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New Insights in the Fight against HIV
Article

Spatial and Genomic Correlates of HIV-1 Integration Site Targeting

1
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
2
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Mara Biasin
Cells 2022, 11(4), 655; https://doi.org/10.3390/cells11040655
Received: 24 January 2022 / Accepted: 10 February 2022 / Published: 14 February 2022
(This article belongs to the Special Issue HIV and Host Interactions)
HIV-1 integrase and capsid proteins interact with host proteins to direct preintegration complexes to active transcription units within gene-dense regions of chromosomes for viral DNA integration. Analyses of spatially-derived genomic DNA coordinates, such as nuclear speckle-associated domains, lamina-associated domains, super enhancers, and Spatial Position Inference of the Nuclear (SPIN) genome states, have further informed the mechanisms of HIV-1 integration targeting. Critically, however, these different types of genomic coordinates have not been systematically analyzed to synthesize a concise description of the regions of chromatin that HIV-1 prefers for integration. To address this informational gap, we have extensively correlated genomic DNA coordinates of HIV-1 integration targeting preferences. We demonstrate that nuclear speckle-associated and speckle-proximal chromatin are highly predictive markers of integration and that these regions account for known HIV biases for gene-dense regions, highly transcribed genes, as well as the mid-regions of gene bodies. In contrast to a prior report that intronless genes were poorly targeted for integration, we find that intronless genes in proximity to nuclear speckles are more highly targeted than are spatially-matched intron-containing genes. Our results additionally highlight the contributions of capsid and integrase interactions with respective CPSF6 and LEDGF/p75 host factors in these HIV-1 integration targeting preferences. View Full-Text
Keywords: HIV/AIDS; retroviral integration; nuclear speckles; speckle-associated domains; lamina-associated domains; LEDGF/p75; CPSF6 HIV/AIDS; retroviral integration; nuclear speckles; speckle-associated domains; lamina-associated domains; LEDGF/p75; CPSF6
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MDPI and ACS Style

Singh, P.K.; Bedwell, G.J.; Engelman, A.N. Spatial and Genomic Correlates of HIV-1 Integration Site Targeting. Cells 2022, 11, 655. https://doi.org/10.3390/cells11040655

AMA Style

Singh PK, Bedwell GJ, Engelman AN. Spatial and Genomic Correlates of HIV-1 Integration Site Targeting. Cells. 2022; 11(4):655. https://doi.org/10.3390/cells11040655

Chicago/Turabian Style

Singh, Parmit K., Gregory J. Bedwell, and Alan N. Engelman. 2022. "Spatial and Genomic Correlates of HIV-1 Integration Site Targeting" Cells 11, no. 4: 655. https://doi.org/10.3390/cells11040655

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