Herpes simplex virus type 1 variant a sequence generated by recombination and breakage of the a sequence in defined regions, including the one involved in recombination

Abstract

A herpes simplex virus type 1 clone, GN29, having exclusively the variant a sequence was isolated. This a sequence was composed of unique (U) and directly repeated (DR) elements DR1, Ub, (DR2)14, Ucd, Ubd, (DR2)5, DR4n2, and Uc and was assumed to be generated by recombination between sites in Ub and Uc. Unusual DNA fragments containing parts of the a sequence, present in the DNA preparations of GN29, were molecularly cloned. Almost all termini of the cloned unusual DNA fragments were situated in defined regions assumed to be recombinogenic: (i) a site in the inverted repeat of the L component, (ii) DR1, (iii) DR2, (iv) the DR4 stretch, and (v) the novel recombination stretch in the variant a sequence of GN29. The termini of unusual DNA fragments, possibly produced by strand breaks, can serve as free DNA ends to initiate recombination of the a sequence. These results support the model of double-strand-break repair for recombination of the a sequence. Sequence-specific enhancement of the recombination of the a sequence probably depends on the presence of recombinogenic elements apt to break, such as DR2 repeats and the DR4 stretch.