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Basic Characteristics of Mutations
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Mutation Site
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P203L |
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Mutation Site Sentence
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We also tested two additional HIV-1 Env CT mutants: one of these was an Env P714L mutant (also called P203L) that was selected for resistance to cholesterol depletion; and the other was the Env 716Ins-R* mutant, which is cleaved by the HIV-1 protease (PR) in a similar fashion to P714L. |
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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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Env |
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Standardized Encoding Gene
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Env
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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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cholesterol depletion |
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Location
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- |
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Literature Information
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PMID
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33515546
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Title
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Ceramide synthase 2 deletion decreases the infectivity of HIV-1
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Author
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Barklis E,Alfadhli A,Kyle JE,Bramer LM,Bloodsworth KJ,Barklis RL,Leier HC,Petty RM,Zelnik ID,Metz TO,Futerman AH,Tafesse FG
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Journal
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The Journal of biological chemistry
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Journal Info
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2021 Jan-Jun;296:100340
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Abstract
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The lipid composition of HIV-1 virions is enriched in sphingomyelin (SM), but the roles that SM or other sphingolipids (SLs) might play in the HIV-1 replication pathway have not been elucidated. In human cells, SL levels are regulated by ceramide synthase (CerS) enzymes that produce ceramides, which can be converted to SMs, hexosylceramides, and other SLs. In many cell types, CerS2, which catalyzes the synthesis of very long chain ceramides, is the major CerS. We have examined how CerS2 deficiency affects the assembly and infectivity of HIV-1. As expected, we observed that very long chain ceramide, hexosylceramide, and SM were reduced in CerS2 knockout cells. CerS2 deficiency did not affect HIV-1 assembly or the incorporation of the HIV-1 envelope (Env) protein into virus particles, but it reduced the infectivites of viruses produced in the CerS2-deficient cells. The reduced viral infection levels were dependent on HIV-1 Env, since HIV-1 particles that were pseudotyped with the vesicular stomatitis virus glycoprotein did not exhibit reductions in infectivity. Moreover, cell-cell fusion assays demonstrated that the functional defect of HIV-1 Env in CerS2-deficient cells was independent of other viral proteins. Overall, our results indicate that the altered lipid composition of CerS2-deficient cells specifically inhibit the HIV-1 Env receptor binding and/or fusion processes.
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Sequence Data
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-
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