Affiliation:
1. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, Dental Sciences Building Room 3007, London, ON N6A 3K7, Canada
Abstract
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.
Funder
Canadian Institutes of Health Research (CIHR) Operating Grants
Canada Research Chair Tier 1
National Institute of Allergy and Infectious Diseases-National Institutes of Health
Subject
Virology,Infectious Diseases
Cited by
1 articles.
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1. HIV-1 subtypes and latent reservoirs;Current Opinion in HIV and AIDS;2023-12-12