scholarly journals Novel and extendable genotyping system for Human Respiratory Syncytial Virus based on whole-genome sequence analysis

Author(s):  
Jiani Chen ◽  
Xueting Qiu ◽  
Samuel Shepard ◽  
Do-Kyun Kim ◽  
James Hixson ◽  
...  

Background: Human respiratory syncytial virus (RSV) is one of the leading causes of respiratory infections, especially in infants and young children. Previous RSV sequencing studies have primarily focused on partial sequencing of G gene (200-300 nucleotides) for genotype characterization or diagnostics. However, the genotype assignment with G gene has not recapitulated the phylogenetic signal of other genes and there is no consensus on RSV genotype definition. Methods: We conducted Maximum Likelihood phylogenetic analysis with 10 RSV individual genes and whole-genome sequence (WGS) that are published in GenBank. RSV genotypes were assigned by the statistical support monophyletic clusters with at least 10-year detection time from the WGS phylogeny. Results: In this study, we first statistically examined the phylogenetic incongruence, rate variation for each RSV gene sequence and WGS. We then proposed a new RSV genotyping system based on a comparative analysis of WGS and the spatial and temporal distribution of each lineage. We also provided an RSV classification tool to perform RSV genotype assignment. Conclusions: This revised RSV genotyping system will provide important information for disease surveillance, epidemiology, and vaccine development.

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Kaat Ramaekers ◽  
Annabel Rector ◽  
Lize Cuypers ◽  
Philippe Lemey ◽  
Els Keyaerts ◽  
...  

Abstract Since the first human respiratory syncytial virus (HRSV) genotype classification in 1998, inconsistent conclusions have been drawn regarding the criteria that define HRSV genotypes and their nomenclature, challenging data comparisons between research groups. In this study, we aim to unify the field of HRSV genotype classification by reviewing the different methods that have been used in the past to define HRSV genotypes and by proposing a new classification procedure, based on well-established phylogenetic methods. All available complete HRSV genomes (>12,000 bp) were downloaded from GenBank and divided into the two subgroups: HRSV-A and HRSV-B. From whole-genome alignments, the regions that correspond to the open reading frame of the glycoprotein G and the second hypervariable region (HVR2) of the ectodomain were extracted. In the resulting partial alignments, the phylogenetic signal within each fragment was assessed. Maximum likelihood phylogenetic trees were reconstructed using the complete genome alignments. Patristic distances were calculated between all pairs of tips in the phylogenetic tree and summarized as a density plot in order to determine a cutoff value at the lowest point following the major distance peak. Our data show that neither the HVR2 fragment nor the G gene contains sufficient phylogenetic signal to perform reliable phylogenetic reconstruction. Therefore, whole-genome alignments were used to determine HRSV genotypes. We define a genotype using the following criteria: a bootstrap support of ≥70 per cent for the respective clade and a maximum patristic distance between all members of the clade of ≤0.018 substitutions per site for HRSV-A or ≤0.026 substitutions per site for HRSV-B. By applying this definition, we distinguish twenty-three genotypes within subtype HRSV-A and six genotypes within subtype HRSV-B. Applying the genotype criteria on subsampled data sets confirmed the robustness of the method.


2015 ◽  
Vol 89 (7) ◽  
pp. 3444-3454 ◽  
Author(s):  
Charles N. Agoti ◽  
James R. Otieno ◽  
Patrick K. Munywoki ◽  
Alexander G. Mwihuri ◽  
Patricia A. Cane ◽  
...  

ABSTRACTHuman respiratory syncytial virus (RSV) is associated with severe childhood respiratory infections. A clear description of local RSV molecular epidemiology, evolution, and transmission requires detailed sequence data and can inform new strategies for virus control and vaccine development. We have generated 27 complete or nearly complete genomes of RSV from hospitalized children attending a rural coastal district hospital in Kilifi, Kenya, over a 10-year period using a novel full-genome deep-sequencing process. Phylogenetic analysis of the new genomes demonstrated the existence and cocirculation of multiple genotypes in both RSV A and B groups in Kilifi. Comparison of local versus global strains demonstrated that most RSV A variants observed locally in Kilifi were also seen in other parts of the world, while the Kilifi RSV B genomes encoded a high degree of variation that was not observed in other parts of the world. The nucleotide substitution rates for the individual open reading frames (ORFs) were highest in the regions encoding the attachment (G) glycoprotein and the NS2 protein. The analysis of RSV full genomes, compared to subgenomic regions, provided more precise estimates of the RSV sequence changes and revealed important patterns of RSV genomic variation and global movement. The novel sequencing method and the new RSV genomic sequences reported here expand our knowledge base for large-scale RSV epidemiological and transmission studies.IMPORTANCEThe new RSV genomic sequences and the novel sequencing method reported here provide important data for understanding RSV transmission and vaccine development. Given the complex interplay between RSV A and RSV B infections, the existence of local RSV B evolution is an important factor in vaccine deployment.


