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Basic Characteristics of Mutations
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Mutation Site
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V31I |
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Mutation Site Sentence
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The latter three substitutions are synonymous: D3E, R20K, and V31I (Fig. 1). IN_CRF differs from IN_A and IN_B by four unique amino acid substitutions in the N-terminal domain: E11D, K14R, S24N, and M50I (Fig. 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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IN |
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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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-
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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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INSTIs |
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Location
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Russia |
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Literature Information
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PMID
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31024744
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Title
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Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1
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Author
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Agapkina YY,Pustovarova MA,Korolev SP,Zyryanova DP,Ivlev VV,Totmenin AV,Gashnikova NM,Gottikh MB
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Journal
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Acta naturae
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Journal Info
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2019 Jan-Mar;11(1):14-22
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Abstract
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The high genetic variability of the human immunodeficiency virus (HIV-1) leads to a constant emergence of new genetic variants, including the recombinant virus CRF63_02A1, which is widespread in the Siberian Federal District of Russia. We studied HIV-1 CRF63_02A1 integrase (IN_CRF) catalyzing the incorporation of viral DNA into the genome of an infected cell. The consensus sequence was designed, recombinant integrase was obtained, and its DNA-binding and catalytic activities were characterized. The stability of the IN_CRF complex with the DNA substrate did not differ from the complex stability for subtype A and B integrases; however, the rate of complex formation was significantly higher. The rates and efficiencies of 3'-processing and strand transfer reactions catalyzed by IN_CRF were found to be higher, too. Apparently, all these distinctive features of IN_CRF may result from specific amino acid substitutions in its N-terminal domain, which plays an important role in enzyme multimerization and binding to the DNA substrate. It was also found that the drug resistance mutations Q148K/G140S and G118R/E138K significantly reduce the catalytic activity of IN_CRF and its sensitivity to the strand transfer inhibitor raltegravir. Reduction in sensitivity to raltegravir was found to be much stronger in the case of double-mutation Q148K/G140S.
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Sequence Data
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-
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