ing transcription or replication. Little is known about what may influence the choice of a chromosomal DNA target site during infection. Factors which may impact this selection include chromatin structure, target DNA sequence, host cell proteins and virus-encoded proteins other than integrase.
Previous approaches to the question of what may govern target site selection in vivo have primarily relied on cloning integrated proviruses and sequencing the flanking cellular DNA. These techniques are inherently time-consuming and it is therefore impractical to analyze a large number of independent integration events. Nonetheless, such studies have shown that both avian and murine retroviruses are able to integrate into sites which do not display any obvious sequence similarity( ). Other studies have indicated that integration may be targeted to certain structural features of chromatin, such as those associated with active transcription(I0.l1) and/or displaying hypersensitivity to the enzyme DNase 1 (12213,. The results of these studies, however, may misrepresent the actual frequency and distribution of all possible target sites in the genome because integration into a subset of sites may confer a selective growth advantage to some infected cells prior to cloning.