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Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
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What Integration Sites Tell Us about HIV Persistence
Stephen H Hughes1, John M Coffin2
1HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
Cell Host & Microbe
|May 14, 2016
Summary
Clonally expanded cells in HIV-infected patients can harbor replication-competent viruses. Despite most human immunodeficiency viruses (HIV) being defective, these expanded clones pose challenges for HIV cure strategies.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Technological advancements enable analysis of viral integration sites in human immunodeficiency virus (HIV)-infected cells.
- A substantial proportion of infected cells in patients undergoing long-term HIV therapy exhibit clonal expansion.
- Integrated viral DNA can drive the clonal expansion of HIV-infected cells.
Purpose of the Study:
- To analyze the implications of clonal expansion in HIV-infected cells.
- To understand the role of replication-competent proviruses within expanded clones.
- To assess the impact of these findings on HIV cure strategies.
Main Methods:
- Analysis of viral integration sites in cells from HIV-infected patients.
- Assessment of proviral DNA status (defective vs. replication-competent).
- Evaluation of clonal expansion dynamics in vivo.
Main Results:
- A significant fraction of infected cells in treated patients are clonally expanded.
- Expanded clones can harbor replication-competent human immunodeficiency virus (HIV) proviruses, despite most proviruses being defective (>95%).
- Cells from these clones can release infectious virus, though virus-producing cells are likely selected against in vivo.
Conclusions:
- Expanded clones carrying replication-competent human immunodeficiency virus (HIV) can survive and expand because only a small fraction of cells produce infectious virus.
- These findings highlight the persistence of the HIV reservoir and complicate curative strategies.
- Understanding clonal expansion dynamics is crucial for developing effective HIV eradication therapies.
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