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Basic Characteristics of Mutations
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Mutation Site
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C54F |
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Mutation Site Sentence
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This revealed several interesting features: (i) some mutations were observed both during in vivo and in vitro experiments (Fig 3, red characters: mutations H to Q in position 38 of the P protein (P-H38Q), P-L39R, M-G57R or E, L-L65Q, L-T612I, L-Y613X, L-K1234R); (ii) approximately 50% of these mutations have a frequency among global RABV populations of less than 10% (light yellow rectangles); (iii) in some passages mutations appear in both the brain and the salivary glands and are further transmitted in the following passages, the most significant of which were: M-F150L in 'vDog on dog'; N-N61I and G-C480F in 'vDog on fox'; M-C54F, L-P4S and L-P275L in 'vFox on fox'; (iv) all mutations whose frequency was above 50% were observed both in the brain and in the salivary glands, although this was not always the case for other minor variants; and (v) very few mutations are present in all the replicates (in vivo: N-A97E; in vitro: P-H38Q, P-L39R). |
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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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M |
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Standardized Encoding Gene
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M
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Genotype/Subtype
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Ariana2;91047FRA |
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Viral Reference
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KX148127;KF155001.1
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Functional Impact and Mechanisms
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Disease
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Rabies Virus infection
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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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Tunisia;France |
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Literature Information
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PMID
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31220188
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Title
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Comparison of intra- and inter-host genetic diversity in rabies virus during experimental cross-species transmission
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Author
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Bonnaud EM,Troupin C,Dacheux L,Holmes EC,Monchatre-Leroy E,Tanguy M,Bouchier C,Cliquet F,Barrat J,Bourhy H
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Journal
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PLoS pathogens
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Journal Info
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2019 Jun 20;15(6):e1007799
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Abstract
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The development of high-throughput genome sequencing enables accurate measurements of levels of sub-consensus intra-host virus genetic diversity and analysis of the role played by natural selection during cross-species transmission. We analysed the natural and experimental evolution of rabies virus (RABV), an important example of a virus that is able to make multiple host jumps. In particular, we (i) analyzed RABV evolution during experimental host switching with the goal of identifying possible genetic markers of host adaptation, (ii) compared the mutational changes observed during passage with those observed in natura, and (iii) determined whether the colonization of new hosts or tissues requires adaptive evolution in the virus. To address these aims, animal infection models (dog and fox) and primary cell culture models (embryo brain cells of dog and fox) were developed and viral variation was studied in detail through deep genome sequencing. Our analysis revealed a strong unidirectional host evolutionary effect, as dog-adapted rabies virus was able to replicate in fox and fox cells relatively easily, while dogs or neuronal dog cells were not easily susceptible to fox adapted-RABV. This suggests that dog RABV may be able to adapt to some hosts more easily than other host variants, or that when RABV switched from dogs to red foxes it lost its ability to adapt easily to other species. Although no difference in patterns of mutation variation between different host organs was observed, mutations were common following both in vitro and in vivo passage. However, only a small number of these mutations also appeared in natura, suggesting that adaptation during successful cross-species virus transmission is a complex, multifactorial evolutionary process.
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Sequence Data
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MK981888;KX148127
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