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Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan
(1) Background: HIV-1 sub-subtype A1 is common in parts of Africa, Russia, former Soviet Union countries, and Eastern Europe. In Pakistan, sub-subtype A1 is the predominant HIV-1 subtype. Preliminary evidence suggests that distinct strains of HIV-1 sub-subtype A1 are circulating in Pakistan; however...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611109/ https://www.ncbi.nlm.nih.gov/pubmed/36298862 http://dx.doi.org/10.3390/v14102307 |
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author | Tariq, Uroosa Nazziwa, Jamirah Sasinovich, Sviataslau Shah, Sharaf Ali Naeem, Sadaf Abidi, Syed Hani Esbjörnsson, Joakim |
author_facet | Tariq, Uroosa Nazziwa, Jamirah Sasinovich, Sviataslau Shah, Sharaf Ali Naeem, Sadaf Abidi, Syed Hani Esbjörnsson, Joakim |
author_sort | Tariq, Uroosa |
collection | PubMed |
description | (1) Background: HIV-1 sub-subtype A1 is common in parts of Africa, Russia, former Soviet Union countries, and Eastern Europe. In Pakistan, sub-subtype A1 is the predominant HIV-1 subtype. Preliminary evidence suggests that distinct strains of HIV-1 sub-subtype A1 are circulating in Pakistan; however, an in-depth molecular phylogenetic characterization of HIV-1 sub-subtype A1 strains in Pakistan have not been presented. We performed a detailed characterization of the HIV-1 sub-subtype A1 epidemic in Pakistan using state-of-the-art molecular epidemiology and phylodynamics. (2) Methods: A total of 143 HIV-1 sub-subtype A1 gag sequences, including 61 sequences generated specifically for this study from PLHIVs part of our cohort, representing all sub-subtype A1 gag sequences from Pakistan, were analyzed. Maximum-likelihood phylogenetic cluster analysis was used to determine the relationship between Pakistani sub-subtype A1 strains and pandemic sub-subtype A1 strains. Furthermore, we used signature variation, charge distribution, selection pressures, and epitope prediction analyses to characterize variations unique to Pakistani HIV-1 strains and establish the association between signature variations and Gag epitope profile. (3) Results: The HIV-1 sub-subtype A1 sequences from Pakistan formed three main clusters: two that clustered with Kenyan sequences (7 and 10 sequences, respectively) and one that formed a Pakistan-specific cluster of 123 sequences that were much less related to other sub-subtype A1 sequences available in the database. The sequences in the Pakistan-specific cluster and the Kenyan reference strains exhibited several signature variations, especially at amino acid positions 312, 319, 331, 372, 373, 383, and 402. Structural protein modeling suggested that amino acid changes in these positions result in alterations of the Gag protein structure as well as in Gag-specific T-cell epitopes. (4) Conclusions: Our results suggest that the majority of the Pakistan HIV-1 sub-subtype A1 strains were unique to Pakistan and with a specific mutation pattern in Gag. |
format | Online Article Text |
id | pubmed-9611109 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96111092022-10-28 Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan Tariq, Uroosa Nazziwa, Jamirah Sasinovich, Sviataslau Shah, Sharaf Ali Naeem, Sadaf Abidi, Syed Hani Esbjörnsson, Joakim Viruses Article (1) Background: HIV-1 sub-subtype A1 is common in parts of Africa, Russia, former Soviet Union countries, and Eastern Europe. In Pakistan, sub-subtype A1 is the predominant HIV-1 subtype. Preliminary evidence suggests that distinct strains of HIV-1 sub-subtype A1 are circulating in Pakistan; however, an in-depth molecular phylogenetic characterization of HIV-1 sub-subtype A1 strains in Pakistan have not been presented. We performed a detailed characterization of the HIV-1 sub-subtype A1 epidemic in Pakistan using state-of-the-art molecular epidemiology and phylodynamics. (2) Methods: A total of 143 HIV-1 sub-subtype A1 gag sequences, including 61 sequences generated specifically for this study from PLHIVs part of our cohort, representing all sub-subtype A1 gag sequences from Pakistan, were analyzed. Maximum-likelihood phylogenetic cluster analysis was used to determine the relationship between Pakistani sub-subtype A1 strains and pandemic sub-subtype A1 strains. Furthermore, we used signature variation, charge distribution, selection pressures, and epitope prediction analyses to characterize variations unique to Pakistani HIV-1 strains and establish the association between signature variations and Gag epitope profile. (3) Results: The HIV-1 sub-subtype A1 sequences from Pakistan formed three main clusters: two that clustered with Kenyan sequences (7 and 10 sequences, respectively) and one that formed a Pakistan-specific cluster of 123 sequences that were much less related to other sub-subtype A1 sequences available in the database. The sequences in the Pakistan-specific cluster and the Kenyan reference strains exhibited several signature variations, especially at amino acid positions 312, 319, 331, 372, 373, 383, and 402. Structural protein modeling suggested that amino acid changes in these positions result in alterations of the Gag protein structure as well as in Gag-specific T-cell epitopes. (4) Conclusions: Our results suggest that the majority of the Pakistan HIV-1 sub-subtype A1 strains were unique to Pakistan and with a specific mutation pattern in Gag. MDPI 2022-10-20 /pmc/articles/PMC9611109/ /pubmed/36298862 http://dx.doi.org/10.3390/v14102307 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tariq, Uroosa Nazziwa, Jamirah Sasinovich, Sviataslau Shah, Sharaf Ali Naeem, Sadaf Abidi, Syed Hani Esbjörnsson, Joakim Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan |
title | Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan |
title_full | Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan |
title_fullStr | Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan |
title_full_unstemmed | Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan |
title_short | Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan |
title_sort | phylogenetic characterization of hiv-1 sub-subtype a1 in karachi, pakistan |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9611109/ https://www.ncbi.nlm.nih.gov/pubmed/36298862 http://dx.doi.org/10.3390/v14102307 |
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