Bedwell, GregoryEngelman, AlanSingh, Parmit2022-02-172022-02-14Singh, Parmit, Gregory Bedwell, Alan Engelman. "Spatial and Genomic Correlates of HIV-1 Integration Site Targeting." Cells 11, no. 4 (2022): 655. DOI: 10.3390/cells110406552073-4409https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37370827HIV-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.en-USGeneral MedicineHIV/AIDSretroviral integrationnuclear specklesspeckle-associated domainslamina-associated domainsLEDGF/p75CPSF6Journal Article2022-02-1710.3390/cells11040655