scholarly journals Immunogenicity and inflammatory properties of respiratory syncytial virus attachment G protein in cotton rats

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246770
Author(s):  
Margaret E. Martinez ◽  
Cristina Capella Gonzalez ◽  
Devra Huey ◽  
Mark E. Peeples ◽  
Douglas McCarty ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Neutralizing Antibodies ◽  
Protein Gene ◽  
Pulmonary Inflammation ◽  
Vector System ◽  
Interferon Α ◽  
Cotton Rat ◽  
Membrane Bound ◽  
Syncytial Virus

Human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants and young children worldwide. The attachment (G) protein of RSV is synthesized by infected cells in both a membrane bound (mG) and secreted form (sG) and uses a CX3C motif for binding to its cellular receptor. Cell culture and mouse studies suggest that the G protein mimics the cytokine CX3CL1 by binding to CX3CR1 on immune cells, which is thought to cause increased pulmonary inflammation in vivo. However, because these studies have used RSV lacking its G protein gene or blockade of the G protein with a G protein specific monoclonal antibody, the observed reduction in inflammation may be due to reduced virus replication and spread, and not to a direct role for G protein as a viral chemokine. In order to more directly determine the influence of the soluble and the membrane-bound forms of G protein on the immune system independent of its attachment function for the virion, we expressed the G protein in cotton rat lungs using adeno-associated virus (AAV), a vector system which does not itself induce inflammation. We found no increase in pulmonary inflammation as determined by histology and bronchoalveolar lavage after inoculation of AAVs expressing the membrane bound G protein, the secreted G protein or the complete G protein gene which expresses both forms. The long-term low-level expression of AAV-G did, however, result in the induction of non-neutralizing antibodies, CD8 T cells and partial protection from challenge with RSV. Complete protection was accomplished through co-immunization with AAV-G and an AAV expressing cotton rat interferon α.

scholarly journals Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus

2009 ◽  
Vol 5 (1) ◽  
pp. e1000254 ◽  
Author(s):  
Viviane F. Botosso ◽  
Paolo M. de A. Zanotto ◽  
Mirthes Ueda ◽  
Eurico Arruda ◽  
Alfredo E. Gilio ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Amino Acid ◽  
Positive Selection ◽  
G Protein ◽  
Protein Gene ◽  
Human Respiratory Syncytial Virus ◽  
Syncytial Virus

scholarly journals Prophylactic Treatment with a G Glycoprotein Monoclonal Antibody Reduces Pulmonary Inflammation in Respiratory Syncytial Virus (RSV)-Challenged Naïve and Formalin-Inactivated RSV-Immunized BALB/c Mice

2010 ◽  
Vol 84 (18) ◽  
pp. 9632-9636 ◽  
Author(s):  
Gertrud U. Radu ◽  
Hayat Caidi ◽  
Congrong Miao ◽  
Ralph A. Tripp ◽  
Larry J. Anderson ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Respiratory Syncytial Virus ◽  
Inflammatory Response ◽  
G Protein ◽  
Primary Infection ◽  
Prophylactic Treatment ◽  
Pulmonary Inflammation ◽  
Rsv Infection ◽  
Pulmonary Inflammatory Response ◽  
Syncytial Virus

ABSTRACT We examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated RSV (FI-RSV)-enhanced disease in mice. MAb 131-2G administration 1 day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab′)2 forms of MAb 131-2G administered 1 day prior to infection in FI-RSV-vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein MAb might provide prophylaxis against both primary infection and FI-RSV-associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines.

scholarly journals Intrapatient Variation of the Respiratory Syncytial Virus Attachment Protein Gene

2010 ◽  
Vol 84 (19) ◽  
pp. 10425-10428 ◽  
Author(s):  
Charles N. Agoti ◽  
Jean L. Mbisa ◽  
Ann Bett ◽  
Graham F. Medley ◽  
D. James Nokes ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Protein Gene ◽  
Point Mutations ◽  
Virus Attachment ◽  
Single Genome ◽  
B Virus ◽  
Intrapatient Variability ◽  
Syncytial Virus ◽  
Group B

