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タイトル: Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model
著者: Satou, Yorifumi
Katsuya, Hiroo
Fukuda, Asami
Misawa, Naoko
Ito, Jumpei
Uchiyama, Yoshikazu
Miyazato, Paola
Islam, Saiful
Fassati, Ariberto
Melamed, Anat
Bangham, Charles R. M.
Koyanagi, Yoshio
Sato, Kei
著者名の別形: 三沢, 尚子
小柳, 義夫
佐藤, 佳
キーワード: Pathogens
Retrovirus
Viral reservoirs
Virus–host interactions
発行日: 31-Jul-2017
出版者: Springer Nature
誌名: Scientific Reports
巻: 7
論文番号: 6913
抄録: 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.
著作権等: © The Author(s) 2017.
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
URI: http://hdl.handle.net/2433/227890
DOI(出版社版): 10.1038/s41598-017-07307-4
出現コレクション:学術雑誌掲載論文等

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