scholarly journals Role of Type I IFNs in the in Vitro Attenuation of Live, Temperature-Sensitive Vaccine Strains of Human Respiratory Syncytial Virus

Virology ◽  
2000 ◽  
Vol 271 (2) ◽  
pp. 390-400 ◽  
Author(s):  
Deborah A. Loveys ◽  
Sandhya Kulkarni ◽  
Prabha L. Atreya
Keyword(s):  
Respiratory Syncytial Virus ◽  
Human Respiratory Syncytial Virus ◽  
Temperature Sensitive ◽  
Type I ◽  
Type I Ifns ◽  
Syncytial Virus

scholarly journals Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

2021 ◽  
Author(s):  
Li-Nan Wang ◽  
Xiang-Lei Peng ◽  
Min Xu ◽  
Yuan-Bo Zheng ◽  
Yue-Ying Jiao ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Gene Deletion ◽  
Human Respiratory Syncytial Virus ◽  
Temperature Sensitive ◽  
T7 Promoter ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractHuman respiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract illness (LRTI), and no vaccine against LRTI has proven to be safe and effective in infants. Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice. The constructed recombinant plasmids harbored (5′ to 3′) a T7 promoter, hammerhead ribozyme, RSV Long strain antigenomic cDNA with cold-passaged (cp) mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain (A2cpts) or further combined with SH gene deletion (A2cptsΔSH), HDV ribozyme (δ), and a T7 terminator. These vectors were subsequently co-transfected with four helper plasmids encoding N, P, L, and M2-1 viral proteins into BHK/T7-9 cells, and the recovered viruses were then passaged in Vero cells. The rescued recombinant RSVs (rRSVs) were named rRSV-Long/A2cp, rRSV-Long/A2cpts, and rRSV-Long/A2cptsΔSH, respectively, and stably passaged in vitro, without reversion to wild type (wt) at sites containing introduced mutations or deletion. Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed  temperature-sensitive (ts) phenotype in vitro and in vivo, all rRSVs were significantly attenuated in vivo. Furthermore, BALB/c mice immunized with rRSVs produced Th1-biased immune response, resisted wtRSV infection, and were free from enhanced respiratory disease. We showed that the combination of ΔSH with attenuation (att) mutations of cpts contributed to improving att phenotype, efficacy, and gene stability of rRSV. By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains, we have laid an important foundation for the development of RSV live attenuated vaccines.

scholarly journals The NS2 Protein of Human Respiratory Syncytial Virus Suppresses the Cytotoxic T-Cell Response as a Consequence of Suppressing the Type I Interferon Response

2006 ◽  
Vol 80 (12) ◽  
pp. 5958-5967 ◽  
Author(s):  
Alexander Kotelkin ◽  
Igor M. Belyakov ◽  
Lijuan Yang ◽  
Jay A. Berzofsky ◽  
Peter L. Collins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Type I Interferon ◽  
Human Respiratory Syncytial Virus ◽  
Interferon Response ◽  
Cytotoxic T Cell ◽  
Type I ◽  
Type I Ifn ◽  
Ifn Γ ◽  
Syncytial Virus

ABSTRACT The NS1 and NS2 proteins of human respiratory syncytial virus (HRSV) have been shown to antagonize the type I interferon (IFN) response, an effect subject to host range constraints. We have now found that the HRSV NS2 protein strongly controls IFN induction in mouse cells in vitro, validating the use of the mouse model to study the consequences of these gene deletions on host immunity. We evaluated the effects of deleting the NS1 and/or NS2 gene on the induction of HRSV-specific pulmonary cytotoxic T lymphocytes (CTL) in BALB/c and 129S6 mice in response to intranasal infection with HRSV lacking the NS1 and/or NS2 gene and subsequent challenge with wild-type (wt) HRSV. In mice infected with HRSV lacking the NS2 gene (ΔNS2) or lacking the NS2 gene in combination with the NS1 gene (ΔNS1/2 HRSV), the magnitude of the pulmonary CTL response was substantially elevated compared to that of mice infected with wt HRSV or the ΔNS1 mutant, whether measured by binding of CD8+ cells to an HRSV-specific major histocompatibility complex class I tetramer, by measurement of CD8+ cells secreting gamma interferon (IFN-γ) in response to specific in vitro stimulation, or by a standard chromium release cell-killing assay. In contrast, in STAT1 knockout mice, which lack responsiveness to type I IFN, the level of IFN-γ-secreting CD8+ cells was not significantly different for HRSV lacking the NS2 gene, suggesting that the increase in CTL observed in IFN-responsive mice is type I IFN dependent. Thus, the NS2 protein of HRSV suppresses the CTL component of the adaptive immune response, and this appears to be a consequence of its suppression of type I IFN.

scholarly journals Differential Role of Anti-Viral Sensing Pathway for the Production of Type I Interferon β in Dendritic Cells and Macrophages Against Respiratory Syncytial Virus A2 Strain Infection

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 62 ◽  
Author(s):  
Dong Oh ◽  
Tae Kim ◽  
Heung Lee
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Primary Response ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifns ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Mitochondrial Antiviral Signaling

