Universität zu Köln

Cohn, Lillian B., Silva, Israel T., Oliveira, Thiago Y., Rosales, Rafael A., Parrish, Erica H., Learn, Gerald H., Hahn, Beatrice H., Czartoski, Julie L., McElrath, M. Juliana, Lehmann, Clara ORCID: 0000-0002-7042-1578, Klein, Florian, Caskey, Marina ORCID: 0000-0003-1727-8693, Walker, Bruce D., Siliciano, Janet D., Siliciano, Robert F., Jankovic, Mila and Nussenzweig, Michel C. (2015). HIV-1 Integration Landscape during Latent and Active Infection. Cell, 160 (3). S. 420 - 433. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

The barrier to curing HIV-1 is thought to reside primarily in CD4(+) T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4(+) T cells that remain relatively quiescent.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cohn, Lillian B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Silva, Israel T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oliveira, Thiago Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosales, Rafael A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Parrish, Erica H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Learn, Gerald H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahn, Beatrice H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Czartoski, Julie L. UNSPECIFIED UNSPECIFIED UNSPECIFIED McElrath, M. Juliana UNSPECIFIED UNSPECIFIED UNSPECIFIED Lehmann, Clara UNSPECIFIED orcid.org/0000-0002-7042-1578 UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Caskey, Marina UNSPECIFIED orcid.org/0000-0003-1727-8693 UNSPECIFIED Walker, Bruce D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Siliciano, Janet D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Siliciano, Robert F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jankovic, Mila UNSPECIFIED UNSPECIFIED UNSPECIFIED Nussenzweig, Michel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-414278
DOI:	10.1016/j.cell.2015.01.020
Journal or Publication Title:	Cell
Volume:	160
Number:	3
Page Range:	S. 420 - 433
Date:	2015
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4172
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; SEQUENCING REVEALS; SITES; PERSISTENCE; RESERVOIR; GENES; PROLIFERATION; VIRUS; IDENTIFICATION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41427