
Adeno-associated virus (AAV) was discovered as a contaminant of purified adenovirus preparations. Although the small icosahedral particles (diameter 18–28 nm) were initially considered to be either precursors to the mature adenovirus particle or breakdown products of the virion, they were rapidly demonstrated to represent a distinct virus that was physically, chemically, and immunologically unrelated to adenovirus (Atchison et al., 1965; Hoggan et al., 1966; Parks et al., 1967a,b). AAV was found to be absolutely defective and dependent on coinfection with the adenovirus for a productive infection. With additional studies, the reciprocity of the relationship between the two viruses has become clearer. Adenovirus not only helps AAV replication in a coinfection, but also serves to efficiently rescue the AAV genome from an integrated state in the DNA of cells latently infected by AAV (Hoggan et al., 1972; Berns et al., 1975; Handa et al., 1977). On the other hand, AAV inhibits the replication of adenovirus in a lytic coinfection (Hoggan et al., 1966; Smith et al., 1966; Casto et al., 1967; Parks et al., 1968) and can also inhibit the oncogenicity of both adenovirus (Kirchstein, et al., 1968; Casto and Goodheart, 1972; Mayor et al., 1973) and adenovirus-transformed cells (Ostrove et al., 1981; de la Maza and Carter, 1981).
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