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Basic Characteristics of Mutations
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Mutation Site
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I417V |
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Mutation Site Sentence
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Among these mutations however, four were found in envelope glycoprotein complexes I, II and III, and were therefore considered the most plausible candidates for a causal relation with the partial resistance against the entry inhibitor GT40, i.e., L47P in gO, I417V in gH, D84Y in gN and H177N in gB (Figure 4A). |
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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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gH |
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Standardized Encoding Gene
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UL75
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Genotype/Subtype
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- |
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Viral Reference
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KU317610.1
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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PDGFRA
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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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34201364
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Title
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Selection of Human Cytomegalovirus Mutants with Resistance against PDGFRalpha-Derived Entry Inhibitors
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Author
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Laib Sampaio K,Lutz C,Engels R,Stohr D,Sinzger C
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Journal
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Viruses
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Journal Info
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2021 Jun 8;13(6):1094
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Abstract
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The human cytomegalovirus (HCMV) infects fibroblasts via an interaction of its envelope glycoprotein gO with the cellular platelet-derived growth factor receptor alpha (PDGFRalpha), and soluble derivatives of this receptor can inhibit viral entry. We aimed to select mutants with resistance against PDGFRalpha-Fc and the PDGFRalpha-derived peptides GT40 and IK40 to gain insight into the underlying mechanisms and determine the genetic barrier to resistance. An error-prone variant of strain AD169 was propagated in the presence of inhibitors, cell cultures were monitored weekly for signs of increased viral growth, and selected viruses were tested regarding their sensitivity to the inhibitor. Resistant virus was analyzed by DNA sequencing, candidate mutations were transferred into AD169 clone pHB5 by seamless mutagenesis, and reconstituted virus was again tested for loss of sensitivity by dose-response analyses. An S48Y mutation in gO was identified that conferred a three-fold loss of sensitivity against PDGFRalpha-Fc, a combination of mutations in gO, gH, gB and gN reduced sensitivity to GT40 by factor 4, and no loss of sensitivity occurred with IK40. The resistance-conferring mutations support the notion that PDGFRalpha-Fc and GT40 perturb the interaction of gO with its receptor, but the relatively weak effect indicates a high genetic barrier to resistance.
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Sequence Data
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MZ327301
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