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Basic Characteristics of Mutations
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Mutation Site
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I84V |
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Mutation Site Sentence
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Among MDR-1 isolates, the drug resistance-associated amino acid changes in protease, i.e., L10I, L33F, M46I, I54M, L63F, I66F, A71V, G73S, I84V and L90M were shared with all biological clones. |
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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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Y |
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Treatment
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PIs |
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Location
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USA |
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Literature Information
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PMID
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18645523
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Title
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In vitro characterization of multidrug-resistant HIV-1 isolates from a recently infected patient associated with dual tropism and rapid disease progression
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Author
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Mohri H,Markowitz M
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Journal
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Journal of acquired immune deficiency syndromes (1999)
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Journal Info
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2008 Aug 15;48(5):511-21
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Abstract
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OBJECTIVE: Multidrug-resistant (MDR) HIV-1 variants are thought to be less fit than wild-type virus. In 2005, we reported a case of transmitted MDR HIV-1 infection associated with dual tropism and rapid clinical progression. Here we report the in vitro characterization of the virus isolates. METHODS: Replication characteristics of bulk and clonal isolates from this case (MDR-1) were examined and compared with these of a panel of transmitted MDR and wild-type (WT) viruses (MDR-2 approximately 4, WT-1, 2). RESULTS: Infectivity and frequency of infectious virion of propagated isolates were high in MDR-1 biological clones (mean titer, 3.5 x 10(5) TCID50/mL; mean frequency of infectious virion, 1/2444) and its bulk isolate (3.2 x 10(6) TCID50/mL; 1/301) as compared with the other biological clones (7.3 x 10(3) TCID50/mL; 1/21,320). Upslope (log10 p24/mL/d) of viral replication in peripheral blood mononuclear cell culture was much higher in MDR-1 clones (1.30 +/- 0.30: mean +/- SD) than those of MDR-2 approximately 4 (0.75 +/- 0.08) or WT-1, WT-2 clones (0.82 +/- 0.03). The bulk isolate and dual-tropic biological clones from MDR-1 depleted CD4+ T cells very rapidly in vitro compared with the other viruses tested. CONCLUSIONS: These findings support the hypothesis that MDR HIV-1 can effectively evolve and compensate not only to retain high-level replication but also to exhibit virulence associated with rapid disease progression.
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Sequence Data
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-
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