Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa
Abstract Background The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BioMed Central
2021
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| Online Access: | https://hdl.handle.net/1721.1/136826 |
| _version_ | 1826197781850619904 |
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| author | Farinre, Omotayo Gounder, Kamini Reddy, Tarylee Tongo, Marcel Hare, Jonathan Chaplin, Beth Gilmour, Jill Kanki, Phyllis Mann, Jaclyn K Ndung’u, Thumbi |
| author2 | Ragon Institute of MGH, MIT and Harvard |
| author_facet | Ragon Institute of MGH, MIT and Harvard Farinre, Omotayo Gounder, Kamini Reddy, Tarylee Tongo, Marcel Hare, Jonathan Chaplin, Beth Gilmour, Jill Kanki, Phyllis Mann, Jaclyn K Ndung’u, Thumbi |
| author_sort | Farinre, Omotayo |
| collection | MIT |
| description | Abstract
Background
The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower.
Results
Gag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02_AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa.
Conclusions
Although prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02_AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02_AG and subtype A respectively, which may have relevance for vaccine strategies. |
| first_indexed | 2024-09-23T10:53:22Z |
| format | Article |
| id | mit-1721.1/136826 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:53:22Z |
| publishDate | 2021 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1368262023-09-15T18:44:44Z Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa Farinre, Omotayo Gounder, Kamini Reddy, Tarylee Tongo, Marcel Hare, Jonathan Chaplin, Beth Gilmour, Jill Kanki, Phyllis Mann, Jaclyn K Ndung’u, Thumbi Ragon Institute of MGH, MIT and Harvard Abstract Background The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower. Results Gag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02_AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02_AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa. Conclusions Although prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02_AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02_AG and subtype A respectively, which may have relevance for vaccine strategies. 2021-11-01T14:33:37Z 2021-11-01T14:33:37Z 2021-05-05 2021-05-09T03:13:37Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136826 Retrovirology. 2021 May 05;18(1):11 PUBLISHER_CC en https://doi.org/10.1186/s12977-021-00554-4 Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf BioMed Central BioMed Central |
| spellingShingle | Farinre, Omotayo Gounder, Kamini Reddy, Tarylee Tongo, Marcel Hare, Jonathan Chaplin, Beth Gilmour, Jill Kanki, Phyllis Mann, Jaclyn K Ndung’u, Thumbi Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa |
| title | Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa |
| title_full | Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa |
| title_fullStr | Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa |
| title_full_unstemmed | Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa |
| title_short | Subtype-specific differences in Gag-protease replication capacity of HIV-1 isolates from East and West Africa |
| title_sort | subtype specific differences in gag protease replication capacity of hiv 1 isolates from east and west africa |
| url | https://hdl.handle.net/1721.1/136826 |
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