Specialized DNA Structures Act as Genomic Beacons for Integration by Evolutionarily Diverse Retroviruses.
Hinissan P KohioHannah O AjogeMacon D ColemanEmmanuel NdashimyeRichard M GibsonEric J ArtsStephen D BarrPublished in: Viruses (2023)
Retroviral integration site targeting is not random and plays a critical role in expression and long-term survival of the integrated provirus. To better understand the genomic environment surrounding retroviral integration sites, we performed a meta-analysis of previously published integration site data from evolutionarily diverse retroviruses, including new experimental data from HIV-1 subtypes A, B, C and D. We show here that evolutionarily divergent retroviruses exhibit distinct integration site profiles with strong preferences for integration near non-canonical B-form DNA (non-B DNA). We also show that in vivo-derived HIV-1 integration sites are significantly more enriched in transcriptionally silent regions and transcription-silencing non-B DNA features of the genome compared to in vitro-derived HIV-1 integration sites. Integration sites from individuals infected with HIV-1 subtype A, B, C or D viruses exhibited different preferences for common genomic and non-B DNA features. In addition, we identified several integration site hotspots shared between different HIV-1 subtypes, all of which were located in the non-B DNA feature slipped DNA. Together, these data show that although evolutionarily divergent retroviruses exhibit distinct integration site profiles, they all target non-B DNA for integration. These findings provide new insight into how retroviruses integrate into genomes for long-term survival.
Keyphrases
- circulating tumor
- antiretroviral therapy
- cell free
- hiv infected
- single molecule
- hiv positive
- human immunodeficiency virus
- hepatitis c virus
- hiv testing
- hiv aids
- gene expression
- electronic health record
- machine learning
- nucleic acid
- big data
- systematic review
- transcription factor
- poor prognosis
- deep learning
- long non coding rna
- dna methylation
- meta analyses