Mutagenesis analysis of T380R mutation in the envelope protein of yellow fever virus

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Show simple item record Huang, Yan-Jang S. Nuckols, John T. Horne, Kate M. Vanlandingham, Dana L. Lobigs, Mario Higgs, Stephen 2014-06-17T21:47:33Z 2014-06-17T21:47:33Z 2014-06-17
dc.description.abstract Background: The RGD motif in the mosquito-borne flaviviruses envelope protein domain III (EDIII) FG loop was shown to bind negatively charged cellular molecules and mediate virus entry in mammals. However, its importance in virus entry in the mosquito has not yet been defined. The sequences of RGD motifs are conserved in JEV-serocomplex members primarily transmitted by Culex mosquitoes but absent from members of the DENV serocomplex, which utilize Aedes mosquitoes as vectors. Interestingly, the RGD sequence is present in the attenuated 17D strain of yellow fever virus as a result of the T380R mutation in the EDIII of Asibi strain following extensive in vitro passage in mice and chicken embryos and was found to contribute to the more rapid clearance in mice challenged with 17D. However, viral infectivity and dissemination in mosquitoes had not been evaluated for this mutant. Findings: The study utilized the reverse genetics system of YFV and Ae. aegypti RexD WE mosquitoes to assess the impact of a T380R mutation in YFV Asibi and 17D/Asibi M-E chimera. The T380R mutation led to higher infection rates but similar dissemination rates when introduced into the YFV Asibi strain and 17D/Asibi M-E chimera. Conclusions: While the increase of the positive charge in EDIII may reduce the virulence of YFV in mice, this mutation favored the establishment of the viral infection in Ae. aegypti. However, such gain in viral infectivity did not increase dissemination in infected mosquitoes. en_US
dc.language.iso en_US en_US
dc.relation.uri en_US
dc.subject Yellow fever virus en_US
dc.subject 17D vaccine en_US
dc.subject Aedes aegypti en_US
dc.title Mutagenesis analysis of T380R mutation in the envelope protein of yellow fever virus en_US
dc.type Article (publisher version) en_US 2014 en_US
dc.citation.doi doi:10.1186/1743-422X-11-60 en_US
dc.citation.jtitle Virology Journal en_US
dc.citation.spage 60 en_US
dc.citation.volume 11 en_US
dc.contributor.authoreid kmhorne en_US
dc.contributor.authoreid dlvanlan en_US
dc.contributor.authoreid shiggs en_US

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