Spatial and Genomic Correlates of HIV-1 Integration Site Targeting.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

HIV-1*/genetics ; HIV-1*/metabolism; Capsid/metabolism ; Capsid Proteins/metabolism ; Chromatin/metabolism ; Host-Pathogen Interactions/genetics ; Virus Integration/genetics

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.

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P30 AI060354 United States AI NIAID NIH HHS; R01 AI052014 United States AI NIAID NIH HHS; T32 AI007386 United States AI NIAID NIH HHS; 5P30AI060354 National Institute of Allergy and Infectious Diseases

Keywords: CPSF6; HIV/AIDS; LEDGF/p75; lamina-associated domains; nuclear speckles; retroviral integration; speckle-associated domains

0 (Capsid Proteins)
0 (Chromatin)

Date Created: 20220225 Date Completed: 20220408 Latest Revision: 20230131

20240628

PMC8869898

10.3390/cells11040655

35203306