دورية أكاديمية
HIV-1 Group M Capsid Amino Acid Variability: Implications for Sequence Quality Control of Genotypic Resistance Testing
| العنوان: | HIV-1 Group M Capsid Amino Acid Variability: Implications for Sequence Quality Control of Genotypic Resistance Testing |
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| المؤلفون: | Kaiming Tao, Soo-Yon Rhee, Philip L. Tzou, Zachary A. Osman, Sergei L. Kosakovsky Pond, Susan P. Holmes, Robert W. Shafer |
| المصدر: | Viruses, Vol 15, Iss 4, p 992 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Microbiology |
| مصطلحات موضوعية: | HIV-1, capsid, lenacapavir, drug resistance, subtype, cytotoxic T lymphocytes, Microbiology, QR1-502 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 15040992 1999-4915 |
| Relation: | https://www.mdpi.com/1999-4915/15/4/992; https://doaj.org/toc/1999-4915 |
| DOI: | 10.3390/v15040992 |
| URL الوصول: | https://doaj.org/article/660e68dcdb55445589d9c342138cbab0 |
| رقم الأكسشن: | edsdoj.660e68dcdb55445589d9c342138cbab0 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15040992 19994915 |
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| DOI: | 10.3390/v15040992 |