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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6446353887b2425680ff7c11f4c4b2b3
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spelling	oai:doaj.org-article:6446353887b2425680ff7c11f4c4b2b32021-12-02T11:52:21ZDynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model10.1038/s41598-017-07307-42045-2322https://doaj.org/article/6446353887b2425680ff7c11f4c4b2b32017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07307-4https://doaj.org/toc/2045-2322Abstract 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.Yorifumi SatouHiroo KatsuyaAsami FukudaNaoko MisawaJumpei ItoYoshikazu UchiyamaPaola MiyazatoSaiful IslamAriberto FassatiAnat MelamedCharles R. M. BanghamYoshio KoyanagiKei SatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	dynamics and mechanisms of clonal expansion of hiv-1-infected cells in a humanized mouse model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6446353887b2425680ff7c11f4c4b2b3
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Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model

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