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| Status |
Public on Jan 19, 2016 |
| Title |
Diverse fates of uracilated HIV DNA during infection of myeloid lineage cells |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
Using novel methods for mapping U/A base pairs in HIV DNA, we find that HIV proviruses within infected monocytes and macrophages contain high levels of U/A base pairs arising from the high levels of dUTP present during reverse transcription in these cells. Although U/A pairs retain the coding information of T/A pairs, they are the substrate for the nuclear uracil base excision repair (UBER) machinery that effectively degrades most of the uracilated viral DNA at the pre-integration stage of infection. Uracilated proviruses that successfully integrate either retain the uracils, undergo U/A T/A repair, or experience catastrophic mutagenesis induced by cytokine stimulated error-prone repair. Uracil is abundant in proviruses isolated from genomic DNA of short-lived blood monocytes, but not T cells, of HIV infected blood donors who show complete drug suppression plasma virus. This suggests that monocytes are recently infected by coming into contact with persistent virus producing cells in one or more tissue reservoirs.
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| Overall design |
Data for HIV lockdown of Illumina libraries of MDM cells post viral infection with and without UDG treatment.
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| Contributor(s) |
Hesselberth JR |
| Citation(s) |
27644592 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI124777 |
Fate of Invisible U/A Base Pairs Within HIV DNA in Myeloid Phagocytic Cells |
JOHNS HOPKINS UNIVERSITY |
Stivers |
| R21 AI112351 |
Persistence and Fate of Invisible U/A Pairs in HIV-1 Proviral DNA |
JOHNS HOPKINS UNIVERSITY |
Stivers |
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| |
| Submission date |
Dec 17, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Jay R. Hesselberth |
| E-mail(s) |
jay.hesselberth@cuanschutz.edu
|
| Organization name |
University of Colorado School of Medicine
|
| Department |
Biochemistry and Molecular Gentetics
|
| Lab |
Jay Hesselberth
|
| Street address |
12801 E 17TH AVE
|
| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA306214 |
| SRA |
SRP067484 |
