Immune responses to the nonglycosylated ectodomain of respiratory syncytial virus attachment glycoprotein mediate pulmonary eosinophilia in inbred strains of mice with different MHC haplotypes

Hancock, Gerald E.; Tebbey, Paul W.; Scheuer, Catherine A.; Pryharski, Karin S.; Heers, Kristen M.; LaPierre, Natisha A.

doi:10.1002/jmv.10395

Cited by 29 publications

(22 citation statements)

References 36 publications

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“…Alternatively, secondary epitopes outside the central ectodomain may yield type 2 T-cell responses against G protein that result in eosinophilia. Previous studies (24,48,55) …”

Section: Discussionmentioning

confidence: 94%

“…Our strategy was based on results from studies that indicated that PBMC from most adult human donors were readily activated upon stimulation with peptide antigens from the region of G protein spanned by amino acids 149 to 200 (20). It was further demonstrated that epitopes within the region primed several inbred strains of mice for pulmonary eosinophilia (24). At first, it was not clear what impact genetic alteration of this magnitude would have on attenuation, immunogenicity, and pulmonary eosinophilia.…”

Section: Discussionmentioning

confidence: 99%

“…The recall responses of T cells from mice (24) and humans (20) against G protein appear to be directed primarily against epitopes within the ectodomain encompassed by amino acids 149 to 200. To diminish T-cell responses to G protein and improve safety, antigenomic cDNAs with deletions of nucleotides in this region were constructed (Fig.…”

Section: Construction Of Rrsv Strains With Altered G Proteinmentioning

confidence: 99%

“…Recently it was reported that PBMC from most human volunteers readily recognized epitopes located within the central ectodomain encompassed by amino acids 149 to 200 of G protein (20). A synthetic peptide composed of amino acids 149 to 200 and conjugated to a carrier primed several strains of inbred mice for pulmonary eosinophilia (24). The results presented here describe efforts to construct rRSV strains in which the region likely to induce unbalanced T-cell responses against G protein is deleted.…”

mentioning

confidence: 95%

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Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Elliott¹,

Pryharski²,

et al. 2004

J Virol

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It is essential that preventative vaccines for respiratory syncytial virus (RSV) elicit balanced T-cell responses. Immune responses dominated by type 2 T cells against RSV antigens are believed to cause exaggerated respiratory tract disease and may also contribute to unwanted inflammation in the airways that predisposes infants to wheeze through adolescence. Here we report on the construction and characterization of recombinant RSV (rRSV) strains with amino acids 151 to 221 or 178 to 219 of the attachment (G) glycoprotein deleted (rA2cp⌬G150-222 or rA2cp⌬G177-220, respectively). The central ectodomain was chosen for modification because a peptide spanning amino acids 149 to 200 of G protein has recently been shown to prime several strains of naïve inbred mice for polarized type 2 T-cell responses, and peripheral blood T cells from most human donors recognize epitopes within this region. Quantitative PCR demonstrated that synthesis of nascent rRSV genomes in human lung epithelial cell lines was similar to that for the parent virus (cp-RSV). Plaque assays further indicated that rRSV replication was not sensitive to 37°C, but pinpoint morphology was observed at 39°C. Both rRSV strains replicated in the respiratory tracts of BALB/c mice and elicited serum neutralization and anti-F-protein immunoglobulin G titers that were equivalent to those elicited by cp-RSV and contributed to a 3.9-log 10 -unit reduction in RSV A2 levels 4 days after challenge. Importantly, pulmonary eosinophilia was significantly diminished in BALB/c mice primed with native G protein and challenged with either rA2cp⌬G150-222 or rA2cp⌬G177-220. These findings are important for the development of attenuated RSV vaccines.

