Antiretroviral APOBEC3 Cytidine Deaminases Alter HIV-1 Provirus Integration Site Profiles

Hannah O. Ajoge, Tyler M. Renner, Kasandra Bélanger, Hinissan P. Kohio, Macon D. Coleman, Marc-André Langlois, Stephen D. Barr

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Nov 15, 2019
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Received Date: 11th November 19

APOBEC3 (A3) proteins are host-encoded deoxycytidine deaminases that provide an innate immune barrier to retroviral infection, notably against HIV-1. While the catalytic activity of these proteins can induce catastrophic hypermutation in proviral DNA leading to near-total restriction of infection, sublethal levels of deamination contribute to the genetic evolution of HIV-1. So far, little is known about how A3 might impact HIV-1 integrations into human chromosomal DNA. Using a deep sequencing approach, we analyzed the influence A3F and A3G on HIV-1 integration site selections. DNA editing was detected at the extremities of the long terminal repeat regions of the virus. Both catalytic active and non-catalytic A3 enzymes decreased insertions into gene coding sequences and increased integration sites into SINE elements, oncogenes and transcription-silencing non-B DNA features. Our data implicate A3 as host factors that influence HIV-1 integration site selection and promote insertions into genomic sites that are transcriptionally less active.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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