Publication Type Academic Article
Authors Musatov S, Roberts J, Pfaff D, Kaplitt M
Journal J Virol
Volume 76
Issue 24
Pagination 12792-802
Date Published 12/01/2002
ISSN 0022-538X
Keywords Dependovirus, Terminal Repeat Sequences, Virus Assembly, Virus Replication
Abstract A novel pathway of adeno-associated virus (AAV) replication marked by the assembly of circular monomer duplex intermediates (cAAV) has been recently discovered. In the present report we identify a single AD domain of the inverted terminal repeat as a minimal origin of cAAV replication. A small internal palindrome (BB'), necessary for optimal Rep-inverted terminal repeat interaction, does not contribute to the efficiency of cAAV replication, while the terminal resolution site is an essential cis-acting element. Furthermore, recombinant cAAV vectors that encompass only the AD domain replicate exclusively in a circular form and no detectable linear duplex replicative intermediates are generated, suggesting that both pathways of AAV replication are independent and can be separated. In addition, we show that cAAVs are efficient templates for encapsidation of single-stranded DNA genomes, an observation that assigns a biological role for these novel replication species. Together, these findings shed new light on the current model of AAV replication and packaging.
DOI 10.1128/jvi.76.24.12792-12802.2002
PubMed ID 12438604
PubMed Central ID PMC136660
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