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.

scholarly journals Role of CCL11 in Eosinophilic Lung Disease during Respiratory Syncytial Virus Infection

2005 ◽  
Vol 79 (4) ◽  
pp. 2050-2057 ◽  
Author(s):  
Stephen P. Matthews ◽  
John S. Tregoning ◽  
Anthony J. Coyle ◽  
Tracy Hussell ◽  
Peter J. M. Openshaw
Keyword(s):  
Respiratory Syncytial Virus ◽  
Cytokine Production ◽  
The Elderly ◽  
Viral Pathogen ◽  
Blocking Antibody ◽  
Interleukin 5 ◽  
Lung Eosinophilia ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a major viral pathogen of infants and the elderly. Significant morbidity is caused by an overexuberant mixed lung cell infiltrate, which is thought to be driven by chemokines. One of the main chemotactic mediators responsible for the movement of eosinophils is CCL11 (eotaxin). Using a mouse model of eosinophilic bronchiolitis induced by RSV, we show here that treatment in vivo with a blocking antibody to CCL11 greatly reduces lung eosinophilia and disease severity. In addition, anti-CCL11 caused a striking inhibition of CD4-T-cell influx and shifted cytokine production away from interleukin-5 without reducing the resistance to viral replication. These results suggest that in addition to influencing eosinophil diapedesis and survival, anti-CCL11 has an action on T cells. These studies strengthen the case for anti-CCL11 treatment of Th2-driven diseases.

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 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 High Resolution Analysis of Respiratory Syncytial Virus Infection In Vivo

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 926 ◽  
Author(s):  
Waleed Aljabr ◽  
Stuart Armstrong ◽  
Natasha Y. Rickett ◽  
Georgios Pollakis ◽  
Olivier Touzelet ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
The Elderly ◽  
High Viral Load ◽  
Label Free ◽  
Respiratory Problems ◽  
Viral Loads ◽  
High Resolution Analysis ◽  
Syncytial Virus

Human respiratory syncytial virus (HRSV) is a major cause of pediatric infection and also causes disease in the elderly and those with underlying respiratory problems. There is no vaccine for HRSV and anti-viral therapeutics are not broadly applicable. To investigate the effect of HRSV biology in children, nasopharyngeal aspirates were taken from children with different viral loads and a combined high throughput RNAseq and label free quantitative proteomics approach was used to characterize the nucleic acid and proteins in these samples. HRSV proteins were identified in the nasopharyngeal aspirates from infected children, and their abundance correlated with viral load (Ct value), confirming HRSV infection. Analysis of the HRSV genome indicated that the children were infected with sub-group A virus and that minor variants in nucleotide frequency occurred in discrete clusters along the HRSV genome, and within a patient clustered distinctly within the glycoprotein gene. Data from the samples were binned into four groups; no-HRSV infection (control), high viral load (Ct < 20), medium viral load (Ct = 20–25), and low viral load (Ct > 25). Cellular proteins associated with the anti-viral response (e.g., ISG15) were identified in the nasopharyngeal aspirates and their abundance was correlated with viral load. These combined approaches have not been used before to study HRSV biology in vivo and can be readily applied to the study the variation of virus host interactions.

scholarly journals Characterization of recombinant influenza A virus as a vector expressing respiratory syncytial virus fusion protein epitopes

2014 ◽  
Vol 95 (9) ◽  
pp. 1886-1891 ◽  
Author(s):  
Peirui Zhang ◽  
Hongjing Gu ◽  
Chengrong Bian ◽  
Na Liu ◽  
Zhiwei Li ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Cell Line ◽  
Nuclear Export ◽  
Influenza A ◽  
Haemagglutination Inhibition ◽  
The Elderly ◽  
Ns Gene ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in infants and the elderly, and no vaccine against this virus has yet been licensed. Here, we report a recombinant PR8 influenza virus with the RSV fusion (F) protein epitopes of the subgroup A gene inserted into the influenza virus non-structural (NS) gene (rFlu/RSV/F) that was generated as an RSV vaccine candidate. The rescued viruses were assessed by microscopy and Western blotting. The proper expression of NS1, the NS gene product, and the nuclear export protein (NEP) of rFlu/RSV/F was also investigated using an immunofluorescent assay. The rescued virus replicated well in the MDCK kidney cell line, A549 lung adenocarcinoma cell line and CNE-2Z nasopharyngeal carcinoma cell line. BALB/c mice immunized intranasally with rFlu/RSV/F had specific haemagglutination inhibition antibody responses against the PR8 influenza virus and RSV neutralization test proteins. Furthermore, intranasal immunization with rFlu/RSV/F elicited T helper type 1-dominant cytokine profiles against the RSV strain A2 virus. Taken together, our findings suggested that rFlu/RSV/F was immunogenic in vivo and warrants further development as a promising candidate vaccine.

scholarly journals Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus

Blood ◽  
2007 ◽  
Vol 110 (5) ◽  
pp. 1578-1586 ◽  
Author(s):  
Simon Phipps ◽  
Chuan En Lam ◽  
Suresh Mahalingam ◽  
Matthew Newhouse ◽  
Ruben Ramirez ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Host Defense ◽  
No Production ◽  
Wild Type ◽  
Interleukin 5 ◽  
Virus Clearance ◽  
Lung Dysfunction ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractEosinophils are recruited to the lungs in response to respiratory syncytial virus (RSV) infection; however, their role in promoting antiviral host defense remains unclear. Here, we demonstrate that eosinophils express TLRs that recognize viral nucleic acids, are activated and degranulate after single-stranded RNA (ssRNA) stimulation of the TLR-7–MyD88 pathway, and provide host defense against RSV that is MyD88 dependent. In contrast to wild-type mice, virus clearance from lung tissue was more rapid in hypereosinophilic (interleukin-5 transgenic) mice. Transfer of wild-type but not MyD88-deficient eosinophils to the lungs of RSV-infected wild-type mice accelerated virus clearance and inhibited the development of airways hyperreactivity. Similar responses were observed when infected recipient mice were MyD88 deficient. Eosinophils isolated from infected hypereosinophilic MyD88-sufficient but not MyD88-deficient mice expressed greater amounts of IFN regulatory factor (IRF)–7 and eosinophil-associated ribonucleases EAR-1 and EAR-2. Hypereosinophilia in the airways of infected mice also correlated with increased expression of IRF-7, IFN-β, and NOS-2, and inhibition of NO production with the NOS-2 inhibitor L-NMA partially reversed the accelerated virus clearance promoted by eosinophils. Collectively, our results demonstrate that eosinophils can protect against RSV in vivo, as they promote virus clearance and may thus limit virus-induced lung dysfunction.

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