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Basic Characteristics of Mutations
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Mutation Site
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E35D |
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Mutation Site Sentence
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NL4-3-Δenv-eGFP MDR1 and MDR2 encode the following drug resistance associated mutations (MDR1 Protease: L10V, I13V, G16A, K20R, E35D, M36I, R41K, I64V, H69K, A71V, I84V, L90M, I93M; MDR1 RT: E6K, V35K, M41L, K49R, I50V, L74V, L100I, K103N, K122E, D123E, I135L; MDR2 Protease: I13V, I64V, V77I, L90M; MDR2 RT: M41L, K43E, S68G, V106A, K122E, D123E, I135T, see also Table 1). |
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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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PR |
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Standardized Encoding Gene
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gag-pol
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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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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Protease |
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Location
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- |
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Literature Information
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PMID
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32053707
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Title
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HIV protease cleaves the antiviral m6A reader protein YTHDF3 in the viral particle
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Author
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Jurczyszak D,Zhang W,Terry SN,Kehrer T,Bermudez Gonzalez MC,McGregor E,Mulder LCF,Eckwahl MJ,Pan T,Simon V
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Journal
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PLoS pathogens
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Journal Info
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2020 Feb 13;16(2):e1008305
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Abstract
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N6-methyladenosine (m6A) is the most abundant HIV RNA modification but the interplay between the m6A reader protein YTHDF3 and HIV replication is not well understood. We found that knockout of YTHDF3 in human CD4+ T-cells increases infection supporting the role of YTHDF3 as a restriction factor. Overexpression of the YTHDF3 protein in the producer cells reduces the infectivity of the newly produced viruses. YTHDF3 proteins are incorporated into HIV particles in a nucleocapsid-dependent manner permitting the m6A reader protein to limit infection in the new target cell at the step of reverse transcription. Importantly, HIV protease cleaves the virion-incorporated full-length YTHDF3 protein, a process which is blocked by HIV protease inhibitors used to treat HIV infected patients. Mass-spectrometry confirmed the proteolytic processing of YTHDF3 in the virion. Thus, HIV protease cleaves the virion-encapsidated host m6A effector protein in addition to the viral polyproteins to ensure optimal infectivity of the mature virion.
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Sequence Data
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-
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