ABSTRACT Intrapatient variability of the attachment (G) protein gene of respiratory syncytial virus (RSV) was examined using both population and single-genome sequencing. Samples from three patients infected with a group B virus variant which has a 60-nucleotide duplication in the G protein gene were examined. These samples were chosen because occasional mixed sequence bases were observed. In a minority of RSV genomes from these patients considerable variability was found, including point mutations, insertions, and deletions. Of particular note, the deletion of the exact portion of the gene which had been duplicated in some isolates was observed in viral RNAs from two patients.

scholarly journals Nonglycosylated G-Protein Vaccine Protects against Homologous and Heterologous Respiratory Syncytial Virus (RSV) Challenge, while Glycosylated G Enhances RSV Lung Pathology and Cytokine Levels

2015 ◽  
Vol 89 (16) ◽  
pp. 8193-8205 ◽  
Author(s):  
Sandra Fuentes ◽  
Elizabeth M. Coyle ◽  
Hana Golding ◽  
Surender Khurana
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Mammalian Cells ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Lung Pathology ◽  
Content Type ◽  
Viral Loads ◽  
Syncytial Virus

ABSTRACTNew efforts are under way to develop a vaccine against respiratory syncytial virus (RSV) that will provide protective immunity without the potential for vaccine-associated disease enhancement such as that observed in infants following vaccination with formalin-inactivated RSV vaccine. In addition to the F fusion protein, the G attachment surface protein is a target for neutralizing antibodies and thus represents an important vaccine candidate. However, glycosylated G protein expressed in mammalian cells has been shown to induce pulmonary eosinophilia upon RSV infection in a mouse model. In the current study, we evaluated in parallel the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain (amino acids 67 to 298) expressed inEscherichia coli(REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model. Vaccination with REG generated neutralizing antibodies against RSV A2 in 7/11 BALB/c mice, while RMG did not elicit neutralizing antibodies. Total serum binding antibodies against the recombinant proteins (both REG and RMG) were measured by surface plasmon resonance (SPR) and were found to be >10-fold higher for REG- than for RMG-vaccinated animals. Reduction of lung viral loads to undetectable levels after homologous (RSV-A2) and heterologous (RSV-B1) viral challenge was observed in 7/8 animals vaccinated with REG but not in RMG-vaccinated animals. Furthermore, enhanced lung pathology and elevated Th2 cytokines/chemokines were observed exclusively in animals vaccinated with RMG (but not in those vaccinated with REG or phosphate-buffered saline [PBS]) after homologous or heterologous RSV challenge. This study suggests that bacterially produced unglycosylated G protein could be developed alone or as a component of a protective vaccine against RSV disease.IMPORTANCENew efforts are under way to develop vaccines against RSV that will provide protective immunity without the potential for disease enhancement. The G attachment protein represents an important candidate for inclusion in an effective RSV vaccine. In the current study, we evaluated the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain produced inE. coli(REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model (strains A2 and B1). The unglycosylated G generated high protective immunity and no lung pathology, even in animals that lacked anti-RSV neutralizing antibodies prior to RSV challenge. Control of viral loads correlated with antibody binding to the G protein. In contrast, the glycosylated G protein provided poor protection and enhanced lung pathology after RSV challenge. Therefore, bacterially produced unglycosylated G protein holds promise as an economical approach to a protective vaccine against RSV.

