HIV-1 Protease, Reverse Transcriptase, and Integrase Variation
HIV-1 protease (PR), reverse transcriptase (RT), and integrase (IN) variability presents a challenge to laboratories performing genotypic resistance testing. This challenge will grow with increased sequencing of samples enriched for proviral DNA such as dried blood spots and increased use of next-ge...
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| Format: | Online |
| Language: | English |
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American Society for Microbiology
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907232/ |
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pubmed-4907232 |
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pubmed-49072322016-07-01 HIV-1 Protease, Reverse Transcriptase, and Integrase Variation Rhee, Soo-Yon Sankaran, Kris Varghese, Vici Winters, Mark A. Hurt, Christopher B. Eron, Joseph J. Parkin, Neil Holmes, Susan P. Holodniy, Mark Shafer, Robert W. Genetic Diversity and Evolution HIV-1 protease (PR), reverse transcriptase (RT), and integrase (IN) variability presents a challenge to laboratories performing genotypic resistance testing. This challenge will grow with increased sequencing of samples enriched for proviral DNA such as dried blood spots and increased use of next-generation sequencing (NGS) to detect low-abundance HIV-1 variants. We analyzed PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to characterize variation at each amino acid position, identify mutations indicating APOBEC-mediated G-to-A editing, and identify mutations resulting from selective drug pressure. Forty-seven percent of PR, 37% of RT, and 34% of IN positions had one or more amino acid variants with a prevalence of ≥1%. Seventy percent of PR, 60% of RT, and 60% of IN positions had one or more variants with a prevalence of ≥0.1%. Overall 201 PR, 636 RT, and 346 IN variants had a prevalence of ≥0.1%. The median intersubtype prevalence ratios were 2.9-, 2.1-, and 1.9-fold for these PR, RT, and IN variants, respectively. Only 5.0% of PR, 3.7% of RT, and 2.0% of IN variants had a median intersubtype prevalence ratio of ≥10-fold. Variants at lower prevalences were more likely to differ biochemically and to be part of an electrophoretic mixture compared to high-prevalence variants. There were 209 mutations indicative of APOBEC-mediated G-to-A editing and 326 mutations nonpolymorphic treatment selected. Identification of viruses with a high number of APOBEC-associated mutations will facilitate the quality control of dried blood spot sequencing. Identifying sequences with a high proportion of rare mutations will facilitate the quality control of NGS. American Society for Microbiology 2016-06-10 /pmc/articles/PMC4907232/ /pubmed/27099321 http://dx.doi.org/10.1128/JVI.00495-16 Text en Copyright © 2016 Rhee et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Rhee, Soo-Yon Sankaran, Kris Varghese, Vici Winters, Mark A. Hurt, Christopher B. Eron, Joseph J. Parkin, Neil Holmes, Susan P. Holodniy, Mark Shafer, Robert W. |
| spellingShingle |
Rhee, Soo-Yon Sankaran, Kris Varghese, Vici Winters, Mark A. Hurt, Christopher B. Eron, Joseph J. Parkin, Neil Holmes, Susan P. Holodniy, Mark Shafer, Robert W. HIV-1 Protease, Reverse Transcriptase, and Integrase Variation |
| author_facet |
Rhee, Soo-Yon Sankaran, Kris Varghese, Vici Winters, Mark A. Hurt, Christopher B. Eron, Joseph J. Parkin, Neil Holmes, Susan P. Holodniy, Mark Shafer, Robert W. |
| author_sort |
Rhee, Soo-Yon |
| title |
HIV-1 Protease, Reverse Transcriptase, and Integrase Variation |
| title_short |
HIV-1 Protease, Reverse Transcriptase, and Integrase Variation |
| title_full |
HIV-1 Protease, Reverse Transcriptase, and Integrase Variation |
| title_fullStr |
HIV-1 Protease, Reverse Transcriptase, and Integrase Variation |
| title_full_unstemmed |
HIV-1 Protease, Reverse Transcriptase, and Integrase Variation |
| title_sort |
hiv-1 protease, reverse transcriptase, and integrase variation |
| description |
HIV-1 protease (PR), reverse transcriptase (RT), and integrase (IN) variability presents a challenge to laboratories performing genotypic resistance testing. This challenge will grow with increased sequencing of samples enriched for proviral DNA such as dried blood spots and increased use of next-generation sequencing (NGS) to detect low-abundance HIV-1 variants. We analyzed PR and RT sequences from >100,000 individuals and IN sequences from >10,000 individuals to characterize variation at each amino acid position, identify mutations indicating APOBEC-mediated G-to-A editing, and identify mutations resulting from selective drug pressure. Forty-seven percent of PR, 37% of RT, and 34% of IN positions had one or more amino acid variants with a prevalence of ≥1%. Seventy percent of PR, 60% of RT, and 60% of IN positions had one or more variants with a prevalence of ≥0.1%. Overall 201 PR, 636 RT, and 346 IN variants had a prevalence of ≥0.1%. The median intersubtype prevalence ratios were 2.9-, 2.1-, and 1.9-fold for these PR, RT, and IN variants, respectively. Only 5.0% of PR, 3.7% of RT, and 2.0% of IN variants had a median intersubtype prevalence ratio of ≥10-fold. Variants at lower prevalences were more likely to differ biochemically and to be part of an electrophoretic mixture compared to high-prevalence variants. There were 209 mutations indicative of APOBEC-mediated G-to-A editing and 326 mutations nonpolymorphic treatment selected. Identification of viruses with a high number of APOBEC-associated mutations will facilitate the quality control of dried blood spot sequencing. Identifying sequences with a high proportion of rare mutations will facilitate the quality control of NGS. |
| publisher |
American Society for Microbiology |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907232/ |
| _version_ |
1613594464706625536 |