Immunological Characterization of Respiratory Syncytial Virus N Protein Epitopes Recognized by Human Cytotoxic T Lymphocytes

2007 ◽  
Vol 20 (3) ◽  
pp. 399-406 ◽  
Author(s):  
Chiara Terrosi ◽  
Giuseppa Di Genova ◽  
Gianni Gori Savellini ◽  
Pierpaolo Correale ◽  
Patrizia Blardi ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Immunological Characterization ◽  
N Protein ◽  
Syncytial Virus

scholarly journals Alternative Mechanisms of Respiratory Syncytial Virus Clearance in Perforin Knockout Mice Lead to Enhanced Disease

2001 ◽  
Vol 75 (20) ◽  
pp. 9918-9924 ◽  
Author(s):  
Sandra Aung ◽  
John A. Rutigliano ◽  
Barney S. Graham
Keyword(s):  
Respiratory Syncytial Virus ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Cell Lysis ◽  
Target Cells ◽  
Alternative Mechanism ◽  
Wild Type ◽  
Infected Cells ◽  
Syncytial Virus

ABSTRACT Virus-specific cytotoxic T lymphocytes are key effectors for the clearance of virus-infected cells and are required for the normal clearance of respiratory syncytial virus (RSV) in mice. Although perforin/granzyme-mediated lysis of infected cells is thought to be the major molecular mechanism used by CD8+ cytotoxic T lymphocytes for elimination of virus, its role in RSV has not been reported. Here, we show that viral clearance in perforin knockout (PKO) mice is slightly delayed but that both PKO and wild-type mice clear virus by day 10, suggesting an alternative mechanism of RSV clearance. Effector T cells from the lungs of both groups of mice were shown to lyse Fas (CD95)-overexpressing target cells in greater numbers than target cells expressing low levels of Fas, suggesting that Fas ligand (CD95L)-mediated target cell lysis was occurring in vivo. This cell lysis was associated with a delay in RSV-induced disease in PKO mice compared to the time of disease onset for wild-type controls, which correlated with increased and prolonged production of gamma interferon and tumor necrosis factor alpha levels in PKO mice. We conclude that while perforin is not necessary for the clearance of primary RSV infection, the use of alternative CTL target cell killing mechanisms is less efficient and can lead to enhanced disease.

Characterization of novel respiratory syncytial virus inhibitors identified by high throughput screen

2015 ◽  
Vol 115 ◽  
pp. 71-74 ◽  
Author(s):  
Valerie A. Laganas ◽  
Ewan F. Dunn ◽  
Robert E. McLaughlin ◽  
Choi Lai Tiong-Yip ◽  
Olga Yuzhakov ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
High Throughput ◽  
High Throughput Screen ◽  
Syncytial Virus

scholarly journals Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation

2017 ◽  
Vol 91 (13) ◽  
Author(s):  
Normand Blais ◽  
Martin Gagné ◽  
Yoshitomo Hamuro ◽  
Patrick Rheault ◽  
Martine Boyer ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Human Respiratory Syncytial Virus ◽  
Vaccine Antigen ◽  
Significant Advance ◽  
F Protein ◽  
Syncytial Virus

ABSTRACT The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen. IMPORTANCE Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F) glycoprotein is considered one of the most promising vaccine candidates, and recent evidences suggest that the prefusion (pre-F) state is a superior target for neutralizing antibodies. Our study presents the physicochemical characterization of Pre-F-GCN4t, a molecule designed to be stabilized in the pre-F conformation. To confirm its pre-F conformation, Pre-F-GCN4t was analyzed in parallel with Post-F-XC, a molecule in the post-F conformation. Our results show that Pre-F-GCN4t presents characteristics of a stabilized pre-F conformation and support its use as an RSV vaccine antigen. Such an antigen may represent a significant advance in the development of an RSV vaccine.

Design and characterization of a fusion glycoprotein vaccine for Respiratory Syncytial Virus with improved stability

Vaccine ◽  
2018 ◽  
Vol 36 (52) ◽  
pp. 8119-8130 ◽  
Author(s):  
Lan Zhang ◽  
Eberhard Durr ◽  
Jennifer D. Galli ◽  
Scott Cosmi ◽  
Pedro J. Cejas ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Fusion Glycoprotein ◽  
Improved Stability ◽  
Syncytial Virus

Molecular characterization of HLA-C incompatibilities recognised by alloreactive cytotoxic T lymphocytes

1996 ◽  
Vol 47 (1-2) ◽  
pp. 81
Author(s):  
Grundschober Christophe ◽  
Rufer Nathalie ◽  
Jeannet Michel ◽  
Roosnek Eddy ◽  
Tiercy Jean-Marie
Keyword(s):  
T Lymphocytes ◽  
Molecular Characterization ◽  
Cytotoxic T Lymphocytes
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