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Basic Characteristics of Mutations
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Mutation Site
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D701N |
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Mutation Site Sentence
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Thus, the amino acid change PB2 D701N favors the transmission of an H5N1 virus in a mammalian host and this mutation fully compensates for the lack of a lysine at position 627 in terms of transmission by the contact route. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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PB2 |
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Standardized Encoding Gene
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PB2
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Genotype/Subtype
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H5N1 |
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Viral Reference
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DQ487334;AY651719
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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Panama;Vietnam |
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Literature Information
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PMID
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19119420
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Title
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Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N
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Author
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Steel J,Lowen AC,Mubareka S,Palese P
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Journal
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PLoS pathogens
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Journal Info
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2009 Jan;5(1):e1000252
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Abstract
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Since 2003, more than 380 cases of H5N1 influenza virus infection of humans have been reported. Although the resultant disease in these cases was often severe or fatal, transmission of avian influenza viruses between humans is rare. The precise nature of the barrier blocking human-to-human spread is unknown. It is clear, however, that efficient human-to-human transmission of an antigenically novel influenza virus would result in a pandemic. Influenza viruses with changes at amino acids 627 or 701 of the PB2 protein have been isolated from human cases of highly pathogenic H5 and H7 avian influenza. Herein, we have used the guinea pig model to test the contributions of PB2 627 and 701 to mammalian transmission. To this end, viruses carrying mutations at these positions were generated in the A/Panama/2007/99 (H3N2) and A/Viet Nam/1203/04 (H5N1) backgrounds. In the context of either rPan99 or rVN1203, mutation of lysine 627 to the avian consensus residue glutamic acid was found to decrease transmission. Introduction of an asparagine at position 701, in conjunction with the K627E mutation, resulted in a phenotype more similar to that of the parental strains, suggesting that this residue can compensate for the lack of 627K in terms of increasing transmission in mammals. Thus, our data show that PB2 amino acids 627 and 701 are determinants of mammalian inter-host transmission in diverse virus backgrounds.
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Sequence Data
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-
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