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“…Alternatively, secondary epitopes outside the central ectodomain may yield type 2 T-cell responses against G protein that result in eosinophilia. Previous studies (24,48,55) …”

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Construction Of Rrsv Strains With Altered G Proteinmentioning

confidence: 99%

mentioning

confidence: 95%

See 2 more Smart Citations

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Elliott¹,

Pryharski²,

et al. 2004

J Virol

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“…Pulmonary eosinophilia also occurs after RSV challenge of BALB/c mice previously immunized with a recombinant vaccinia virus (vacv) expressing the attachment (G) protein of RSV (vacvG) [32][33][34][35][36]. Similar to the memory T cell response induced following FI-RSV immunization, the memory T cell response to the G protein consists of CD4 but not CD8 T cells [37][38][39].…”

Section: The Contribution Of Memory Cd4 T Cells To Rsv Vaccine-enhancmentioning

confidence: 99%

Overcoming T-Cell-Mediated Immunopathology to Achieve Safe Respiratory Syncytial Virus Vaccination

Castilow

Varga

2008

Future Virol.

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SummaryRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in young children. Premature infants, immunocompromised individuals, and the elderly exhibit an increased risk for the development of severe disease after RSV infection. Currently, there is not a safe and effective RSV vaccine available, in part due to our incomplete understanding of how severe immunopathology was induced following RSV infection of children previously immunized with a formalin-inactivated RSV vaccine. Much of our current understanding of RSV vaccine-enhanced disease can be attributed to the establishment of multiple mouse models of RSV vaccination. Studies analyzing the RSV-specific immune response in mice have clearly demonstrated that both CD4 and CD8 memory T cells contribute to RSV-induced immunopathology. In this review we will focus our discussion on data generated from the mouse models of RSV immunization that have advanced our understanding of how virus-specific T cells mediate immunopathology and RSV vaccine-enhanced disease.

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Molecular epidemiology of human respiratory syncytial virus over three consecutive seasons in Latvia

Balmaks

Ribakova

Gardovska

et al. 2013

Journal of Medical Virology

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Lower respiratory tract infections caused by the human respiratory syncytial virus (HRSV) represent an immense burden of the disease, especially in young children. This study aimed to investigate the evolutionary history of HRSV strains isolated in the Children's Clinical University Hospital (Riga, Latvia) over three consecutive HRSV seasons. Of 207 samples from children hospitalized with lower respiratory tract infections, 88 (42.5%) tested positive for HRSV by RT‐PCR. The seasonal activity started and peaked later than the average for the Northern hemisphere. Patients with HRSV lower respiratory tract infection were significantly younger than patients not infected with HRSV. HRSV‐A viruses predominated for two consecutive seasons and were followed by an HRSV‐B dominant season. Phylogenetic analysis based on glycoprotein G gene partial sequences revealed that viruses of both groups belonged to the worldwide dominant genotypes NA1 (HRSV‐A) and BA‐IV (HRSV‐B). High diversity of this gene was driven only partially by selection pressure, as only two positively selected sites were identified in each group. Two of the HRSV‐A isolates in this study contained a 72‐nt duplication in the C‐terminal end of the G gene (genotype ON1) that was first described in Canada in the 2010–2011 season. Initial spatial and temporal dynamics of this novel genotype were reconstructed by discrete phylogeographic analysis. Fifteen years after acquiring comparable 60‐nt duplication in the G gene, genotype BA lineages have replaced all other HRSV‐B strains. However, the population size of genotype ON1 plateaued soon and even decreased slightly before the beginning of the 2012–2013 season. J. Med. Virol. 86:1971–1982, 2014. © 2013 Wiley Periodicals, Inc.

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Immune responses to the nonglycosylated ectodomain of respiratory syncytial virus attachment glycoprotein mediate pulmonary eosinophilia in inbred strains of mice with different MHC haplotypes

Cited by 29 publications

References 36 publications

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Overcoming T-Cell-Mediated Immunopathology to Achieve Safe Respiratory Syncytial Virus Vaccination

Molecular epidemiology of human respiratory syncytial virus over three consecutive seasons in Latvia

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