Interactions between respiratory syncytial virus and the host cell: opportunities for antivirus strategies?

2006 ◽  
Vol 8 (21) ◽  
pp. 1-17 ◽  
Author(s):  
Richard J. Sugrue
Keyword(s):  
Respiratory Syncytial Virus ◽  
Host Cell ◽  
The Elderly ◽  
Paediatric Population ◽  
Health Concern ◽  
Effective Vaccine ◽  
Rsv Infection ◽  
Host Cell Factors ◽  
Syncytial Virus ◽  
Virus Replication Cycle

At the start of the 21st century, respiratory syncytial virus (RSV) remains a serious global health concern. Although RSV has traditionally been acknowledged as a leading cause of morbidity and mortality in the paediatric population, the elderly and people with suppressed immune systems are now also recognised as being at risk from serious RSV infection. This problem is currently exacerbated by the lack of an effective vaccine to prevent RSV infection. Although the virus proteins play a variety of roles during the virus replication cycle, in many cases these tasks are performed via specific interactions with host-cell factors, including proteins, carbohydrates and lipids. The way in which RSV interacts with the host cell is currently being examined using a battery of different techniques, which encompass several scientific disciplines. This is providing new and interesting insights into how RSV interacts with the host cell at the molecular level, which in turn is offering the hope of new strategies to prevent RSV infection.

scholarly journals Contribution of Dendritic Cells in Protective Immunity against Respiratory Syncytial Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 102 ◽  
Author(s):  
Hi Eun Jung ◽  
Tae Hoon Kim ◽  
Heung Kyu Lee
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Defense Mechanisms ◽  
Adaptive Immune Response ◽  
The Elderly ◽  
Effective Vaccine ◽  
Adaptive Immune ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. The socioeconomic burden of RSV infection is substantial because it leads to serious respiratory problems, subsequent hospitalization, and mortality. Despite its clinical significance, a safe and effective vaccine is not yet available to prevent RSV infection. Upon RSV infection, lung dendritic cells (DCs) detecting pathogens migrate to the lymph nodes and activate the adaptive immune response. Therefore, RSV has evolved various immunomodulatory strategies to inhibit DC function. Due to the capacity of RSV to modulate defense mechanisms in hosts, RSV infection results in inappropriate activation of immune responses resulting in immunopathology and frequent reinfection throughout life. This review discusses how DCs recognize invading RSV and induce adaptive immune responses, as well as the regulatory mechanisms mediated by RSV to disrupt DC functions and ultimately avoid host defenses.

scholarly journals An epitope-specific chemically defined nanoparticle vaccine for respiratory syncytial virus

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Armando Zuniga ◽  
Oliver Rassek ◽  
Melissa Vrohlings ◽  
Aniebrys Marrero-Nodarse ◽  
Kerstin Moehle ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibodies ◽  
The Elderly ◽  
Effective Vaccine ◽  
Lung Pathology ◽  
Nanoparticle Delivery ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Safety Features ◽  
Preclinical Animal Models

AbstractRespiratory syncytial virus (RSV) can cause severe respiratory disease in humans, particularly in infants and the elderly. However, attempts to develop a safe and effective vaccine have so far been unsuccessful. Atomic-level structures of epitopes targeted by RSV-neutralizing antibodies are now known, including that bound by Motavizumab and its clinically used progenitor Palivizumab. We developed a chemically defined approach to RSV vaccine design, that allows control of both immunogenicity and safety features of the vaccine. Structure-guided antigen design and a synthetic nanoparticle delivery platform led to a vaccine candidate that elicits high titers of palivizumab-like, epitope-specific neutralizing antibodies. The vaccine protects preclinical animal models from RSV infection and lung pathology typical of vaccine-derived disease enhancement. The results suggest that the development of a safe and effective synthetic epitope-specific RSV vaccine may be feasible by combining this conformationally stabilized peptide and synthetic nanoparticle delivery system.

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.

scholarly journals Antibiotic Minocycline Prevents Respiratory Syncytial Virus Infection

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 739 ◽  
Author(s):  
Swapnil S. Bawage ◽  
Pooja M. Tiwari ◽  
Shreekumar Pillai ◽  
Vida A. Dennis ◽  
Shree R. Singh
Keyword(s):  
Respiratory Syncytial Virus ◽  
Specific Activity ◽  
The Body ◽  
Effective Vaccine ◽  
Mortality And Morbidity ◽  
Viral Activity ◽  
Immunodeficiency Virus ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Common Respiratory Virus

Treatment drugs, besides their specific activity, often have multiple effects on the body. The undesired effect of the drug may be repurposed as therapeutics, saving significant investigative time and effort. Minocycline has anti-cancer, anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Presently, minocycline is also known to show anti-viral activity against Influenza virus, Japanese encephalitis virus, Simian immunodeficiency virus, Human immunodeficiency virus and West Nile virus. Here, we investigate the effect of minocycline on Respiratory syncytial virus (RSV), a common respiratory virus that causes severe mortality and morbidity in infants, children, and older adult populations. Currently, there is no effective vaccine or treatment for RSV infection; hence, there is a critical need for alternative and effective drug choices. Our study shows that minocycline reduces the RSV-mediated cytopathic effect and prevents RSV infection. This is the first study demonstrating the anti-viral activity of minocycline against RSV.

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 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 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 Current State and Challenges in Developing Respiratory Syncytial Virus Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 672
Author(s):  
Carlotta Biagi ◽  
Arianna Dondi ◽  
Sara Scarpini ◽  
Alessandro Rocca ◽  
Silvia Vandini ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
High Risk ◽  
Clinical Stage ◽  
Passive Immunization ◽  
The Elderly ◽  
Effective Vaccine ◽  
Stage Of Development ◽  
High Risk Populations ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) is the main cause of acute respiratory tract infections in infants and it also induces significant disease in the elderly. The clinical course may be severe, especially in high-risk populations (infants and elderly), with a large number of deaths in developing countries and of intensive care hospitalizations worldwide. To date, prevention strategies against RSV infection is based on hygienic measures and passive immunization with humanized monoclonal antibodies, limited to selected high-risk children due to their high costs. The development of a safe and effective vaccine is a global health need and an important objective of research in this field. A growing number of RSV vaccine candidates in different formats (particle-based vaccines, vector-based vaccines, subunit vaccines and live-attenuated vaccines) are being developed and are now at different stages, many of them already being in the clinical stage. While waiting for commercially available safe and effective vaccines, immune prophylaxis in selected groups of high-risk populations is still mandatory. This review summarizes the state-of-the-art of the RSV vaccine research and its implications for clinical practice, focusing on the characteristics of the vaccines that reached the clinical stage of development.

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