HIV-1 Group M Capsid Amino Acid Variability : Implications for Sequence Quality Control of Genotypic Resistance Testing
BACKGROUND: With the approval of the HIV-1 capsid inhibitor, lenacapavir, capsid sequencing will be required for managing lenacapavir-experienced individuals with detectable viremia. Successful sequence interpretation will require examining new capsid sequences in the context of previously published sequence data.
METHODS: We analyzed published HIV-1 group M capsid sequences from 21,012 capsid-inhibitor naïve individuals to characterize amino acid variability at each position and influence of subtype and cytotoxic T lymphocyte (CTL) selection pressure. We determined the distributions of usual mutations, defined as amino acid differences from the group M consensus, with a prevalence ≥ 0.1%. Co-evolving mutations were identified using a phylogenetically-informed Bayesian graphical model method.
RESULTS: 162 (70.1%) positions had no usual mutations (45.9%) or only conservative usual mutations with a positive BLOSUM62 score (24.2%). Variability correlated independently with subtype-specific amino acid occurrence (Spearman rho = 0.83; p < 1 × 10-9) and the number of times positions were reported to contain an HLA-associated polymorphism, an indicator of CTL pressure (rho = 0.43; p = 0.0002).
CONCLUSIONS: Knowing the distribution of usual capsid mutations is essential for sequence quality control. Comparing capsid sequences from lenacapavir-treated and lenacapavir-naïve individuals will enable the identification of additional mutations potentially associated with lenacapavir therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Viruses - 15(2023), 4 vom: 18. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tao, Kaiming [VerfasserIn] |
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| Links: |
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| Themen: |
Amino Acids |
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| Anmerkungen: |
Date Completed 01.05.2023 Date Revised 06.12.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/v15040992 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356165469 |
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| 245 | 1 | 0 | |a HIV-1 Group M Capsid Amino Acid Variability |b Implications for Sequence Quality Control of Genotypic Resistance Testing |
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| 500 | |a Date Revised 06.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: With the approval of the HIV-1 capsid inhibitor, lenacapavir, capsid sequencing will be required for managing lenacapavir-experienced individuals with detectable viremia. Successful sequence interpretation will require examining new capsid sequences in the context of previously published sequence data | ||
| 520 | |a METHODS: We analyzed published HIV-1 group M capsid sequences from 21,012 capsid-inhibitor naïve individuals to characterize amino acid variability at each position and influence of subtype and cytotoxic T lymphocyte (CTL) selection pressure. We determined the distributions of usual mutations, defined as amino acid differences from the group M consensus, with a prevalence ≥ 0.1%. Co-evolving mutations were identified using a phylogenetically-informed Bayesian graphical model method | ||
| 520 | |a RESULTS: 162 (70.1%) positions had no usual mutations (45.9%) or only conservative usual mutations with a positive BLOSUM62 score (24.2%). Variability correlated independently with subtype-specific amino acid occurrence (Spearman rho = 0.83; p < 1 × 10-9) and the number of times positions were reported to contain an HLA-associated polymorphism, an indicator of CTL pressure (rho = 0.43; p = 0.0002) | ||
| 520 | |a CONCLUSIONS: Knowing the distribution of usual capsid mutations is essential for sequence quality control. Comparing capsid sequences from lenacapavir-treated and lenacapavir-naïve individuals will enable the identification of additional mutations potentially associated with lenacapavir therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a HIV-1 | |
| 650 | 4 | |a capsid | |
| 650 | 4 | |a cytotoxic T lymphocytes | |
| 650 | 4 | |a drug resistance | |
| 650 | 4 | |a lenacapavir | |
| 650 | 4 | |a subtype | |
| 650 | 7 | |a Amino Acids |2 NLM | |
| 650 | 7 | |a Capsid Proteins |2 NLM | |
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| 700 | 1 | |a Tzou, Philip L |e verfasserin |4 aut | |
| 700 | 1 | |a Osman, Zachary A |e verfasserin |4 aut | |
| 700 | 1 | |a Pond, Sergei L Kosakovsky |e verfasserin |4 aut | |
| 700 | 1 | |a Holmes, Susan P |e verfasserin |4 aut | |
| 700 | 1 | |a Shafer, Robert W |e verfasserin |4 aut | |
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