Molecular Evolution of Respiratory Syncytial Virus Fusion Gene, Canada, 2006–2010
Bibliographic record
Abstract
To assess molecular evolution of the respiratory syncytial virus (RSV) fusion gene, we analyzed RSVpositive specimens from 123 children in Canada who did or did not receive RSV immunoprophylaxis (palivizumab) during 2006-2010.Resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients.H uman respiratory syncytial virus (RSV) is the most common cause of acute respiratory tract infections (RTIs) and a major cause of hospital admission and death among children <5 years of age worldwide (1).Risk for severe RSV-associated illness is highest among children born prematurely or with chronic medical disorders (2).Palivizumab immunoprophylaxis is the only available measure to prevent severe RSV disease.The RSV fusion (RSV-F) surface glycoprotein mediates virus fusion to host cells.It is a major antigenic determinant that elicits neutralizing antibodies and cytotoxic T-lymphocyte immunity (3).Palivizumab (MedImmune, Gaithersburg, MD, USA) is a humanized mouse monoclonal antibody that inhibits RSV-F by binding to a defi ned epitope (residues 262-276) (4,5).Palivizumab immunoprophylaxis is recommended for the prevention of serious lower RTIs caused by RSV in children at high risk (6).RSV strains with mutations in key amino acid residues within the palivizumab binding site are resistant to this antibody (7-9); however, little is known about the prevalence of such mutations in clinical samples.Furthermore, despite its role in RSV pathogenesis, immunity, and prevention strategies, few data on RSV-F molecular evolution are available (10,11) because previous phylogenetic studies have focused on the RSV-G glycoprotein (12,13).Therefore, we monitored evolutionary changes in RSV-F, particularly potential resistance mutations in the palivizumab binding site, among strains from children who did and did not receive palivizumab. The StudyThis cohort study was approved by the Centre Hospitalier Universitaire de Québec Research Ethics Board.Participants were <3 years of age and either received medical attention at an outpatient pediatric clinic or were hospitalized at a pediatric center for acute RTI during 4 winter seasons (2006)(2007)(2008)(2009)(2010), in Québec City, Québec, Canada.Clinical data were prospectively collected at study entry and after 1-month follow-up.For all patients, at the fi rst visit a nasopharyngeal aspirate was collected.The aspirate was frozen at -80°C until subsequent testing by a multiplex PCR/DNA hybridization assay that detects RSV genotype-A (RSV-A), RSV-B, and 22 other respiratory viruses (Infi niti RVP assay; Autogenomics, Carlsbad, CA, USA) (14).RSV infection was identifi ed in aspirates from 467 (63.6%) of 734 hospitalized children (257 RSV-A, 210 RSV-B) and from 147 (48.2%) of 305 outpatient children (85 RSV-A, 62 RSV-B).During 2006-2010, a total of 724 children received palivizumab in the Québec City region (L.Cliche, pers.comm.).RSV-positive samples from all 12 study participants receiving palivizumab and from 100 not receiving palivizumab underwent RSV-F sequencing.Additionally, F-gene analysis was performed on 11 RSV-positive clinical samples from palivizumab recipients retrospectively identifi ed by using neonatal clinic registries at McMaster Children's Hospital (Hamilton, Ontario, Canada) and Montréal Children's Hospital (Montréal, Québec, Canada) during 2009-2010.Clinical data were collected by chart review.RNA was extracted directly from nasopharyngeal samples by using a QIAmp Viral RNA Mini Kit (QIAGEN, Mississauga, Ontario, Canada).Random primers (Amersham, Piscataway, NJ, USA) and Superscript II RT Kit (Invitrogen, Carlsbad, CA, USA) were used for reverse transcription.PCR amplifi cation was performed with QuantiFast Probe PCR+ROX Vial Kit (QIAGEN); primers and thermocycling conditions are available from G.B. upon request.RSV-F amplicons were sequenced by using an automated sequencer (
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".