Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells

Erik C. Hansen, Monica Ransom, Jay R. Hesselberth, Nina N. Hosmane, Adam A. Capoferri, Katherine M. Bruner, Ross A. Pollack, Hao Zhang, Michael Bradley Drummond, Janet M Siliciano, Robert F Siliciano, James Stivers

Research output: Contribution to journalArticle

Abstract

We report that a major subpopulation of monocyte-derived macrophages (MDMs) contains high levels of dUTP, which is incorporated into HIV-1 DNA during reverse transcription (U/ A pairs), resulting in pre-integration restriction and post-integration mutagenesis. After entering the nucleus, uracilated viral DNA products are degraded by the uracil base excision repair (UBER) machinery with less than 1% of the uracilated DNA successfully integrating. Although uracilated proviral DNA showed few mutations, the viral genomic RNA was highly mutated, suggesting that errors occur during transcription. Viral DNA isolated from blood monocytes and alveolar macrophages (but not T cells) of drug-suppressed HIV-infected individuals also contained abundant uracils. The presence of viral uracils in short-lived monocytes suggests their recent infection through contact with virus producing cells in a tissue reservoir. These findings reveal new elements of a viral defense mechanism involving host UBER that may be relevant to the establishment and persistence of HIV-1 infection.

Original languageEnglish (US)
Article numbere18447
JournaleLife
Volume5
Issue numberSeptember
DOIs
StatePublished - Sep 20 2016

Fingerprint

Uracil
Myeloid Cells
HIV-1
DNA
Viral DNA
Transcription
Infection
DNA Repair
Monocytes
Repair
Mutagenesis
T-cells
Macrophages
Alveolar Macrophages
Viral RNA
Viruses
Reverse Transcription
HIV Infections
Machinery
Blood

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hansen, E. C., Ransom, M., Hesselberth, J. R., Hosmane, N. N., Capoferri, A. A., Bruner, K. M., ... Stivers, J. (2016). Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells. eLife, 5(September), [e18447]. https://doi.org/10.7554/eLife.18447

Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells. / Hansen, Erik C.; Ransom, Monica; Hesselberth, Jay R.; Hosmane, Nina N.; Capoferri, Adam A.; Bruner, Katherine M.; Pollack, Ross A.; Zhang, Hao; Drummond, Michael Bradley; Siliciano, Janet M; Siliciano, Robert F; Stivers, James.

In: eLife, Vol. 5, No. September, e18447, 20.09.2016.

Research output: Contribution to journalArticle

Hansen, EC, Ransom, M, Hesselberth, JR, Hosmane, NN, Capoferri, AA, Bruner, KM, Pollack, RA, Zhang, H, Drummond, MB, Siliciano, JM, Siliciano, RF & Stivers, J 2016, 'Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells', eLife, vol. 5, no. September, e18447. https://doi.org/10.7554/eLife.18447
Hansen EC, Ransom M, Hesselberth JR, Hosmane NN, Capoferri AA, Bruner KM et al. Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells. eLife. 2016 Sep 20;5(September). e18447. https://doi.org/10.7554/eLife.18447
Hansen, Erik C. ; Ransom, Monica ; Hesselberth, Jay R. ; Hosmane, Nina N. ; Capoferri, Adam A. ; Bruner, Katherine M. ; Pollack, Ross A. ; Zhang, Hao ; Drummond, Michael Bradley ; Siliciano, Janet M ; Siliciano, Robert F ; Stivers, James. / Diverse fates of uracilated HIV-1 DNA during infection of myeloid lineage cells. In: eLife. 2016 ; Vol. 5, No. September.
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