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Basic Characteristics of Mutations
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Mutation Site
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D15E |
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Mutation Site Sentence
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In addition to Gag–Pol, Pol was readily detected in G2AP/P22A transfectant supernatant samples, but barely detected in G2AP/D15E (Figure 3B upper panel lane 7 vs. lane 9), suggesting that the D15E mutation is more effective than the P22A mutation in terms of 2A cleavage activity inhibition. |
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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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RT |
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Standardized Encoding Gene
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gag-pol:155348
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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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- |
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Literature Information
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PMID
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31906562
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Title
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HIV-1 Mutant Assembly, Processing and Infectivity Expresses Pol Independent of Gag
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Author
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Yu FH,Huang KJ,Wang CT
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Journal
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Viruses
|
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Journal Info
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2020 Jan 2;12(1):54
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Abstract
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The pol retrovirus gene encodes required enzymes for virus replication and maturation. Unlike HIV-1 Pol (expressed as a Gag-Pol fusion protein), foamy virus (described as an ancient retrovirus) expresses Pol without forming Gag-Pol polyproteins. We placed a ""self-cleaving"" 2A peptide between HIV-1 Gag and Pol. This construct, designated G2AP, is capable of producing virions with the same density as a wild-type (wt) HIV-1 particle. The 2A peptide allows for Pol to be packaged into virions independently from Gag following co-translationally cleaved from Gag. We found that G2AP exhibited only one-third the virus infectivity of the wt, likely due, at least in part, to defects in Pol packaging. Attenuated protease (PR) activity, or a reduction in Pol expression due to the placement of 2A-mediated Pol in a normal Gag-Pol frameshift context, resulted in significant increases in virus yields and/or titers. This suggests that reduced G2AP virus yields were largely due to increased PR activity associated with overexpressed Pol. Our data suggest that HIV-1 adopts a gag/pol ribosomal frameshifting mechanism to support virus assembly via the efficient modulation of Gag-Pol/Gag expression, as well as to promote viral enzyme packaging. Our results help clarify the molecular basis of HIV-1 gene expression and assembly.
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Sequence Data
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-
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