High epidemic burden of RSV disease coinciding with genetic alterations causing amino acid substitutions in the RSV G-protein during the 2016/2017 season in The Netherlands

Vos, Laura M.; Oosterheert, Jan Jelrik; Kuil, Sacha D.; Viveen, Marco C.; Bont, Louis; Hoepelman, Andy I. M.; Coenjaerts, Frank E. J.

doi:10.1016/j.jcv.2019.01.007

Cited by 20 publications

(21 citation statements)

References 22 publications

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“…The alignment of the predicted amino acid sequences of strains from BA9, NA1 and ON1 genotypes confirmed the relatively high genetic variability associated with the HVR2. Strains from both of subtypes showed common changes, conserved N-glycosilation sites and subtitutions leading to loss or gain of these sites that had been previously reported [11,40,41,45,46,49,50,[54][55][56][57][58][59]. Within RSV-A strains, the number of substitutions among ON1 strains was higher compared with its NA1 counterparts.…”

Section: Discussionsupporting

confidence: 59%

“…RSV-A subtype was significantly higher in children younger than 5 years and especially those aged below 6 months, which may be concerning since RSV-A infection has been associated with more severe bronchiolitis and higher disease severity scores [43,44]. However, discrepancies have been described [45], and indeed, specific substitutions may indicate the most virulent strains during a specific period of time better than the subtype [46]. RSV-B subtype was significantly higher in 15-44 years old and female patients.…”

Section: Discussionmentioning

confidence: 99%

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Epidemiology and genetic variability of respiratory syncytial virus in Portugal, 2014–2018

Sáez-López

Cristóvão

Costa

et al. 2019

Journal of Clinical Virology

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A B S T R A C TIntroduction: Respiratory syncytial virus (RSV) is associated with substantial morbidity and mortality since it is a predominant viral agent causing respiratory tract infections in infants, young children and the elderly. Considering the availability of the RSV vaccines in the coming years, molecular understanding in RSV is necessary. Objective: The objective of the present study was to describe RSV epidemiology and genotype variability in Portugal during the 2014/15-2017/18 period. Material and methods: Epidemiological data and RSV-positive samples from patients with a respiratory infection were collected through the non-sentinel and sentinel influenza surveillance system (ISS). RSV detection, subtyping in A and B, and sequencing of the second hypervariable region (HVR2) of G gene were performed by molecular methods. Phylogenetic trees were generated using the Neighbor-Joining method and p-distance model on MEGA 7.0. Results: RSV prevalence varied between the sentinel (2.5%, 97/3891) and the non-sentinel ISS (20.7%, 3138/ 16779), being higher (P < 0.0001) among children aged < 5 years. Bronchiolitis (62.9%, 183/291) and influenza-like illness (24.6%, 14/57) were associated (P < 0.0001) with RSV laboratory confirmation among children aged < 6 months and adults ≥65 years, respectively. The HVR2 was sequenced for 562 samples. RSV-A (46.4%, 261/562) and RSV-B (53.6%, 301/562) strains clustered mainly to ON1 (89.2%, 233/261) and BA9

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Epidemiology and genetic variability of respiratory syncytial virus in Portugal, 2014–2018

Sáez-López

Cristóvão

Costa

et al. 2019

Journal of Clinical Virology

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“…Studies in mice show strain-specific differences in virulence associated with sequences in the F protein gene [ 61 , 62 ]. In a recent study, investigators from the Netherlands looked at G gene sequences and their data suggest that specific amino acid changes are associated with increased disease severity [ 63 ]. Such links between G gene sequences and disease severity, however, need to be confirmed.…”

Section: Structure Of Gmentioning

confidence: 99%

Functional Features of the Respiratory Syncytial Virus G Protein

Anderson

Jadhao

Paden

et al. 2021

Viruses

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Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in children <5 years of age worldwide and repeated infections throughout life leading to serious disease in the elderly and persons with compromised immune, cardiac, and pulmonary systems. The disease burden has made it a high priority for vaccine and antiviral drug development but without success except for immune prophylaxis for certain young infants. Two RSV proteins are associated with protection, F and G, and F is most often pursued for vaccine and antiviral drug development. Several features of the G protein suggest it could also be an important to vaccine or antiviral drug target design. We review features of G that effect biology of infection, the host immune response, and disease associated with infection. Though it is not clear how to fit these together into an integrated picture, it is clear that G mediates cell surface binding and facilitates cellular infection, modulates host responses that affect both immunity and disease, and its CX3C aa motif contributes to many of these effects. These features of G and the ability to block the effects with antibody, suggest G has substantial potential in vaccine and antiviral drug design.

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“…The authors suggested to use a system based on the H5N1 influenza virus classification approach of WHO, in which clade names would be derived from the names of the genotype they originate from. Additionally, clades would be defined based on BS values of 60 per cent or higher and with an average genetic distance of at least 1.5 per cent to other clades and <1.5 per cent within the clade ( WHO/OIE/FAO H5N1 Evolution Working Group 2008 ; Agoti et al. 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Towards a unified classification for human respiratory syncytial virus genotypes

et al. 2020

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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 base pairs) 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 cut-off value at the lowest point following the major distance peak. Our data shows 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% 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 23 genotypes within subtype HRSV-A and six genotypes within subtype HRSV-B. Applying the genotype criteria on subsampled datasets confirmed the robustness of the method.

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High epidemic burden of RSV disease coinciding with genetic alterations causing amino acid substitutions in the RSV G-protein during the 2016/2017 season in The Netherlands

Cited by 20 publications

References 22 publications

Epidemiology and genetic variability of respiratory syncytial virus in Portugal, 2014–2018

Epidemiology and genetic variability of respiratory syncytial virus in Portugal, 2014–2018

Functional Features of the Respiratory Syncytial Virus G Protein

Towards a unified classification for human respiratory syncytial virus genotypes

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