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Viruses 2017, 9(9), 259; doi:10.3390/v9090259

LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends

Department of Biological Sciences, University of Texas at El Paso. El Paso, TX 79968, USA
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Received: 12 August 2017 / Revised: 8 September 2017 / Accepted: 12 September 2017 / Published: 15 September 2017
(This article belongs to the Special Issue Viruses and the DNA Damage Response)
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Abstract

Processing of unintegrated linear HIV-1 cDNA by the host DNA repair system results in its degradation and/or circularization. As a consequence, deficient viral cDNA integration generally leads to an increase in the levels of HIV-1 cDNA circles containing one or two long terminal repeats (LTRs). Intriguingly, impaired HIV-1 integration in LEDGF/p75-deficient cells does not result in a correspondent increase in viral cDNA circles. We postulate that increased degradation of unintegrated linear viral cDNA in cells lacking the lens epithelium-derived growth factor (LEDGF/p75) account for this inconsistency. To evaluate this hypothesis, we characterized the nucleotide sequence spanning 2-LTR junctions isolated from LEDGF/p75-deficient and control cells. LEDGF/p75 deficiency resulted in a significant increase in the frequency of 2-LTRs harboring large deletions. Of note, these deletions were dependent on the 3′ processing activity of integrase and were not originated by aberrant reverse transcription. Our findings suggest a novel role of LEDGF/p75 in protecting the unintegrated 3′ processed linear HIV-1 cDNA from exonucleolytic degradation. View Full-Text
Keywords: LEDGF/p75; HIV-1; 2-LTR circles; unintegrated HIV-1 cDNA LEDGF/p75; HIV-1; 2-LTR circles; unintegrated HIV-1 cDNA
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Bueno, M.T.D.; Reyes, D.; Llano, M. LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends. Viruses 2017, 9, 259.

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