Use of Adeno-Associated Virus as a General Transduction Vector for Mammalian Cells

Abstract

Adeno-associated virus (AAV) is a human virus that can be propagated either as an integrated provirus or by lytic infection (Atchison et al. 1965; Hoggan et al. 1966, 1972). The ability to form a latent infection appears to be an integral part of the AAV life cycle. Except under special circumstances (Yacobson et al. 1987; Schlehofer et al. 1986; Yalkinoglu et al. 1988), AAV requires the presence of a helper virus to initiate a productive viral infection (Fig. 1). Members of either the herpes or adenovirus families can provide the necessary helper functions (Atchison et al. 1965; Melnick et al. 1965; Hoggan et al. 1966; Buller et al. 1981; McPherson et al. 1985) and vaccinia virus can provide at least partial helper function (Schlehofer et al. 1986). In the absence of a helper virus AAV produces no progeny virus, but instead integrates into a host chromosome (Hoggan et al. 1972; Berns et al. 1975; Handa et al. 1977; Cheung et al. 1980). With rare exceptions, AAV proviruses appear to be stable. However, if a cell line that is carrying an AAV provirus (Fig. 1) is subsequently superinfected with a helper virus, the AAV genome is excised and proceeds through a normal productive infection (Hoggan et al. 1972; Cheung et al. 1980). This ability to establish a latent infection which can later be rescued appears to be a mechanism for ensuring the survival of AAV in the absence of a helper virus. The unusual life cycle of AAV has led a number of parvovirus laboratories to explore the possibility of using AAV as a general mammalian transduction vector.