Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity
Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen. Recently, a chr...
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| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01096/full |
| _version_ | 1818517199768256512 |
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| author | Dai Zhang Dai Zhang Sen Zou Yuanyuan Hu Jiali Hou Xintao Hu Li Ren Liying Ma Xiang He Yiming Shao Kunxue Hong |
| author_facet | Dai Zhang Dai Zhang Sen Zou Yuanyuan Hu Jiali Hou Xintao Hu Li Ren Liying Ma Xiang He Yiming Shao Kunxue Hong |
| author_sort | Dai Zhang |
| collection | DOAJ |
| description | Exploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen. Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient. In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor. Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database). Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database. A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies. The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites. Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies. For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses. |
| first_indexed | 2024-12-11T00:52:58Z |
| format | Article |
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| language | English |
| last_indexed | 2024-12-11T00:52:58Z |
| publishDate | 2019-05-01 |
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| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-85313d8705fa4e6aacf6c4def3272b322022-12-22T01:26:35ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-05-011010.3389/fmicb.2019.01096439719Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing ActivityDai Zhang0Dai Zhang1Sen Zou2Yuanyuan Hu3Jiali Hou4Xintao Hu5Li Ren6Liying Ma7Xiang He8Yiming Shao9Kunxue Hong10State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaThe First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaGuangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaState Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing, ChinaExploring the characteristics of the HIV-1 envelope glycoprotein (env) gene in a natural HIV-1 infected individual, with broadly neutralizing activity, may provide insight into the generation of such broadly neutralizing antibodies and initiate the design of an appropriate immunogen. Recently, a chronically HIV-1 infected patient with broadly neutralization activity was identified and a VRC01-class neutralizing antibody DRVIA7 (A7) was isolated from the patient. In the present study, 155 full length HIV-1 env gene fragments (including 68 functionally Env clones) were amplified longitudinally from the plasma of six time points spanning over 5 years in this donor. Viral features were analyzed by comparing Env clones of different time points, as well as 165 Chinese HIV-1 subtype B env sequences from HIV Sequence Database (Chinese B_database). Shorter V1 length, less potential glycan and a lower ratio of NXT: NXS in gp160 were observed in the first five time points compared to that from the last time points, as well that from the Chinese B_database. A sequence analysis and a neutralization assay of Env-pseudoviruses showed that the increasing diversity of env sequences in the patient was consistent with the appearance and maturation of A7 lineage antibodies. The potent neutralization activity and viruses that escaped from the neutralization of the concurrent autologous plasma, are consistent with higher residue variations at the antibody recognition sites. Almost all viruses from the plasmas were neutralization-resistant to VRC01 and A7 lineage antibodies. For a chronically HIV-1 infected individual over 10 years, we found that greater viral diversity, short V1 sequences and less potential N-linked glycosylation (PNGS) in V1, might be associated with the development of broadly neutralizing antibody responses.https://www.frontiersin.org/article/10.3389/fmicb.2019.01096/fullHIV-1envelope genebroadly neutralizing antibodiesglycosylationdiversity |
| spellingShingle | Dai Zhang Dai Zhang Sen Zou Yuanyuan Hu Jiali Hou Xintao Hu Li Ren Liying Ma Xiang He Yiming Shao Kunxue Hong Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity Frontiers in Microbiology HIV-1 envelope gene broadly neutralizing antibodies glycosylation diversity |
| title | Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity |
| title_full | Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity |
| title_fullStr | Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity |
| title_full_unstemmed | Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity |
| title_short | Characteristics of Envelope Genes in a Chinese Chronically HIV-1 Infected Patient With Broadly Neutralizing Activity |
| title_sort | characteristics of envelope genes in a chinese chronically hiv 1 infected patient with broadly neutralizing activity |
| topic | HIV-1 envelope gene broadly neutralizing antibodies glycosylation diversity |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01096/full |
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