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HIV infection results in clonal expansions containing integrations within pathogenesis-related biological pathways
Kevin G. Haworth, … , Jennifer E. Adair, Hans-Peter Kiem
Kevin G. Haworth, … , Jennifer E. Adair, Hans-Peter Kiem
Published July 12, 2018
Citation Information: JCI Insight. 2018;3(13):e99127. https://doi.org/10.1172/jci.insight.99127.
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Research Article AIDS/HIV Virology

HIV infection results in clonal expansions containing integrations within pathogenesis-related biological pathways

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Abstract

The genomic integration of HIV into cells results in long-term persistence of virally infected cell populations. This integration event acts as a heritable mark that can be tracked to monitor infected cells that persist over time. Previous reports have documented clonal expansion in people and have linked them to proto-oncogenes; however, their significance or contribution to the latent reservoir has remained unclear. Here, we demonstrate that a directed pattern of clonal expansion occurs in vivo, specifically in gene pathways important for viral replication and persistence. These biological processes include cellular division, transcriptional regulation, RNA processing, and posttranslational modification pathways. This indicates preferential expansion when integration events occur within genes or biological pathways beneficial for HIV replication and persistence. Additionally, these expansions occur quickly during unsuppressed viral replication in vivo, reinforcing the importance of early intervention for individuals to limit reservoir seeding of clonally expanded HIV-infected cells.

Authors

Kevin G. Haworth, Lauren E. Schefter, Zachary K. Norgaard, Christina Ironside, Jennifer E. Adair, Hans-Peter Kiem

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