Genetic Variability of Human Respiratory Syncytial Virus A Strains Circulating in Ontario A Novel Genotype with a 72 Nucleotide G Gene Duplication 英文参考文献.docVIP

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Genetic Variability of Human Respiratory Syncytial Virus A Strains Circulating in Ontario A Novel Genotype with a 72 Nucleotide G Gene Duplication 英文参考文献.doc

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Genetic Variability of Human Respiratory Syncytial Virus A Strains Circulating in Ontario A Novel Genotype with a 72 Nucleotide G Gene Duplication 英文参考文献

GeneticVariabilityofHumanRespiratorySyncytialVirus AStrainsCirculatinginOntario:ANovelGenotypewitha 72NucleotideGGeneDuplication AliRezaEshaghi1,VenkataR.Duvvuri1,2,RachelLai1,JeyaT.Nadarajah3,AiminLi1,SamirN.Patel1, DonaldE.Low1,2,3,JonathanB.Gubbay1,2,3,4 * 1Ontario Agencyfor Health Protection and Promotion, Toronto, Ontario,Canada,2Mount Sinai Hospital, Toronto,Ontario, Canada, 3UniversityofToronto,Toronto, Ontario,Canada,4TheHospitalforSickChildren,Toronto,Ontario,Canada Abstract Humanrespiratorysyncytialvirus(HRSV)isthemaincauseofacutelowerrespiratoryinfectionsinchildrenunder2yearsof ageandcausesrepeatedinfectionsthroughoutlife.WeinvestigatedthegeneticvariabilityofRSV-AcirculatinginOntario during2010–2011winterseasonbysequencingandphylogeneticanalysisoftheGglycoproteingene. Amongthe201 consecutive RSV isolates studied, RSV-A (55.7%) was more commonly observed than RSV-B (42.3%). 59.8% and90.1% of RSV-Ainfectionswereamongchildren#12monthsand#5yearsold,respectively.Onphylogeneticanalysisofthesecond hypervariableregionofthe112RSV-Astrains,110(98.2%)clusteredwithinoradjacenttotheNA1genotype;twoisolates were GA5 genotype. Eleven (10%) NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G) glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplicationresultsinarepeatof7potentialO-glycosylationsitesincludingthreeO-linkedsugaracceptorsatresidues270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observedamongOntarioNA1isolates;sixwerefoundtobecodonswhichrevertedtothepreviousstateobservedinthe prototypeRSV-A2strain.ThetendencyofcodonregressionintheG-ectodomainmayinferadecreased