Although 80-90% of adults are seropositive for antibodies against the
human parvovirus adeno-associated virus (AAV), infection has not been
associated with either symptoms or disease. In cell culture, AAV infec
tion is not productive unless there is a coinfection with a helper vir
us, either adenovirus or any type of herpes virus; in the absence of a
helper virus coinfection the viral genome is integrated into the geno
me, usually at a specific site on chromosome 19q13.3-qter. The integra
ted genome can be activated and rescued by subsequent super infection
by a helper virus. The high frequency of site-specific integration by
AAV and the lack of associated disease have encouraged the use of AAV
as a vector for gene therapy. This review will focus on the molecular
mechanisms involved in the establishment of, and rescue from, the late
nt state and their relevance to use of AAV as a vector.