Phylogenetic Characterization of HIV-1 Sub-Subtype A1 in Karachi, Pakistan
Tariq U. Nazziwa J. Sasinovich S. Shah S.A. Naeem S. Abidi S.H. Esbjörnsson J.
October 2022MDPI
Viruses
2022#14Issue 10
(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.
epitopes , gag , HIV-1 , Pakistan , phylodynamics , phylogenetics , sub-subtype A1
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Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, 74800, Pakistan
Department of Biochemistry, University of Karachi, Karachi, 75270, Pakistan
Department of Translational Medicine, Lund University, Lund, SE-221 00, Sweden
Bridge Consultants Foundation, Karachi, 75100, Pakistan
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, 010000, Kazakhstan
Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom
Department of Biological and Biomedical Sciences
Department of Biochemistry
Department of Translational Medicine
Bridge Consultants Foundation
Department of Biomedical Sciences
Nuffield Department of Medicine
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