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HIV-1 Integration Landscape during Latent and Active Infection
Open accessAbstract
SUMMARY 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.
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Metadata
- Authors
- Cohn, L. B., Silva, I. T., Oliveira, T. Y., Rosales, R. A., Parrish, E. H., Learn, G. H., Hahn, B. H., Czartoski, J. L., McElrath, M. J., Lehmann, C., Klein, F., Caskey, M., Walker, B. D., Siliciano, J. D., Siliciano, R. F., Jankovic, M., & Nussenzweig, M. C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 160
- Issue
- 3
- Pages
- 420-432
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2169033726
- Cited by
- 444
- References
- 12
- FWCI
- 25.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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