HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s
ABSTRACTKnowledge of HIV-1 global sequence diversity is critical for developing an effective prophylactic against HIV-1 infection. We developed the Hervé platform to analyze and visualize trends in HIV-1 diversification. Using Hervé, we analyzed 4,830 Env, 4,407 Gag, and 3,002 Pol publicly available...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2024-03-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.01749-23 |
| _version_ | 1797263239178878976 |
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| author | Eric Lewitus Yifan Li Hongjun Bai Phuc Pham Morgane Rolland |
| author_facet | Eric Lewitus Yifan Li Hongjun Bai Phuc Pham Morgane Rolland |
| author_sort | Eric Lewitus |
| collection | DOAJ |
| description | ABSTRACTKnowledge of HIV-1 global sequence diversity is critical for developing an effective prophylactic against HIV-1 infection. We developed the Hervé platform to analyze and visualize trends in HIV-1 diversification. Using Hervé, we analyzed 4,830 Env, 4,407 Gag, and 3,002 Pol publicly available independent sequences corresponding to subtypes A1, A6, B, C, D, F1, and G and circulating recombinant forms (CRFs) 01_AE, 02_AG, and 07_BC; sequences were sampled between 1980 and 2020 from 82 countries. HIV-1 diversified with a median of 1.82 amino acid substitutions per year in Env, 0.297 in Gag, and 0.779 in Pol. Yet, Env subtype B diversification plateaued post-2000. Pairwise diversity within subtypes and CRFs increased by 41.82% (range = 24.85%–54.41%) in Env, 56.93% (15.38%–89.16%) in Gag, and 46.12% (11.70%–70.57%) in Pol. Consensus sequences based on sequences sampled in each decade remained relatively stable over time. Similarly, at antibody epitope sites, only 0–8 residues that were minority variants became consensus over time in any subtype/CRF and only one known drug resistance mutation site differed from the reference (subtype G). The apparent contradiction between the fast diversification of HIV-1 and its limited adaptation illustrates that HIV-1 evolution is not directional and its consensus is at the intersection of millions of within-host selective processes occurring in a star-like manner. While a consensus sequence is a better representation of HIV-1 diversity than any individual sequence, consensus sequences have progressively become more distant from the circulating sequences they represent.IMPORTANCEGlobal surveillance of HIV-1 sequences is critical for designing relevant prophylactic and therapeutic interventions to infection. We designed an open-source platform, Hervé, for analyzing and visualizing the diversification dynamics of HIV-1 protein sequences. We characterized the evolution of over 12,000 HIV-1 Env, Gag, and Pol protein sequences from 1980–2020 and found that, despite a steady increase in intra-subtype and circulating recombinant form diversity, the most frequent residue at each site, i.e., the consensus, has varied only moderately. |
| first_indexed | 2024-04-25T00:09:51Z |
| format | Article |
| id | doaj.art-19da86c1524a4de884cc71ee43da7502 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-25T00:09:51Z |
| publishDate | 2024-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-19da86c1524a4de884cc71ee43da75022024-03-13T14:01:05ZengAmerican Society for MicrobiologymBio2150-75112024-03-0115310.1128/mbio.01749-23HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980sEric Lewitus0Yifan Li1Hongjun Bai2Phuc Pham3Morgane Rolland4U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USAU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USAABSTRACTKnowledge of HIV-1 global sequence diversity is critical for developing an effective prophylactic against HIV-1 infection. We developed the Hervé platform to analyze and visualize trends in HIV-1 diversification. Using Hervé, we analyzed 4,830 Env, 4,407 Gag, and 3,002 Pol publicly available independent sequences corresponding to subtypes A1, A6, B, C, D, F1, and G and circulating recombinant forms (CRFs) 01_AE, 02_AG, and 07_BC; sequences were sampled between 1980 and 2020 from 82 countries. HIV-1 diversified with a median of 1.82 amino acid substitutions per year in Env, 0.297 in Gag, and 0.779 in Pol. Yet, Env subtype B diversification plateaued post-2000. Pairwise diversity within subtypes and CRFs increased by 41.82% (range = 24.85%–54.41%) in Env, 56.93% (15.38%–89.16%) in Gag, and 46.12% (11.70%–70.57%) in Pol. Consensus sequences based on sequences sampled in each decade remained relatively stable over time. Similarly, at antibody epitope sites, only 0–8 residues that were minority variants became consensus over time in any subtype/CRF and only one known drug resistance mutation site differed from the reference (subtype G). The apparent contradiction between the fast diversification of HIV-1 and its limited adaptation illustrates that HIV-1 evolution is not directional and its consensus is at the intersection of millions of within-host selective processes occurring in a star-like manner. While a consensus sequence is a better representation of HIV-1 diversity than any individual sequence, consensus sequences have progressively become more distant from the circulating sequences they represent.IMPORTANCEGlobal surveillance of HIV-1 sequences is critical for designing relevant prophylactic and therapeutic interventions to infection. We designed an open-source platform, Hervé, for analyzing and visualizing the diversification dynamics of HIV-1 protein sequences. We characterized the evolution of over 12,000 HIV-1 Env, Gag, and Pol protein sequences from 1980–2020 and found that, despite a steady increase in intra-subtype and circulating recombinant form diversity, the most frequent residue at each site, i.e., the consensus, has varied only moderately.https://journals.asm.org/doi/10.1128/mbio.01749-23HIV-1evolutiondiversity |
| spellingShingle | Eric Lewitus Yifan Li Hongjun Bai Phuc Pham Morgane Rolland HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s mBio HIV-1 evolution diversity |
| title | HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s |
| title_full | HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s |
| title_fullStr | HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s |
| title_full_unstemmed | HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s |
| title_short | HIV-1 Gag, Pol, and Env diversified with limited adaptation since the 1980s |
| title_sort | hiv 1 gag pol and env diversified with limited adaptation since the 1980s |
| topic | HIV-1 evolution diversity |
| url | https://journals.asm.org/doi/10.1128/mbio.01749-23 |
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