Satou, Y;
Katsuya, H;
Fukuda, A;
Misawa, N;
Ito, J;
Uchiyama, Y;
Miyazato, P;
... Sato, K; + view all
(2017)
Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model.
Scientific Reports
, 7
, Article 6913. 10.1038/s41598-017-07307-4.
Preview |
Text (Published article)
Satou_Dynamics_mechanisms_clonal.pdf - Published Version Download (2MB) | Preview |
Preview |
Text (Supplementary information)
Satou_Dynamics_mechanisms_clonal_Suppl.pdf Download (899kB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-017-07307-4 |
| Publisher version: | http://dx.doi.org/10.1038/s41598-017-07307-4 |
| Language: | English |
| Additional information: | Open Access: 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. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1570144 |
Loading...
Loading...Loading...Loading...Archive Staff Only
 |
View Item |