Respiratory syncytial virus (RSV) is a major cause of respiratory infectious disease in infants and young children. Dendritic cells (DCs) and macrophages (MACs) are known to play important roles in RSV recognition, and in the production of type I interferons (IFNs) and pro-inflammatory cytokine in RSV infection. Toll-like receptor 7 (TLR7), myeloid differentiation primary response 88 (MyD88), and mitochondrial antiviral-signaling protein (MAVS) are known to be important for the RSV sensing pathway in DCs and MACs. However, despite the critical roles of type I IFNs in the anti-RSV immune response, the pattern recognition receptors (PRRs) that are required for RSV sensing in DCs and MACs remain unclear. Here, we investigate the pathway activated by RSV A2 strain infection using an IFN-β/YFP reporter mouse model to visualize IFN-β-producing cells and in vitro RSV infection in bone marrow-derived DCs (BM-DCs) and macrophages (BM-DMs). We present our finding that MyD88, but not TLR7, are important for RSV recognition and type I IFN and pro-inflammatory production in DCs and MACs. MAVS-deficient BM-DCs and BM-DMs show impaired induction of IFN-β production upon RSV stimulation, and this effect is RSV replication-dependent. Our study provides information on cell type-specific PRR requirements in innate immune responses against RSV infection.

scholarly journals Epitope mapping of human respiratory syncytial virus 22K transcription antitermination factor: role of N-terminal sequences in protein folding

2005 ◽  
Vol 86 (4) ◽  
pp. 1103-1107 ◽  
Author(s):  
Blanca García-Barreno ◽  
John Steel ◽  
Monica Payá ◽  
Luis Martínez-Sobrido ◽  
Teresa Delgado ◽  
...  
Keyword(s):  
Protein Folding ◽  
Respiratory Syncytial Virus ◽  
Western Blotting ◽  
Epitope Mapping ◽  
Human Respiratory Syncytial Virus ◽  
N Terminus ◽  
Transcription Antitermination ◽  
Syncytial Virus ◽  
Antibody Epitopes

The reactivity of a panel of 12 monoclonal antibodies raised against the human respiratory syncytial virus 22 kDa (22K) protein was tested by Western blotting with a set of 22K deletion mutants. The results obtained identified sequences in the C-terminal half of the 22K polypeptide required for integrity of most antibody epitopes, except for epitope 112, which was lost in mutants with short N-terminal deletions. This antibody, in contrast to the others, failed to immunoprecipitate the native 22K protein, indicating that the N terminus of this protein is buried in the native molecule and exposed only under the denaturing conditions of Western blotting. In addition, N-terminal deletions that abolished reactivity with monoclonal antibody 112 also inhibited phosphorylation of the 22K protein previously identified at Ser-58 and Ser-61, suggesting that the N terminus is important in regulating the 22K protein phosphorylation status, most likely as a result of its requirement for protein folding.

Platelets Modulate Innate Immune Response Against Human Respiratory Syncytial Virus In Vitro

2017 ◽  
Vol 30 (8) ◽  
pp. 576-581 ◽  
Author(s):  
Vesla I. Kullaya ◽  
Quirijn de Mast ◽  
Andre van der Ven ◽  
Hicham elMoussaoui ◽  
Gibson Kibiki ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Innate Immune Response ◽  
Human Respiratory Syncytial Virus ◽  
Innate Immune ◽  
Syncytial Virus

scholarly journals RAGE inhibits human respiratory syncytial virus syncytium formation by interfering with F-protein function

2013 ◽  
Vol 94 (8) ◽  
pp. 1691-1700 ◽  
Author(s):  
Jane Tian ◽  
Kelly Huang ◽  
Subramaniam Krishnan ◽  
Catherine Svabek ◽  
Daniel C. Rowe ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Syncytium Formation ◽  
Human Respiratory Syncytial Virus ◽  
Host Cells ◽  
Type I ◽  
F Protein ◽  
Viral Spread ◽  
Infected Cells ◽  
Syncytial Virus

Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection. Infection is critically dependent on the RSV fusion (F) protein, which mediates fusion between the viral envelope and airway epithelial cells. The F protein is also expressed on infected cells and is responsible for fusion of infected cells with adjacent cells, resulting in the formation of multinucleate syncytia. The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor that is constitutively highly expressed by type I alveolar epithelial cells. Here, we report that RAGE protected HEK cells from RSV-induced cell death and reduced viral titres in vitro. RAGE appeared to interact directly with the F protein, but, rather than inhibiting RSV entry into host cells, virus replication and budding, membrane-expressed RAGE or soluble RAGE blocked F-protein-mediated syncytium formation and sloughing. These data indicate that RAGE may contribute to protecting the lower airways from RSV by inhibiting the formation of syncytia, viral spread, epithelial damage and airway obstruction.

scholarly journals Mitoxantrone Shows In Vitro, but Not In Vivo Antiviral Activity against Human Respiratory Syncytial Virus

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1176
Author(s):  
Patricia G. de la Sota ◽  
Elena Lorente ◽  
Laura Notario ◽  
Carmen Mir ◽  
Oscar Zaragoza ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Infections ◽  
The Elderly ◽  
Human Respiratory Syncytial Virus ◽  
Mice Model ◽  
Drug Candidates ◽  
Antiviral Activities ◽  
Syncytial Virus

Human respiratory syncytial virus (HRSV) is the most common cause of severe respiratory infections in infants and young children, often leading to hospitalization. In addition, this virus poses a serious health risk in immunocompromised individuals and the elderly. HRSV is also a major nosocomial hazard in healthcare service units for patients of all ages. Therefore, the development of antiviral treatments against HRSV is a global health priority. In this study, mitoxantrone, a synthetic anthraquinone with previously reported in vitro antiprotozoal and antiviral activities, inhibits HRSV replication in vitro, but not in vivo in a mice model. These results have implications for preclinical studies of some drug candidates.

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