A novel mutant loxP containing part of long terminal repeat of HIV-1 in spacer region: presentation of possible target site for antiviral strategy using site-specific recombinase.

A site-specific recombinase Cre is responsible for the recombination at a 34 bp loxP site. This system has been investigated for the antiviral strategy to excise proviral DNA from retrovirus-infected cells. It was reported that loxP sites could be inserted into long terminal repeat (LTR) of retrovirus to delete proviral DNA. To apply this system to human immunodeficiency virus type 1 (HIV-1) without inserting any DNA, one 34 bp sequence was selected from LTR of recombinant HIV-1 clone, loxLTR-1, based on sequence similarity between LTR and loxP, and sequence arrangement of 8 bp middle part in 34 bp LTR segment. When the 8 bp spacer region of loxP was changed into the corresponding middle part of loxLTR-1, this variant loxP would allow Cre to specifically recombine between themselves but not with wild-type loxP in vitro. This study suggests that site-specific excision of proviral DNA of HIV-1 could be catalyzed by the least modified Cre recognizing the loxLTR-1 sites.