathology and impaired gas exchange. Lung immunity to RSV and other respiratory viruses begins with the recruitment of immune cells from the bloodstream into the lungs. This inflammatory process is controlled largely by chemokines, which are small proteins that are produced in response to innate immune detection of the virus or the infection process. These chemokines serve as chemoattractants for granulocytes, monocytes, lymphocytes and other leukocytes. In this review, we highlight recent advances in the field of RSV infection and disease, focusing on how chemokines regulate virus-induced inflammation.

scholarly journals Lentiviral and AAV-mediated Expression of Palivizumab Offer protection against Respiratory Syncytial Virus infection

2021 ◽  
Author(s):  
Agata Antepowicz ◽  
Omar Habib ◽  
Freja Kirsebom ◽  
Cecilia Johansson ◽  
Deborah R. Gill ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vulnerable Populations ◽  
The Elderly ◽  
Complete Protection ◽  
Adeno Associated Virus ◽  
Common Cause ◽  
Immunodeficiency Virus ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Respiratory syncytial virus (RSV) infection is a common cause of hospitalisation in infants and the elderly. Palivizumab prophylaxis is the only approved treatment modality but is costly and only offered to select vulnerable populations. Here, we investigated gene delivery approaches via recombinant adeno-associated virus (rAAV2/8) and simian immunodeficiency virus (rSIV.F/HN) vectors to achieve sustained in vivo production of palivizumab in a murine model. Delivery of palivizumab-expressing vectors 28 days prior to RSV challenge resulted in complete protection from RSV-induced weight loss. This approach offers prophylaxis against RSV infection, allowing for wider use and reduction in treatment costs in vulnerable populations.

Retrospective Review of Clinical and Chest X-Ray Findings in Children Admitted to a Community Hospital for Respiratory Syncytial Virus Infection

2018 ◽  
Vol 57 (14) ◽  
pp. 1686-1692 ◽  
Author(s):  
Denver Niles ◽  
Brett Larsen ◽  
Arvind Balaji ◽  
Dana Delaney ◽  
Elizabeth Campos ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Pediatric Intensive Care ◽  
Clinical Findings ◽  
X Rays ◽  
Radiological Findings ◽  
X Ray ◽  
Severe Group ◽  
Rsv Infection ◽  
Chest X Ray ◽  
Syncytial Virus

Introduction. We performed a retrospective study to evaluate demographics, clinical course, outcome, and radiological findings of children with respiratory syncytial virus (RSV) infection. Methods. Four hundred patients admitted between October 2013 and May 2016 were enrolled. Clinical and radiographic trends were evaluated for association with severity of RSV presentation. Severity was defined as hospitalization >2 days, pediatric intensive care unit admission, or need for mechanical ventilation. Results. Common clinical findings included fever (78.5%), coughing (97%), rhinorrhea/congestion (93%), and hypoxia (44.8%). Hypoxia was seen in 64.7% of the severe group compared with 32.0% in the nonsevere group ( P < .001). Airspace opacification was seen in 49.2% of chest X-rays of the severe group compared with 26.4% in the nonsevere group ( P < .001). Conclusion. Higher incidence of hypoxia or airspace opacification on chest X-ray may be predictors of poorer outcomes for patients with RSV infection.

Humoral immunity to respiratory syncytial virus in young and elderly adults

2009 ◽  
Vol 137 (12) ◽  
pp. 1684-1686 ◽  
Author(s):  
C. TERROSI ◽  
G. Di GENOVA ◽  
B. MARTORELLI ◽  
M. VALENTINI ◽  
M. G. CUSI
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Age Groups ◽  
The Elderly ◽  
Elderly Subjects ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Relationship Of ◽  
The Relationship

SUMMARYRespiratory syncytial virus (RSV) has been demonstrated to cause substantial disease in elderly and immunocompromised subjects. The relationship of serum antibody to RSV infection and the risk of infection in elderly subjects is controversial, thus we evaluated the presence of neutralizing antibodies to RSV in healthy people of different age groups and the correlation with viral protection. Baseline blood samples from 197 subjects aged 20–80 years were analysed for the presence of anti-RSV antibodies either by indirect immunofluorescence and microneutralization test. The percentage of people who had neutralizing antibodies to RSV was significantly higher (P=0·001) in the youngest group (92·51%) compared to the frail group (36·21%). The RSV antibody level tends to wane in some older people; this factor could determine proneness to RSV re-infections in the elderly who are at a greater risk of developing severe respiratory disease.

