Viruses, Vol. 9, Pages 259: LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends

Viruses, Vol. 9, Pages 259: LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends

Viruses doi: 10.3390/v9090259

Authors: Murilo Bueno Daniel Reyes Manuel Llano

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.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ybutBm
via IFTTT