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Basic Characteristics of Mutations
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Mutation Site
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E478Q |
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Mutation Site Sentence
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However, it was shown that the mutation of one of the residues required for binding of the divalent metal ions in the RNaseH active site of RT, E478Q, eliminated the cleavage of both RNA in an RNA/RNA hybrid and RNA in a DNA/RNA hybrid, suggesting that this activity is inherent to RNaseH. |
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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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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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pHXB2-RT
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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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- |
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Literature Information
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PMID
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33374603
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Title
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Extended Interactions between HIV-1 Viral RNA and tRNA(Lys3) Are Important to Maintain Viral RNA Integrity
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Author
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Gremminger T,Song Z,Ji J,Foster A,Weng K,Heng X
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Journal
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International journal of molecular sciences
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Journal Info
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2020 Dec 23;22(1):58
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Abstract
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The reverse transcription of the human immunodeficiency virus 1 (HIV-1) initiates upon annealing of the 3'-18-nt of tRNA(Lys3) onto the primer binding site (PBS) in viral RNA (vRNA). Additional intermolecular interactions between tRNA(Lys3) and vRNA have been reported, but their functions remain unclear. Here, we show that abolishing one potential interaction, the A-rich loop: tRNA(Lys3) anticodon interaction in the HIV-1 MAL strain, led to a decrease in viral infectivity and reduced the synthesis of reverse transcription products in newly infected cells. In vitro biophysical and functional experiments revealed that disruption of the extended interaction resulted in an increased affinity for reverse transcriptase (RT) and enhanced primer extension efficiency. In the absence of deoxyribose nucleoside triphosphates (dNTPs), vRNA was degraded by the RNaseH activity of RT, and the degradation rate was slower in the complex with the extended interaction. Consistently, the loss of vRNA integrity was detected in virions containing A-rich loop mutations. Similar results were observed in the HIV-1 NL4.3 strain, and we show that the nucleocapsid (NC) protein is necessary to promote the extended vRNA: tRNA(Lys3) interactions in vitro. In summary, our data revealed that the additional intermolecular interaction between tRNA(Lys3) and vRNA is likely a conserved mechanism among various HIV-1 strains and protects the vRNA from RNaseH degradation in mature virions.
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Sequence Data
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-
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