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Basic Characteristics of Mutations
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Mutation Site
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N51T |
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Mutation Site Sentence
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Previous reports indicated that some naturally occurring mutations in Nef could affect both SERINC3 and SERINC5 (N51T, H116N, V148L/X, 161N and M168I/X), while others only affected SERINC3 (8R, 9S, 11P, 12G, 14A, 15A, 21K, 28E, 43I, 182E and 188S) or SERINC5 (14S, 21R, 54D, 63E, 81F, 120F, 157N and 158K). |
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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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Nef |
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Standardized Encoding Gene
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Nef
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Genotype/Subtype
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HIV-1 B |
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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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Amsterdam |
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Literature Information
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PMID
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33800773
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Title
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Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction
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Author
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Kruize Z,van Nuenen AC,van Wijk SW,Girigorie AF,van Dort KA,Booiman T,Kootstra NA
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Journal
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Viruses
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Journal Info
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2021 Mar 6;13(3):423
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Abstract
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Nef is a multifunctional viral protein that has the ability to downregulate cell surface molecules, including CD4 and major histocompatibility complex class I (MHC-I) and, as recently shown, also members of the serine incorporator family (SERINC). Here, we analyzed the impact of naturally occurring mutations in HIV-1 Nef on its ability to counteract SERINC restriction and the clinical course of infection. HIV-1 Nef sequences were obtained from 123 participants of the Amsterdam Cohort Studies and showed multiple amino acid variations and mutations. Most of the primary Nef proteins showed increased activity to counteract SERINC3 and SERINC5 as compared to NL4-3 Nef. Several mutations in Nef were associated with either an increased or decreased infectivity of Bal26-pseudotyped HIV-1 produced in the presence of SERINC3 or SERINC5. The 8R, 157N and R178G Nef mutations were shown to have an effect on disease progression. Survival analysis showed an accelerated disease progression of individuals infected with HIV-1 carrying arginine or asparagine at position 8 or 157 in Nef, respectively, or the R178G Nef mutation. Here, we observed that naturally occurring mutations in Nef affect the ability of Nef to counteract SERINC3- and SERINC5-mediated inhibition of viral infectivity. The majority of these Nef mutations had no significant effect on HIV-1 pathogenesis and only the 8R, 157N and R178G mutations were associated with disease course.
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Sequence Data
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-
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