HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection
A series of HIV-1 CRF01_AE/CRF07_BC recombinants were previously found to have emerged gradually in a superinfected patient (patient LNA819). However, the extent to which T-cell responses influenced the development of these recombinants after superinfection is unclear. In this study, we undertook a...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.820628/full |
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| author | Hui Zhang Hui Zhang Hui Zhang Shuang Cao Shuang Cao Shuang Cao Shuang Cao Yang Gao Yang Gao Yang Gao Xiao Sun Xiao Sun Xiao Sun Fanming Jiang Fanming Jiang Fanming Jiang Bin Zhao Bin Zhao Bin Zhao Haibo Ding Haibo Ding Haibo Ding Tao Dong Tao Dong Xiaoxu Han Xiaoxu Han Xiaoxu Han Hong Shang Hong Shang Hong Shang Hong Shang |
| author_facet | Hui Zhang Hui Zhang Hui Zhang Shuang Cao Shuang Cao Shuang Cao Shuang Cao Yang Gao Yang Gao Yang Gao Xiao Sun Xiao Sun Xiao Sun Fanming Jiang Fanming Jiang Fanming Jiang Bin Zhao Bin Zhao Bin Zhao Haibo Ding Haibo Ding Haibo Ding Tao Dong Tao Dong Xiaoxu Han Xiaoxu Han Xiaoxu Han Hong Shang Hong Shang Hong Shang Hong Shang |
| author_sort | Hui Zhang |
| collection | DOAJ |
| description | A series of HIV-1 CRF01_AE/CRF07_BC recombinants were previously found to have emerged gradually in a superinfected patient (patient LNA819). However, the extent to which T-cell responses influenced the development of these recombinants after superinfection is unclear. In this study, we undertook a recombination structure analysis of the gag, pol, and nef genes from longitudinal samples of patient LNA819. A total of 9 pol and 5 nef CRF01_AE/CRF07_BC recombinants were detected. The quasispecies makeup and the composition of the pol and nef gene recombinants changed continuously, suggestive of continuous evolution in vivo. T-cell responses targeting peptides of the primary strain and the recombination regions were screened. The results showed that Pol-LY10, Pol-RY9, and Nef-GL9 were the immunodominant epitopes. Pol-LY10 overlapped with the recombination breakpoints in multiple recombinants. For the LY10 epitope, escape from T-cell responses was mediated by both recombination with a CRF07_BC insertion carrying the T467E/T472V variants and T467N/T472V mutations originating in the CRF01_AE strain. In pol recombinants R8 and R9, the recombination breakpoints were located ~23 amino acids upstream of the RY9 epitope. The appearance of new recombination breakpoints harboring a CRF07_BC insertion carrying a R984K variant was associated with escape from RY9-specific T-cell responses. Although the Nef-GL9 epitope was located either within or 10~11 amino acids downstream of the recombination breakpoints, no variant of this epitope was observed in the nef recombinants. Instead, a F85V mutation originating in the CRF01_AE strain was the main immune escape mechanism. Understanding the cellular immune pressure on recombination is critical for monitoring the new circulating recombinant forms of HIV and designing epitope-based vaccines. Vaccines targeting antigens that are less likely to escape immune pressure by recombination and/or mutation are likely to be of benefit to patients with HIV-1. |
| first_indexed | 2024-12-20T13:25:04Z |
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| language | English |
| last_indexed | 2024-12-20T13:25:04Z |
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| spelling | doaj.art-baf443019e6241f79abd8edf4ab6d3802022-12-21T19:39:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.820628820628HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following SuperinfectionHui Zhang0Hui Zhang1Hui Zhang2Shuang Cao3Shuang Cao4Shuang Cao5Shuang Cao6Yang Gao7Yang Gao8Yang Gao9Xiao Sun10Xiao Sun11Xiao Sun12Fanming Jiang13Fanming Jiang14Fanming Jiang15Bin Zhao16Bin Zhao17Bin Zhao18Haibo Ding19Haibo Ding20Haibo Ding21Tao Dong22Tao Dong23Xiaoxu Han24Xiaoxu Han25Xiaoxu Han26Hong Shang27Hong Shang28Hong Shang29Hong Shang30National Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaNational Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaClinical Laboratory, China Medical University Shengjing Hospital Nanhu Branch, Shenyang, ChinaNational Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaNational Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaNational Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaNational Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaNational Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaChinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, Oxford University, Oxford, United KingdomMedical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford, United KingdomNational Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaNational Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, ChinaKey Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, ChinaKey Laboratory of AIDS Immunology of Liaoning Province, Shenyang, ChinaChinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, Oxford University, Oxford, United KingdomA series of HIV-1 CRF01_AE/CRF07_BC recombinants were previously found to have emerged gradually in a superinfected patient (patient LNA819). However, the extent to which T-cell responses influenced the development of these recombinants after superinfection is unclear. In this study, we undertook a recombination structure analysis of the gag, pol, and nef genes from longitudinal samples of patient LNA819. A total of 9 pol and 5 nef CRF01_AE/CRF07_BC recombinants were detected. The quasispecies makeup and the composition of the pol and nef gene recombinants changed continuously, suggestive of continuous evolution in vivo. T-cell responses targeting peptides of the primary strain and the recombination regions were screened. The results showed that Pol-LY10, Pol-RY9, and Nef-GL9 were the immunodominant epitopes. Pol-LY10 overlapped with the recombination breakpoints in multiple recombinants. For the LY10 epitope, escape from T-cell responses was mediated by both recombination with a CRF07_BC insertion carrying the T467E/T472V variants and T467N/T472V mutations originating in the CRF01_AE strain. In pol recombinants R8 and R9, the recombination breakpoints were located ~23 amino acids upstream of the RY9 epitope. The appearance of new recombination breakpoints harboring a CRF07_BC insertion carrying a R984K variant was associated with escape from RY9-specific T-cell responses. Although the Nef-GL9 epitope was located either within or 10~11 amino acids downstream of the recombination breakpoints, no variant of this epitope was observed in the nef recombinants. Instead, a F85V mutation originating in the CRF01_AE strain was the main immune escape mechanism. Understanding the cellular immune pressure on recombination is critical for monitoring the new circulating recombinant forms of HIV and designing epitope-based vaccines. Vaccines targeting antigens that are less likely to escape immune pressure by recombination and/or mutation are likely to be of benefit to patients with HIV-1.https://www.frontiersin.org/articles/10.3389/fimmu.2021.820628/fullHIV-1recombinationbreak pointsT cell responsesescape mutation |
| spellingShingle | Hui Zhang Hui Zhang Hui Zhang Shuang Cao Shuang Cao Shuang Cao Shuang Cao Yang Gao Yang Gao Yang Gao Xiao Sun Xiao Sun Xiao Sun Fanming Jiang Fanming Jiang Fanming Jiang Bin Zhao Bin Zhao Bin Zhao Haibo Ding Haibo Ding Haibo Ding Tao Dong Tao Dong Xiaoxu Han Xiaoxu Han Xiaoxu Han Hong Shang Hong Shang Hong Shang Hong Shang HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection Frontiers in Immunology HIV-1 recombination break points T cell responses escape mutation |
| title | HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection |
| title_full | HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection |
| title_fullStr | HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection |
| title_full_unstemmed | HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection |
| title_short | HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection |
| title_sort | hiv 1 specific immunodominant t cell responses drive the dynamics of hiv 1 recombination following superinfection |
| topic | HIV-1 recombination break points T cell responses escape mutation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.820628/full |
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