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The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa

BACKGROUND: HIV-1 subtype C demonstrates several biological properties distinct from other viral subtypes. One such variation is the duplication of PTAP motif in p6 Gag. PTAP motif is a key player in viral budding. Here, we studied the prevalence of PTAP motif duplication in subtype C viral strains...

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Autores principales: Sharma, Shilpee, Aralaguppe, Shambhu G., Abrahams, Melissa-Rose, Williamson, Carolyn, Gray, Clive, Balakrishnan, Pachamuthu, Saravanan, Shanmugam, Murugavel, Kailapuri G., Solomon, Suniti, Ranga, Udaykumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259826/
https://www.ncbi.nlm.nih.gov/pubmed/28118816
http://dx.doi.org/10.1186/s12879-017-2184-4
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author Sharma, Shilpee
Aralaguppe, Shambhu G.
Abrahams, Melissa-Rose
Williamson, Carolyn
Gray, Clive
Balakrishnan, Pachamuthu
Saravanan, Shanmugam
Murugavel, Kailapuri G.
Solomon, Suniti
Ranga, Udaykumar
author_facet Sharma, Shilpee
Aralaguppe, Shambhu G.
Abrahams, Melissa-Rose
Williamson, Carolyn
Gray, Clive
Balakrishnan, Pachamuthu
Saravanan, Shanmugam
Murugavel, Kailapuri G.
Solomon, Suniti
Ranga, Udaykumar
author_sort Sharma, Shilpee
collection PubMed
description BACKGROUND: HIV-1 subtype C demonstrates several biological properties distinct from other viral subtypes. One such variation is the duplication of PTAP motif in p6 Gag. PTAP motif is a key player in viral budding. Here, we studied the prevalence of PTAP motif duplication in subtype C viral strains in a longitudinal study. METHODS: In a prospective follow-up study, 65 HIV-1 seropositive drug-naive subjects were monitored in two different clinical cohorts of India for 2 years with repeated sampling at 6-month intervals. The viral RNA was extracted from plasma, the gag segment was amplified and sequenced. From a subset of viral isolates the sequences of pol, env and LTR were sequenced. Using HIV-1 gag amino acid sequences available from public databases and additional sequences derived from the Indian and South-African cohorts, we examined the nature of PTAP motif duplication in subtype C. RESULTS: In 16% (8 of 50) of the primary viral strains of India, we identified a sequence duplication of the PTAP motif in Gag p6. The length of the sequence duplication varied from 6 to 14 amino acids in the viral isolates but remained fixed within a subject over a period of 24–36 month follow-up. In the duplicated motif, the core PTAP motif was invariable, but the flanking residues were highly variable. In an acute phase clinical cohort of South Africa, in a subset of 75 subjects, we found the presence of the PTAP duplication at a frequency of 29.3%. An analysis of the gag sequences from the extant databases showed that unlike other subtypes of HIV-1, subtype C has a natural propensity to generate the PTAP motif duplication at a significantly higher frequency and of greater length. Additionally, the global prevalence of PTAP duplication in subtype C appears to be increasing progressively over the past 30 years. CONCLUSION: We showed that in subtype C, the duplication of the PTAP motif in p6 Gag involves sequence stretches of greater length, and at a much higher frequency as compared to other HIV-1 subtypes. Given that subtype C naturally lacks the Alix binding motif, the acquisition of an additional PTAP motif may confer replication advantage on this HIV-1 subtype. Further investigation is warranted to examine the significance of PTAP motif duplication on the replicative fitness of HIV-1.
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spelling pubmed-52598262017-01-26 The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa Sharma, Shilpee Aralaguppe, Shambhu G. Abrahams, Melissa-Rose Williamson, Carolyn Gray, Clive Balakrishnan, Pachamuthu Saravanan, Shanmugam Murugavel, Kailapuri G. Solomon, Suniti Ranga, Udaykumar BMC Infect Dis Research Article BACKGROUND: HIV-1 subtype C demonstrates several biological properties distinct from other viral subtypes. One such variation is the duplication of PTAP motif in p6 Gag. PTAP motif is a key player in viral budding. Here, we studied the prevalence of PTAP motif duplication in subtype C viral strains in a longitudinal study. METHODS: In a prospective follow-up study, 65 HIV-1 seropositive drug-naive subjects were monitored in two different clinical cohorts of India for 2 years with repeated sampling at 6-month intervals. The viral RNA was extracted from plasma, the gag segment was amplified and sequenced. From a subset of viral isolates the sequences of pol, env and LTR were sequenced. Using HIV-1 gag amino acid sequences available from public databases and additional sequences derived from the Indian and South-African cohorts, we examined the nature of PTAP motif duplication in subtype C. RESULTS: In 16% (8 of 50) of the primary viral strains of India, we identified a sequence duplication of the PTAP motif in Gag p6. The length of the sequence duplication varied from 6 to 14 amino acids in the viral isolates but remained fixed within a subject over a period of 24–36 month follow-up. In the duplicated motif, the core PTAP motif was invariable, but the flanking residues were highly variable. In an acute phase clinical cohort of South Africa, in a subset of 75 subjects, we found the presence of the PTAP duplication at a frequency of 29.3%. An analysis of the gag sequences from the extant databases showed that unlike other subtypes of HIV-1, subtype C has a natural propensity to generate the PTAP motif duplication at a significantly higher frequency and of greater length. Additionally, the global prevalence of PTAP duplication in subtype C appears to be increasing progressively over the past 30 years. CONCLUSION: We showed that in subtype C, the duplication of the PTAP motif in p6 Gag involves sequence stretches of greater length, and at a much higher frequency as compared to other HIV-1 subtypes. Given that subtype C naturally lacks the Alix binding motif, the acquisition of an additional PTAP motif may confer replication advantage on this HIV-1 subtype. Further investigation is warranted to examine the significance of PTAP motif duplication on the replicative fitness of HIV-1. BioMed Central 2017-01-24 /pmc/articles/PMC5259826/ /pubmed/28118816 http://dx.doi.org/10.1186/s12879-017-2184-4 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Sharma, Shilpee
Aralaguppe, Shambhu G.
Abrahams, Melissa-Rose
Williamson, Carolyn
Gray, Clive
Balakrishnan, Pachamuthu
Saravanan, Shanmugam
Murugavel, Kailapuri G.
Solomon, Suniti
Ranga, Udaykumar
The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa
title The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa
title_full The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa
title_fullStr The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa
title_full_unstemmed The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa
title_short The PTAP sequence duplication in HIV-1 subtype C Gag p6 in drug-naive subjects of India and South Africa
title_sort ptap sequence duplication in hiv-1 subtype c gag p6 in drug-naive subjects of india and south africa
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259826/
https://www.ncbi.nlm.nih.gov/pubmed/28118816
http://dx.doi.org/10.1186/s12879-017-2184-4
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