Epistatic Roles of E2 Glycoprotein Mutations in Adaption of Chikungunya Virus to Aedes Albopictus and Ae. Aegypti Mosquitoes 英文参考文献.docVIP
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Epistatic Roles of E2 Glycoprotein Mutations in Adaption of Chikungunya Virus to Aedes Albopictus and Ae. Aegypti Mosquitoes 英文参考文献
EpistaticRolesofE2GlycoproteinMutationsinAdaption
ofChikungunyaVirustoAedesAlbopictusandAe.
AegyptiMosquitoes
KonstantinA.Tsetsarkin*,CharlesE.McGee,SaraM.Volk,DanaL.Vanlandingham,ScottC.Weaver,
StephenHiggs
DepartmentofPathology,UniversityofTexasMedicalBranch,Galveston,Texas,UnitedStatesofAmerica
Abstract
Between 2005 and 2007 Chikungunya virus (CHIKV) caused its largest outbreak/epidemic in documented history. An
unusualfeatureofthisepidemicistheinvolvementofAe.albopictusasaprincipalvector.Previouslywehavedemonstrated
thatasinglemutationE1-A226Vsignificantlychangedtheabilityofthevirustoinfectandbetransmittedbythisvector
whenexpressedinthebackgroundofwellcharacterizedCHIKVstrainsLR2006OPY1and37997.However,inthecurrent
studywedemonstratethatintroductionoftheE1-A226Vmutationintothebackgroundofaninfectiousclonederivedfrom
the Ag41855 strain (isolated in Uganda in 1982) does not significantly increase infectivity for Ae. albopictus. In order to
elucidatethegeneticdeterminantsthataffectCHIKVsensitivitytotheE1-A226VmutationinAe.albopictus,thegenomesof
the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific
combinationofpointmutationsatselectedpositions.BaseduponthemidgutinfectionratesofthederivedvirusesinAe.
albopictusandAe.aegyptimosquitoes,acriticalroleofthemutationsatpositionsE2-60andE2-211onvectorinfectionwas
revealed.TheE2-G60DmutationwasanimportantdeterminantofCHIKVinfectivityforbothAe.albopictusandAe.aegypti,
butonlymoderatelymodulatedtheeffectoftheE1-A226VmutationinAe.albopictus.However,theeffectoftheE2-I211T
mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V
mutationinAe.albopictus.Incontrast,CHIKVinfectivityforAe.aegyptiwasnotinfluencedbytheE2-1211Tmutation.The
occurrenceoftheE2-60GandE2-211IresiduesamongCHIKVisolateswasanalyzed,revealingahighprevalenceofE2-211I
among strains belonging to the Eastern/Central/South African (ECSA) clade. This s
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