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Basic Characteristics of Mutations
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Mutation Site
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G359S |
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Mutation Site Sentence
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Of those, 12 had increased prevalence in treated sequences (R358K, G359S, A360T, A360V, K366R, A371V, K390R, A400T, I506L, K527N, K530R and Q547K). |
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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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Pol |
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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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- |
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Location
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Brazilian |
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Literature Information
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PMID
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18335052
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Title
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Conservation patterns of HIV-1 RT connection and RNase H domains: identification of new mutations in NRTI-treated patients
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Author
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Santos AF,Lengruber RB,Soares EA,Jere A,Sprinz E,Martinez AM,Silveira J,Sion FS,Pathak VK,Soares MA
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Journal
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PloS one
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Journal Info
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2008 Mar 12;3(3):e1781
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Abstract
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BACKGROUND: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood. METHODS AND FINDINGS: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naive and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher's exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. CONCLUSIONS: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions.
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Sequence Data
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-
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