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 ◽  
...  

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.

2010 ◽  
Vol 84 (15) ◽  
pp. 7500-7512 ◽  
Author(s):  
Alfonsina Trento ◽  
Inmaculada Casas ◽  
Ana Calderón ◽  
Maria L. Garcia-Garcia ◽  
Cristina Calvo ◽  
...  

ABSTRACT The emergence of natural isolates of human respiratory syncytial virus group B (HRSV-B) with a 60-nucleotide (nt) duplication in the G protein gene in Buenos Aires, Argentina, in 1999 (A. Trento et al., J. Gen. Virol. 84:3115-3120, 2003) and their dissemination worldwide allowed us to use the duplicated segment as a natural tag to examine in detail the evolution of HRSV during propagation in its natural host. Viruses with the duplicated segment were all clustered in a new genotype, named BA (A. Trento et al., J. Virol. 80:975-984, 2006). To obtain information about the prevalence of these viruses in Spain, we tested for the presence of the duplicated segment in positive HRSV-B clinical samples collected at the Severo Ochoa Hospital (Madrid) during 12 consecutive epidemics (1996-1997 to 2007-2008). Viruses with the 60-nt duplication were found in 61 samples, with a high prevalence relative to the rest of B genotypes in the most recent seasons. Global phylogenetic and demographic analysis of all G sequences containing the duplication, collected across five continents up until April 2009, revealed that the prevalence of the BA genotype increased gradually until 2004-2005, despite its rapid dissemination worldwide. After that date and coinciding with a bottleneck effect on the population size, a relatively new BA lineage (BA-IV) replaced all other group B viruses, suggesting further adaptation of the BA genotype to its natural host.


2009 ◽  
Vol 5 (1) ◽  
pp. e1000254 ◽  
Author(s):  
Viviane F. Botosso ◽  
Paolo M. de A. Zanotto ◽  
Mirthes Ueda ◽  
Eurico Arruda ◽  
Alfredo E. Gilio ◽  
...  

2009 ◽  
Vol 83 (20) ◽  
pp. 10710-10718 ◽  
Author(s):  
Steven Kwilas ◽  
Rachael M. Liesman ◽  
Liqun Zhang ◽  
Edward Walsh ◽  
Raymond J. Pickles ◽  
...  

ABSTRACT Human respiratory syncytial virus (RSV) contains a heavily glycosylated 90-kDa attachment glycoprotein (G). Infection of HEp-2 and Vero cells in culture depends largely on virion G protein binding to cell surface glycosaminoglycans (GAGs). This GAG-dependent phenotype has been described for RSV grown in HEp-2 cells, but we have found that it is greatly reduced by a single passage in Vero cells. Virions produced from Vero cells primarily display a 55-kDa G glycoprotein. This smaller G protein represents a post-Golgi compartment form that is lacking its C terminus, indicating that the C terminus is required for GAG dependency. Vero cell-grown virus infected primary well-differentiated human airway epithelial (HAE) cell cultures 600-fold less efficiently than did HEp-2 cell-grown virus, indicating that the C terminus of the G protein is also required for virus attachment to this model of the in vivo target cells. This reduced infectivity for HAE cell cultures is not likely to be due to the loss of GAG attachment since heparan sulfate, the primary GAG used by RSV for attachment to HEp-2 cells, is not detectable at the apical surface of HAE cell cultures where RSV enters. Growing RSV stocks in Vero cells could dramatically reduce the initial infection of the respiratory tract in animal models or in volunteers receiving attenuated virus vaccines, thereby reducing the efficiency of infection or the efficacy of the vaccine.


2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Jie Yang ◽  
Chen Ma ◽  
Yu Zhao ◽  
Anjing Fan ◽  
Xiufen Zou ◽  
...  

ABSTRACT Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. The vaccine-enhanced disease (VED) has greatly hindered the development of an RSV vaccine. Currently, there are no licensed vaccines for RSV. In this study, immunization of mice with hepatitis B virus core particles containing a conserved region of the G protein (HBc-tG) combined with interleukin-35 (IL-35) elicited a Th1-biased response and a high frequency of regulatory T (Treg) cells and increased the levels of IL-10, transforming growth factor β, and IL-35 production. Importantly, immunization with HBc-tG together with IL-35 protected mice against RSV infection without vaccine-enhanced immunopathology. To explore the mechanism of how IL-35 reduces lung inflammation at the gene expression level, transcription profiles were obtained from lung tissues of immunized mice after RSV infection by the Illumina sequencing technique and further analyzed by a systems biology method. In total, 2,644 differentially expressed genes (DEGs) were identified. Twelve high-influence modules (HIMs) were selected from these DEGs on the basis of the protein-protein interaction network. A detailed analysis of HIM10, involved in the immune response network, revealed that Il10 plays a key role in regulating the host response. The selected DEGs were consistently confirmed by quantitative real-time PCR (qRT-PCR). Our results demonstrate that IL-35 inhibits vaccine-enhanced immunopathology after RSV infection and has potential for development in novel therapeutic and prophylactic strategies. IMPORTANCE In the past few decades, respiratory syncytial virus (RSV) has still been a major health concern worldwide. The vaccine-enhance disease (VED) has hindered RSV vaccine development. A truncated hepatitis B virus core protein vaccine containing the conserved region (amino acids 144 to 204) of the RSV G protein (HBc-tG) had previously been shown to induce effective immune responses and confer protection against RSV infection in mice but to also lead to VED. In this study, we investigated the effect of IL-35 on the host response and immunopathology following RSV infection in vaccinated mice. Our results indicate that HBc-tG together with IL-35 elicited a balanced immune response and protected mice against RSV infection without vaccine-enhanced immunopathology. Applying a systems biology method, we identified Il10 to be the key regulator in reducing the excessive lung inflammation. Our study provides new insight into the function of IL-35 and its regulatory mechanism of VED at the network level.


2015 ◽  
Vol 46 (5) ◽  
pp. 483-488 ◽  
Author(s):  
Wajihul Hasan Khan ◽  
V. L. N. Raghuram Srungaram ◽  
Asimul Islam ◽  
Ilyas Beg ◽  
Md. Shakir H. Haider ◽  
...  

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 ◽  
...  

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