Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration.

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Abstract
Closed circular Moloney murine leukemia virus (M-MuLV) DNA was prepared from recently infected cells and cloned in a .lambda. vector. Four classes of cloned M-MuLV inserts were found: class 1, full length 8.8-kilobase (kb) inserts with 2 tandem long terminal repeats (LTR) of 600 base pairs [bp]; class 2, 8.2-kb inserts with a single copy of a LTR; class 3, M-MuLV DNA inserts with various portions deleted; and class 4, an 8.8-kb insert with an internal sequence inversion. Determination of nucleotide sequence at the junction between the 2 LTR from a class 1 insert suggested that circularization occurred by blunt-end ligation of an 8.8-kb linear DNA. The class 4 molecule had an inversion that was flanked by inverted LTR, each of which had lost 2 terminal bp at the inversion end points. Also, 4 bp that were present only once in standard M-MuLV DNA were duplicated at either end of the inversion. This molecule was interpreted as resulting from an integrative inversion in which M-MuLV DNA integrated into itself. Its analysis thus provided explicit information concerning the mechanism by which retrovirus DNA integrates into host cell DNA. Models of retrovirus integration based on bacterial DNA transposition mechanisms are proposed.