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Basic Characteristics of Mutations
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Mutation Site
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G89V |
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Mutation Site Sentence
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To further corroborate these findings, we challenged human PBMCs and CD4+ T cells with increasing amounts of HIV-1-GFP particles bearing the capsid mutations P90A and G89V, both of which prevent CypA-capsid interactions. |
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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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CA |
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Standardized Encoding Gene
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Gag
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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
|
Cyclosporin A |
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Location
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- |
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Literature Information
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PMID
|
32187548
|
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Title
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Cyclophilin A Prevents HIV-1 Restriction in Lymphocytes by Blocking Human TRIM5alpha Binding to the Viral Core
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Author
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Selyutina A,Persaud M,Simons LM,Bulnes-Ramos A,Buffone C,Martinez-Lopez A,Scoca V,Di Nunzio F,Hiatt J,Marson A,Krogan NJ,Hultquist JF,Diaz-Griffero F
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Journal
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Cell reports
|
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Journal Info
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2020 Mar 17;30(11):3766-3777
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Abstract
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Disruption of cyclophilin A (CypA)-capsid interactions affects HIV-1 replication in human lymphocytes. To understand this mechanism, we utilize human Jurkat cells, peripheral blood mononuclear cells (PBMCs), and CD4(+) T cells. Our results show that inhibition of HIV-1 infection caused by disrupting CypA-capsid interactions is dependent on human tripartite motif 5alpha (TRIM5alpha(hu)), showing that TRIM5alpha(hu) restricts HIV-1 in CD4(+) T cells. Accordingly, depletion of TRIM5alpha(hu) in CD4(+) T cells rescues HIV-1 that fail to interact with CypA, such as HIV-1-P90A. We found that TRIM5alpha(hu) binds to the HIV-1 core. Disruption of CypA-capsid interactions fail to affect HIV-1-A92E/G94D infection, correlating with the loss of TRIM5alpha(hu) binding to HIV-1-A92E/G94D cores. Disruption of CypA-capsid interactions in primary cells has a greater inhibitory effect on HIV-1 when compared to Jurkat cells. Consistent with TRIM5alpha restriction, disruption of CypA-capsid interactions in CD4(+) T cells inhibits reverse transcription. Overall, our results reveal that CypA binding to the core protects HIV-1 from TRIM5alpha(hu) restriction.
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Sequence Data
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-
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