Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance.
Detection of recent HIV infections is a prerequisite for reliable estimations of transmitted HIV drug resistance (t-HIVDR) and incidence. However, accurately identifying recent HIV infection is challenging due partially to the limitations of current serological tests. Ambiguous nucleotides are newly...
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doaj-dede984077b941eaa58794c2837e94182020-11-24T21:08:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7764910.1371/journal.pone.0077649Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance.Du-Ping ZhengMargarida RodriguesEbi BileDuc B NguyenKaridia DialloJoshua R DeVosJohn N NkengasongChunfu YangDetection of recent HIV infections is a prerequisite for reliable estimations of transmitted HIV drug resistance (t-HIVDR) and incidence. However, accurately identifying recent HIV infection is challenging due partially to the limitations of current serological tests. Ambiguous nucleotides are newly emerged mutations in quasispecies, and accumulate by time of viral infection. We utilized ambiguous mutations to establish a measurement for detecting recent HIV infection and monitoring early HIVDR development. Ambiguous nucleotides were extracted from HIV-1 pol-gene sequences in the datasets of recent (HIVDR threshold surveys [HIVDR-TS] in 7 countries; n=416) and established infections (1 HIVDR monitoring survey at baseline; n=271). An ambiguous mutation index of 2.04×10(-3) nts/site was detected in HIV-1 recent infections which is equivalent to the HIV-1 substitution rate (2×10(-3) nts/site/year) reported before. However, significantly higher index (14.41×10(-3) nts/site) was revealed with established infections. Using this substitution rate, 75.2% subjects in HIVDR-TS with the exception of the Vietnam dataset and 3.3% those in HIVDR-baseline were classified as recent infection within one year. We also calculated mutation scores at amino acid level at HIVDR sites based on ambiguous or fitted mutations. The overall mutation scores caused by ambiguous mutations increased (0.54×10(-2)3.48×10(-2)/DR-site) whereas those caused by fitted mutations remained stable (7.50-7.89×10(-2)/DR-site) in both recent and established infections, indicating that t-HIVDR exists in drug-naïve populations regardless of infection status in which new HIVDR continues to emerge. Our findings suggest that characterization of ambiguous mutations in HIV may serve as an additional tool to differentiate recent from established infections and to monitor HIVDR emergence.http://europepmc.org/articles/PMC3798419?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Du-Ping Zheng Margarida Rodrigues Ebi Bile Duc B Nguyen Karidia Diallo Joshua R DeVos John N Nkengasong Chunfu Yang |
spellingShingle |
Du-Ping Zheng Margarida Rodrigues Ebi Bile Duc B Nguyen Karidia Diallo Joshua R DeVos John N Nkengasong Chunfu Yang Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance. PLoS ONE |
author_facet |
Du-Ping Zheng Margarida Rodrigues Ebi Bile Duc B Nguyen Karidia Diallo Joshua R DeVos John N Nkengasong Chunfu Yang |
author_sort |
Du-Ping Zheng |
title |
Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance. |
title_short |
Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance. |
title_full |
Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance. |
title_fullStr |
Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance. |
title_full_unstemmed |
Molecular characterization of ambiguous mutations in HIV-1 polymerase gene: implications for monitoring HIV infection status and drug resistance. |
title_sort |
molecular characterization of ambiguous mutations in hiv-1 polymerase gene: implications for monitoring hiv infection status and drug resistance. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Detection of recent HIV infections is a prerequisite for reliable estimations of transmitted HIV drug resistance (t-HIVDR) and incidence. However, accurately identifying recent HIV infection is challenging due partially to the limitations of current serological tests. Ambiguous nucleotides are newly emerged mutations in quasispecies, and accumulate by time of viral infection. We utilized ambiguous mutations to establish a measurement for detecting recent HIV infection and monitoring early HIVDR development. Ambiguous nucleotides were extracted from HIV-1 pol-gene sequences in the datasets of recent (HIVDR threshold surveys [HIVDR-TS] in 7 countries; n=416) and established infections (1 HIVDR monitoring survey at baseline; n=271). An ambiguous mutation index of 2.04×10(-3) nts/site was detected in HIV-1 recent infections which is equivalent to the HIV-1 substitution rate (2×10(-3) nts/site/year) reported before. However, significantly higher index (14.41×10(-3) nts/site) was revealed with established infections. Using this substitution rate, 75.2% subjects in HIVDR-TS with the exception of the Vietnam dataset and 3.3% those in HIVDR-baseline were classified as recent infection within one year. We also calculated mutation scores at amino acid level at HIVDR sites based on ambiguous or fitted mutations. The overall mutation scores caused by ambiguous mutations increased (0.54×10(-2)3.48×10(-2)/DR-site) whereas those caused by fitted mutations remained stable (7.50-7.89×10(-2)/DR-site) in both recent and established infections, indicating that t-HIVDR exists in drug-naïve populations regardless of infection status in which new HIVDR continues to emerge. Our findings suggest that characterization of ambiguous mutations in HIV may serve as an additional tool to differentiate recent from established infections and to monitor HIVDR emergence. |
url |
http://europepmc.org/articles/PMC3798419?pdf=render |
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