2018 ◽  
Vol 6 (16) ◽  
pp. e00316-18 ◽  
Author(s):  
Amani Ezzeddine ◽  
Nadia Soudani ◽  
Chun Kiat Lee ◽  
Ghassan Dbaibo ◽  
Husni Elbahesh ◽  
...  

ABSTRACT We report here the complete genome sequence of a human respiratory syncytial virus (HRSV) strain obtained from an infant who presented to the emergency room with an acute respiratory illness during the 2014/2015 HRSV season in Lebanon. Analysis revealed that this virus belongs to the ON1 genotype that has recently emerged worldwide.


2010 ◽  
Vol 84 (16) ◽  
pp. 7970-7982 ◽  
Author(s):  
Margarita Magro ◽  
David Andreu ◽  
Paulino Gómez-Puertas ◽  
José A. Melero ◽  
Concepción Palomo

ABSTRACT Human respiratory syncytial virus (HRSV) fusion (F) protein is an essential component of the virus envelope that mediates fusion of the viral and cell membranes, and, therefore, it is an attractive target for drug and vaccine development. Our aim was to analyze the neutralizing mechanism of anti-F antibodies in comparison with other low-molecular-weight compounds targeted against the F molecule. It was found that neutralization by anti-F antibodies is related to epitope specificity. Thus, neutralizing and nonneutralizing antibodies could bind equally well to virions and remained bound after ultracentrifugation of the virus, but only the former inhibited virus infectivity. Neutralization by antibodies correlated with inhibition of cell-cell fusion in a syncytium formation assay, but not with inhibition of virus binding to cells. In contrast, a peptide (residues 478 to 516 of F protein [F478-516]) derived from the F protein heptad repeat B (HRB) or the organic compound BMS-433771 did not interfere with virus infectivity if incubated with virus before ultracentrifugation or during adsorption of virus to cells at 4°C. These inhibitors must be present during virus entry to effect HRSV neutralization. These results are best interpreted by asserting that neutralizing antibodies bind to the F protein in virions interfering with its activation for fusion. Binding of nonneutralizing antibodies is not enough to block this step. In contrast, the peptide F478-516 or BMS-433771 must bind to F protein intermediates generated during virus-cell membrane fusion, blocking further development of this process.


2015 ◽  
Vol 3 (5) ◽  
Author(s):  
Xuemin Fu ◽  
Yanwei Cheng ◽  
Zhixiang He ◽  
Wei Dong ◽  
Ke Lan ◽  
...  

We report here the complete genome sequence of human respiratory syncytial virus isolated from an outpatient child with fever and respiratory symptoms in Shanghai, China, in 2014. Phylogenetic analysis showed that the full-length respiratory syncytial virus (RSV) genome sequence belongs to human RSV (HRSV) group A.


PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e25468 ◽  
Author(s):  
Cecilia Rebuffo-Scheer ◽  
Michael Bose ◽  
Jie He ◽  
Shamim Khaja ◽  
Michael Ulatowski ◽  
...  

2016 ◽  
Vol 4 (1) ◽  
Author(s):  
J. E. Muñoz-Medina ◽  
I. E. Monroy-Muñoz ◽  
A. Santos Coy-Arechavaleta ◽  
A. Meza-Chávez ◽  
J. Ángeles-Martínez ◽  
...  

Human respiratory syncytial virus (HRSV) is a member of the Paramyxoviridae family, which causes lower respiratory tract infections in neonates and children younger than 5 years. Here, we report the complete genome sequence of HRSV, isolated from a nasopharyngeal swab of a pregnant woman with cardiac complications.


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