Evolutionary Analysis of Inter-Farm Transmission Dynamics in a Highly Pathogenic Avian Influenza Epidemic 英文参考文献.docVIP

EvolutionaryAnalysisofInter-FarmTransmission DynamicsinaHighlyPathogenicAvianInfluenza Epidemic ArnaudBataille1,2,FrankvanderMeer2,ArjanStegeman1,GuusKoch2* 1DepartmentofFarmAnimalHealth,FacultyofVeterinaryMedicine,UtrechtUniversity,Utrecht,TheNetherlands,2DepartmentofVirology,CentralVeterinaryInstitute, AnimalSciencesGroup,WageningenUniversityandResearchCentre,Lelystad,TheNetherlands Abstract Phylogenetic studies have largely contributed to better understand the emergence, spread and evolution of highly pathogenic avian influenza during epidemics, but sampling of genetic data has never been detailed enough to allow mappingofthespatiotemporalspreadofavianinfluenzavirusesduringasingleepidemic.Here,wepresentgeneticdataof H7N7 viruses produced from 72% of the poultry farms infected during the 2003 epidemic in the Netherlands. We use phylogenetic analyses to unravel the pathways of virus transmission between farms and between infected areas. In addition, we investigated the evolutionary processes shaping viral genetic diversity, and assess how they could have affected our phylogenetic analyses. Our results show that the H7N7 virus was characterized by a high level of genetic diversity driven mainly by a high neutral substitution rate, purifying selection and limited positive selection. We also identifiedpotentialreassortmentinthethreegenesthatwehavetested,buttheyhadonlyalimitedeffectontheresolution oftheinter-farmtransmissionnetwork.Clonalsequencinganalysesperformedonsixfarmsamplesshowedthatatleastone farm sample presented very complex virus diversity and was probably at the origin of chronological anomalies in the transmissionnetwork.However,mostvirussequencescouldbegroupedwithinclearlydefinedandchronologicallysound clusters of infection and some likely transmission events between farms located 0.8–13Km apart were identified. In addition, three farms were found as most likely source of virus introduction in distantly located new areas. These long distance transmissio