scholarly journals Novel Respiratory Syncytial Virus-Like Particle Vaccine Composed of the Postfusion and Prefusion Conformations of the F Glycoprotein

2016 ◽  
Vol 23 (6) ◽  
pp. 451-459 ◽  
Author(s):  
Velasco Cimica ◽  
Hélène Boigard ◽  
Bipin Bhatia ◽  
John T. Fallon ◽  
Alexandra Alimova ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Matrix Protein ◽  
Neutralizing Antibody ◽  
The Elderly ◽  
Mouse Lung ◽  
Oil Emulsion ◽  
Cytokines And Chemokines ◽  
Virus Like Particle ◽  
Syncytial Virus

ABSTRACTRespiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants and children and represents an important global health burden for the elderly and the immunocompromised. Despite decades of research efforts, no licensed vaccine for RSV is available. We have developed virus-like particle (VLP)-based RSV vaccines assembled with the human metapneumovirus (hMPV) matrix protein (M) as the structural scaffold and the RSV fusion glycoprotein (F) in either the postfusion or prefusion conformation as its prime surface immunogen. Vaccines were composed of postfusion F, prefusion F, or a combination of the two conformations and formulated with a squalene-based oil emulsion as adjuvant. Immunization with these VLP vaccines afforded full protection against RSV infection and prevented detectable viral replication in the mouse lung after challenge. Analyses of lung cytokines and chemokines showed that VLP vaccination mostly induced the production of gamma interferon (IFN-γ), a marker of the Th1-mediated immune response, which is predominantly required for viral protection. Conversely, immunization with a formalin-inactivated RSV (FI-RSV) vaccine induced high levels of inflammatory chemokines and cytokines of the Th2- and Th17-mediated types of immune responses, as well as severe lung inflammation and histopathology. The VLP vaccines showed restricted production of these immune mediators and did not induce severe bronchiolitis or perivascular infiltration as seen with the FI-RSV vaccine. Remarkably, analysis of the serum from immunized mice showed that the VLP vaccine formulated using a combination of postfusion and prefusion F elicited the highest level of neutralizing antibody and enhanced the Th1-mediated immune response.

scholarly journals Depletion of TAX1BP1 amplifies innate immune responses during respiratory syncytial virus infection

2021 ◽  
Author(s):  
Delphyne Descamps ◽  
Andressa Peres de Oliveira ◽  
Lorène Gonnin ◽  
Sarah Madrières ◽  
Jenna Fix ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Respiratory Infections ◽  
The Elderly ◽  
Cellular Protein ◽  
Innate Immune ◽  
Efficient Treatment ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Nucleoprotein N

Respiratory syncytial virus (RSV) is the main cause of acute respiratory infections in young children, and also has a major impact on the elderly and immunocompromised people. In the absence of a vaccine or efficient treatment, a better understanding of RSV interactions with the host antiviral response during infection is needed. Previous studies revealed that cytoplasmic inclusion bodies (IBs) where viral replication and transcription occur could play a major role in the control of innate immunity during infection by recruiting cellular proteins involved in the host antiviral response. We recently showed that the morphogenesis of IBs relies on a liquid-liquid phase separation mechanism depending on the interaction between viral nucleoprotein (N) and phosphoprotein (P). These scaffold proteins are expected to play a central role in the recruitment of cellular proteins to IBs. Here, we performed a yeast two-hybrid screen using RSV N protein as a bait, and identified the cellular protein TAX1BP1 as a potential partner of this viral protein. This interaction was validated by pulldown and immunoprecipitation assays. We showed that TAX1BP1 suppression has only a limited impact on RSV infection in cell cultures. However, RSV replication is decreased in TAX1BP1-deficient mice (TAX1BP1 KO ), whereas the production of inflammatory and antiviral cytokines is enhanced. In vitro infection of wild-type or TAX1BP1 KO alveolar macrophages confirmed that the innate immune response to RSV infection is enhanced in the absence of TAX1BP1. Altogether, our results suggest that RSV could hijack TAX1BP1 to restrain the host immune response during infection. Importance Respiratory syncytial virus (RSV), which is the leading cause of lower respiratory tract illness in infants, still remains a medical problem in the absence of vaccine or efficient treatment. This virus is also recognized as a main pathogen in the elderly and immunocompromised people, and the occurrence of co-infections (with other respiratory viruses and bacteria) amplifies the risks of developing respiratory distress. In this context, a better understanding of the pathogenesis associated to viral respiratory infections, which depends on both viral replication and the host immune response, is needed. The present study reveals that the cellular protein TAX1BP1, which interacts with the RSV nucleoprotein N, participates in the control of the innate immune response during RSV infection, suggesting that N-TAX1BP1 interaction represents a new target for the development of antivirals.