Genetic variability in the G protein gene of human respiratory syncytial virus isolated from the Campinas metropolitan region, Brazil

2008 ◽  
Vol 80 (9) ◽  
pp. 1653-1660 ◽  
Author(s):  
Luciana Helena Antoniassi da Silva ◽  
Fernando Rosado Spilki ◽  
Adriana Gut Lopes Riccetto ◽  
Renata Servan de Almeida ◽  
Emílio Carlos Elias Baracat ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Genetic Variability ◽  
G Protein ◽  
Protein Gene ◽  
Human Respiratory Syncytial Virus ◽  
Metropolitan Region ◽  
Syncytial Virus

scholarly journals Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus G Protein Induced Protection in BALB/c Mice, with No Evidence of Immunopathology

2009 ◽  
Vol 84 (2) ◽  
pp. 1110-1123 ◽  
Author(s):  
Matthew R. Murawski ◽  
Lori W. McGinnes ◽  
Robert W. Finberg ◽  
Evelyn A. Kurt-Jones ◽  
Michael J. Massare ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Newcastle Disease Virus ◽  
G Protein ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Neutralizing Antibodies ◽  
Respiratory Infections ◽  
Chimeric Protein ◽  
Virus Like Particle ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of serious respiratory infections in children as well as a serious cause of disease in elderly and immunosuppressed populations. There are no licensed vaccines available to prevent RSV disease. We have developed a virus-like particle (VLP) vaccine candidate for protection from RSV. The VLP is composed of the NP and M proteins of Newcastle disease virus (NDV) and a chimeric protein containing the cytoplasmic and transmembrane domains of the NDV HN protein and the ectodomain of the human RSV G protein (H/G). Immunization of mice with 10 or 40 μg total VLP-H/G protein by intraperitoneal or intramuscular inoculation stimulated antibody responses to G protein which were as good as or better than those stimulated by comparable amounts of UV-inactivated RSV. Immunization of mice with two doses or even a single dose of these particles resulted in the complete protection of mice from RSV replication in the lungs. Immunization with these particles induced neutralizing antibodies with modest titers. Upon RSV challenge of VLP-H/G-immunized mice, no enhanced pathology in the lungs was observed, although lungs of mice immunized in parallel with formalin-inactivated RSV (FI-RSV) showed the significant pathology that has previously been documented after immunization with FI-RSV. Thus, the VLP-H/G candidate vaccine was immunogenic in BALB/c mice and prevented replication of RSV in murine lungs, with no evidence of immunopathology. These data support further development of virus-like particle vaccine candidates for protection against RSV.

Nosocomial outbreak of respiratory syncytial virus subgroup B variants with the 60 nucleotides-duplicated G protein gene

2004 ◽  
Vol 74 (1) ◽  
pp. 161-165 ◽  
Author(s):  
Kazushige Nagai ◽  
Hotaka Kamasaki ◽  
Yuki Kuroiwa ◽  
Lisa Okita ◽  
Hiroyuki Tsutsumi
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Protein Gene ◽  
Nosocomial Outbreak ◽  
Syncytial Virus

scholarly journals The antigenic and genetic variability of bovine respiratory syncytial virus with emphasis on the G protein

2012 ◽  
Vol 48 (No. 9) ◽  
pp. 254-266 ◽  
Author(s):  
V. Valentova
Keyword(s):  
Respiratory Syncytial Virus ◽  
Genetic Variability ◽  
G Protein ◽  
Viral Protein ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Clinical Symptoms ◽  
Bovine Respiratory Syncytial Virus ◽  
Th2 Response ◽  
Syncytial Virus

Bovine respiratory syncytial virus (BRSV) and related human respiratory syncytial virus (HRSV) are major respiratory tract pathogens in calves and infants, respectively. Great attention is now paid to prevention of the disease caused by these agents. Glycoprotein G is the most variable viral protein and antigenic grouping of RSV isolates is based on distinct antigenic reactivity patterns determined with a set of G protein specific mAbs. Genetic variability of the G protein is used during epidemiology and epizootiology studies of HRSV and BRSV diseases, respectively. The constant genetic drift can be observed within G protein sequences. Both cell-mediated and antibody-mediated immune responses contribute to efficient protection against RSV infection. The neutralizing antibodies are induced by F and G proteins. The G protein fails to induce cytotoxic lymphocytes response and may causes aberrant Th2 response leading to enhancement of clinical symptoms in subsequently infected vaccines. The G as the most variable viral protein associated with immunopathologic effect is a critical factor in vaccine development.

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