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Basic Characteristics of Mutations
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Mutation Site
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Q58E |
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Mutation Site Sentence
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Virus 08-175 was found to have four major PI resistance mutations in PR: M46I, I54L, I84V, L90M and four accessory mutations: L10F, L33F, Q58E, and G73T and was predicted to have high-level resistance to all PIs except darunavir, to which it has intermediate resistance. |
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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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PR |
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Standardized Encoding Gene
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gag-pol
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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NL4-3
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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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PIs |
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Location
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- |
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Literature Information
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PMID
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33093566
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Title
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Nanoscale flow cytometry reveals interpatient variability in HIV protease activity that correlates with viral infectivity and identifies drug-resistant viruses
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Author
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Bonar MM,Tabler CO,Haqqani AA,Lapointe LE,Galiatsos JA,Joussef-Pina S,Quinones-Mateu ME,Tilton JC
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Journal
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Scientific reports
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Journal Info
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2020 Oct 22;10(1):18101
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Abstract
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HIV encodes an aspartyl protease that is activated during, or shortly after, budding of viral particles from the surface of infected cells. Protease-mediated cleavage of viral polyproteins is essential to generating infectious viruses, a process known as 'maturation' that is the target of FDA-approved antiretroviral drugs. Most assays to monitor protease activity rely on bulk analysis of millions of viruses and obscure potential heterogeneity of protease activation within individual particles. In this study we used nanoscale flow cytometry in conjunction with an engineered FRET reporter called VIral ProteasE Reporter (VIPER) to investigate heterogeneity of protease activation in individual, patient-derived viruses. We demonstrate previously unappreciated interpatient variation in HIV protease processing efficiency that impacts viral infectivity. Additionally, monitoring of protease activity in individual virions distinguishes between drug sensitivity or resistance to protease inhibitors in patient-derived samples. These findings demonstrate the feasibility of monitoring enzymatic processes using nanoscale flow cytometry and highlight the potential of this technology for translational clinical discovery, not only for viruses but also other submicron particles including exosomes, microvesicles, and bacteria.
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Sequence Data
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-
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