Rescue and Replication of the Adeno-Associated Virus 2 Genome in Mortal and Immortal Human Cells

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Abstract
Productive infection of the adeno-associated virus (AAV) as well as rescue of the AAV genome from a recombinant plasmid and its subsequent replication in established cell lines are dependent upon coinfection with adenovirus. A comparative study of AAV infection and rescue/replication was carried out in mortal and immortal human cells. AAV DNA replication as well as assembly and release of the progeny virions were significantly delayed in normal diploid cells, which have a limited replicative potential, compared with polyploid cells, which have an unlimited proliferative potential. Rescue of the AAV genome from a recombinant plasmid and its subsequent replication were similarly delayed in mortal cells. The delay in AAV rescue/replication appeared to be unrelated to the adenovirus-encoded functions. The putative host-cell component required for AAV replication may be suboptimally induced in normal human diploid cells, which offer a useful model system for a natural AAV infection.