“…These findings include (i) our previous report that multiple uracils silenced transcription from both HIV-1 LTR and CMV promoters in a cell line ( Weil et al, 2013 ), (ii) uracils within the origin of replication in HSV-1 perturb the binding of HSV-1 origin binding protein ( Focher et al, 1992 ), (iii) U/A pairs disrupt AP-1 transcription factor DNA binding ( Rogstad et al, 2002 ), (iv) singly uracilated DNA disrupts RNase H splicing specificity during reverse transcription Klarmann, 2003 , (v) U/A pairs perturb maintenance of telomere length in B cells by disruption of sheltrin binding ( Vallabhaneni et al, 2015 ), and (vi) one or two U/A base pairs within the specific cleavage site of some restriction enzymes prevents DNA strand cleavage ( Roberts et al, 2015 ). In addition, the abasic site product of uracil excision is known to exert a large negative effect on transcription ( Luhnsdorf et al, 2014 ) as would any mutations in transcription factor recognition sequences arising from error prone repair of excised uracils ( Shah et al, 2015 ; Emiliani, 1998 ). Combined, these potential effects of U/A pairs could profoundly silence HIV gene expression.…”