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• W2344174841 abstract "Richard J. Samulski,* Arun Srivastava,+ Kenneth I. Berns, and Nicholas Muzyczka Department of Immunology and Medical Microbiology University of Florida College of Medicine Gainesville, Florida 32610 Summary We have isolated three types of pBR322-AAV re- combinant plasmids that contain deletions within the 145 bp AAV terminal repeats. When the plasmids were transfected into human cells, mutants that con- tained deletions within the left (type I) or right (type II) terminal repeat were viable. Of four mutants ex- amined that contained deletions in both termini (type Ill), only one was viable. All of the viable mutants produced AAV virions that contained wild-type AAV DNA. Furthermore, the viable type Ill deletion could be converted to a nonviable mutant by deleting all copies of an 11 bp sequence from its termini. We conclude that there is an efficient mechanism for correcting deletions within the AAV termini. A model that could account for these observations is also discussed. Introduction A number of insertion-like elements have been described that integrate into eucaryotic chromosomes. These include the Tyl element of yeast (Cameron et al., 1979; Farabaugh and Fink, 1980; Gafner and Philippsen, 1980) the copia- like elements of Drosophila (Finnegan et al., 1977; Levis et al., 1980; Dunsmuir et al., 1980) and retrovirus proviral sequences (Hughes et al., 1978; Sabran et al., 1979; Shimotohno et al., 1980). Adeno-associated virus (AAV), an unconditionally defective parvovirus, is similar to these insertion elements in several respects. At the structural level the linear AAV genome has both an inverted and a direct terminal repetition (Lusby et al., 1980) and the major AAV species shares with other insertion elements the terminal sequence 5’-TG...CA-3’ (Fife et al., 1977). In the absence of helper virus AAV can readily establish a latent infection in continuous tissue culture lines (Hoggan et al., 1972; Berns et al., 1975). Finally, analysis of the integrated AAV genome in latently infected cells indicates AAV inte- grates into random positions in the eucaryotic chromo- some (Berns et al., 1982) in a manner that leaves most of the AAV genome uninterrupted (Cheung et al., 1980). All these properties are exhibited by other insertion-like ele- ments. However, AAV is unusual in that its DNA can be efficiently rescued from latently infected cells when the host is superinfected with a helper virus (Hoggan et al.," @default.
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• W2344174841 date "1983-01-01" @default.
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• W2344174841 title "Recombinant Plasmids: Gene Correction within the Terminal Repeats of AAV" @default.
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