Amino Acid Prevalence of HIV-1 pol Mutations by Direct Polymerase Chain Reaction and Single Genome Sequencing.
AIDS Res Hum Retroviruses
; 35(10): 924-929, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31317771
ABSTRACT
The presence of many highly unusual HIV-1 mutations at a minority variant threshold by next-generation sequence (NGS) may indicate that a high proportion of variants at or just above the threshold represent PCR errors. The validity of this hypothesis depends on the concept that highly unusual mutations detected by population-based sequencing are also highly unusual within a person's virus population. Highly unusual mutations were defined as mutations with a prevalence <0.01% in group M HIV-1 direct PCR population-based Sanger sequences in the Stanford HIV Drug Resistance Database. Single genome Sanger sequences [single genome sequences (SGSs)] were analyzed because they are not subject to PCR error. Permutation analyses compared the proportion of highly unusual mutations in SGSs with the empirical frequencies of these mutations in repeated random selections of population-based sequences. We created a database of 11,258 pol SGSs in 963 plasma samples from 345 persons with active virus replication and analyzed the subset of samples containing 10 or more SGSs. Highly unusual mutations occurred more commonly in samples undergoing SGS compared with population-based sequencing in protease (3.9% vs. 0.8%; p < .001), reverse transcriptase (6.5% vs. 1.5%; p < .001), and integrase (5.0% vs. 1.8%; p < .001). Highly unusual mutations occur more commonly in SGSs than in population-based sequences. However, they comprise a small proportion of all SGS mutations supporting the concept that the presence of many highly unusual mutations just above an NGS threshold suggests that the threshold is too low.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Viremia
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RNA Viral
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Genes pol
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Infecções por HIV
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HIV-1
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Reação em Cadeia da Polimerase Via Transcriptase Reversa
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Mutação de Sentido Incorreto
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Produtos do Gene pol do Vírus da Imunodeficiência Humana
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Sequenciamento de Nucleotídeos em Larga Escala
Tipo de estudo:
Prevalence_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article