scholarly journals Tissue clearing and 3D imaging in developmental biology

Development ◽  
2021 ◽  
Vol 148 (18) ◽  
Author(s):  
Alba Vieites-Prado ◽  
Nicolas Renier
Keyword(s):  
Developmental Biology ◽  
Image Analysis ◽  
3D Imaging ◽  
Histological Analysis ◽  
Developmental Stages ◽  
Successful Implementation ◽  
Sample Processing ◽  
Tissue Clearing ◽  
Deep Imaging ◽  
Good Grasp

ABSTRACT Tissue clearing increases the transparency of late developmental stages and enables deep imaging in fixed organisms. Successful implementation of these methodologies requires a good grasp of sample processing, imaging and the possibilities offered by image analysis. In this Primer, we highlight how tissue clearing can revolutionize the histological analysis of developmental processes and we advise on how to implement effective clearing protocols, imaging strategies and analysis methods for developmental biology.

scholarly journals Respiratory Syncytial Virus Infects and Abortively Replicates in the Lungs in Spite of Preexisting Immunity

2007 ◽  
Vol 81 (17) ◽  
pp. 9443-9450 ◽  
Author(s):  
Marina S. Boukhvalova ◽  
Gregory A. Prince ◽  
Jorge C. G. Blanco
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Viral Gene Expression ◽  
The Elderly ◽  
Productive Infection ◽  
Viral Gene ◽  
Rna Transcripts ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a major cause of bronchiolitis and viral pneumonia in young children and a serious health risk in immunocompromised individuals and the elderly. Immunity to RSV is not completely understood. In this work, we established a method for monitoring RSV infection by real-time PCR and applied this method for analysis of RSV replication in vivo in the cotton rat model in naïve animals and in animals rendered immune to RSV by prior RSV infection. We found that even though no virus could be isolated from the lungs of RSV-challenged immune animals, RSV infection in fact took place and an accumulation of viral RNA transcripts was observed. This type of replication, therefore, can be termed “abortive,” as RSV is capable of entering the cells in the lungs of immune animals, yet the production of progeny viruses is impaired. Similar patterns of RSV gene expression gradient were observed between naïve and reinfected animals, indicating that the skewing of mRNA gradient of viral gene expression, a mechanism documented during latent infection by other viruses, is not likely to be responsible for abortive replication of RSV during reinfection. We found that passive administration of antibodies to RSV prevents productive infection normally accompanied by viral release in the lung, but it does not prevent abortive replication of the virus. To the best of our knowledge, this is the first evidence of abortive replication of RSV in vivo.

scholarly journals The Effect of RSV Infection on the Respiratory Microbiome of Adults

2020 ◽  
Author(s):  
Leah Cuthbertson ◽  
Phillip James ◽  
Maximillian Habibi ◽  
Ryan Thwaites ◽  
Allan Paras ◽  
...  
Keyword(s):  
Bacterial Community ◽  
Respiratory Tract ◽  
Bacterial Load ◽  
16S Rrna Gene Sequencing ◽  
The Elderly ◽  
Asymptomatic Infection ◽  
Rrna Gene ◽  
Microbial Dysbiosis ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in infants. It is being increasingly recognised as a cause of morbidity and mortality in the elderly. Microbial dysbiosis in the respiratory tract has been hypothesized to predispose individuals to severe RSV infection. This study explores changes in the bacterial community over the course of a controlled human challenge study. From 37 healthy adult patients exposed to a challenge inoculum of RSV, throat swabs were collected daily for 10 days during quarantine and on days 14 and 28 post quarantine. Swabs were processed for bacterial and viral quantification and 16S rRNA gene sequencing. Over the course of the study three clinical outcomes were observed; clinical cold (n = 17), asymptomatic infection (n = 6) or no infection (n = 14). These three outcome groups had no significant differences in the bacterial load, diversity or community composition at baseline. Over the twenty-eight days following RSV inoculation no significant changes in the bacterial community were observed between the outcome groups. This study of healthy adults revealed no major changes in the bacterial community of the respiratory tracts following RSV inoculation, suggesting that this microbial community is resilient to viral perturbations.

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