Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model
Abstract Combination anti-retroviral therapy (cART) has drastically improved the clinical outcome of HIV-1 infection. Nonetheless, despite effective cART, HIV-1 persists indefinitely in infected individuals. Clonal expansion of HIV-1-infected cells in peripheral blood has been reported recently. cAR...
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| Format: | Article |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07307-4 |
| _version_ | 1818840905443966976 |
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| author | Yorifumi Satou Hiroo Katsuya Asami Fukuda Naoko Misawa Jumpei Ito Yoshikazu Uchiyama Paola Miyazato Saiful Islam Ariberto Fassati Anat Melamed Charles R. M. Bangham Yoshio Koyanagi Kei Sato |
| author_facet | Yorifumi Satou Hiroo Katsuya Asami Fukuda Naoko Misawa Jumpei Ito Yoshikazu Uchiyama Paola Miyazato Saiful Islam Ariberto Fassati Anat Melamed Charles R. M. Bangham Yoshio Koyanagi Kei Sato |
| author_sort | Yorifumi Satou |
| collection | DOAJ |
| description | Abstract Combination anti-retroviral therapy (cART) has drastically improved the clinical outcome of HIV-1 infection. Nonetheless, despite effective cART, HIV-1 persists indefinitely in infected individuals. Clonal expansion of HIV-1-infected cells in peripheral blood has been reported recently. cART is effective in stopping the retroviral replication cycle, but not in inhibiting clonal expansion of the infected host cells. Thus, the proliferation of HIV-1-infected cells may play a role in viral persistence, but little is known about the kinetics of the generation, the tissue distribution or the underlying mechanism of clonal expansion in vivo. Here we analyzed the clonality of HIV-1-infected cells using high-throughput integration site analysis in a hematopoietic stem cell-transplanted humanized mouse model. Clonally expanded, HIV-1-infected cells were detectable at two weeks post infection, their abundance increased with time, and certain clones were present in multiple organs. Expansion of HIV-1-infected clones was significantly more frequent when the provirus was integrated near host genes in specific gene ontological classes, including cell activation and chromatin regulation. These results identify potential drivers of clonal expansion of HIV-1-infected cells in vivo. |
| first_indexed | 2024-12-19T04:17:37Z |
| format | Article |
| id | doaj.art-6446353887b2425680ff7c11f4c4b2b3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:17:37Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6446353887b2425680ff7c11f4c4b2b32022-12-21T20:36:15ZengNature PortfolioScientific Reports2045-23222017-07-017111210.1038/s41598-017-07307-4Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse modelYorifumi Satou0Hiroo Katsuya1Asami Fukuda2Naoko Misawa3Jumpei Ito4Yoshikazu Uchiyama5Paola Miyazato6Saiful Islam7Ariberto Fassati8Anat Melamed9Charles R. M. Bangham10Yoshio Koyanagi11Kei Sato12International Research Center for Medical Sciences (IRCMS), Kumamoto UniversityInternational Research Center for Medical Sciences (IRCMS), Kumamoto UniversityInternational Research Center for Medical Sciences (IRCMS), Kumamoto UniversityLaboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto UniversityDivision of Human Genetics, Department of Integrated Genetics, National Institute of GeneticsDepartment of Medical Physics, Faculty of Life Sciences, Kumamoto UniversityInternational Research Center for Medical Sciences (IRCMS), Kumamoto UniversityInternational Research Center for Medical Sciences (IRCMS), Kumamoto UniversityDivision of Infection and Immunity, University College LondonDepartment of Immunology, Division of Infectious Diseases, Imperial College LondonDepartment of Immunology, Division of Infectious Diseases, Imperial College LondonLaboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto UniversityLaboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto UniversityAbstract Combination anti-retroviral therapy (cART) has drastically improved the clinical outcome of HIV-1 infection. Nonetheless, despite effective cART, HIV-1 persists indefinitely in infected individuals. Clonal expansion of HIV-1-infected cells in peripheral blood has been reported recently. cART is effective in stopping the retroviral replication cycle, but not in inhibiting clonal expansion of the infected host cells. Thus, the proliferation of HIV-1-infected cells may play a role in viral persistence, but little is known about the kinetics of the generation, the tissue distribution or the underlying mechanism of clonal expansion in vivo. Here we analyzed the clonality of HIV-1-infected cells using high-throughput integration site analysis in a hematopoietic stem cell-transplanted humanized mouse model. Clonally expanded, HIV-1-infected cells were detectable at two weeks post infection, their abundance increased with time, and certain clones were present in multiple organs. Expansion of HIV-1-infected clones was significantly more frequent when the provirus was integrated near host genes in specific gene ontological classes, including cell activation and chromatin regulation. These results identify potential drivers of clonal expansion of HIV-1-infected cells in vivo.https://doi.org/10.1038/s41598-017-07307-4 |
| spellingShingle | Yorifumi Satou Hiroo Katsuya Asami Fukuda Naoko Misawa Jumpei Ito Yoshikazu Uchiyama Paola Miyazato Saiful Islam Ariberto Fassati Anat Melamed Charles R. M. Bangham Yoshio Koyanagi Kei Sato Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model Scientific Reports |
| title | Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model |
| title_full | Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model |
| title_fullStr | Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model |
| title_full_unstemmed | Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model |
| title_short | Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model |
| title_sort | dynamics and mechanisms of clonal expansion of hiv 1 infected cells in a humanized mouse model |
| url | https://doi.org/10.1038/s41598-017-07307-4 |
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