Molecular biology of the adeno-associated viruses.

Abstract

The adeno-associated viruses (AAV) are small, defective, DNA viruses which require co-infection with an adenovirus for productive infection (Atchison et al., 1965; Hoggan et al., 1966; Smith et al., 1966; Parks et al., 1967). They have also been termed adenovirus-associated virus, adeno satellite virus, and adeno-associated virus satellite virus. AAV particles were first noted as smaller particles contaminating adenovirus preparations when the latter were observed in the electron microscope (Archetti and Bocciarelli, 1963, 1964, 1965; Brandon and McLean, 1962; Hoggan, 1965; Hull et al., 1965; Melnick et al., 1965). Although initially considered to be cellular debris, or precursors or breakdown products of adenovirus, AAV was subsequently shown to be a separate virus which was structurally, immunologically, and genetically distinct from adenovirus (Atchison et al., 1965; Hoggan et al., 1966; Smith et al., 1966; Parks et al., 1967). The defectiveness of AAV with the subsequent requirement of an adenovirus as a helper was also shown at that time by these groups. Initially four distinctive serotypes of AAV were identified, AAV 1–3 from humans and AAV 4 from monkeys (see Hoggan, 1970).Subsequently, similar small viruses have been found associated with bovine, avian, and canine adenoviruses (Luchsinger et al., 1970; Dutta and Pomeroy, 1967; Yates et al, 1972; Domoto and Yanagawa, 1969).