Characterization of a nuclear localization signal in the C-terminus of the adeno-associated virus Rep68/78 proteins

Journal Article · Fri Oct 01 04:00:00 EDT 2004 · Virology

DOI:https://doi.org/10.1016/j.virol.2004.06.034· OSTI ID:20634875

Cassell, Geoffrey D ^[1]; Weitzman, Matthew D ^[1]

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1. Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037 (United States)

Adeno-associated virus (AAV) replicates in the nucleus of infected cells, and therefore multiple nuclear import events are required for productive infection. We analyzed nuclear import of the viral Rep proteins and characterized a nuclear localization signal (NLS) in the C-terminus. We demonstrate that basic residues in this region constitute an NLS that is transferable and mediates interaction with the nuclear import receptor importin {alpha} in vitro. Mutant Rep proteins are predominantly cytoplasmic and are severely compromised for interactions with importin {alpha}, but retain their enzymatic functions in vitro. Interestingly, mutations of the NLS had significantly less effect on importin {alpha} interaction and replication in the context of Rep78 than when incorporated into the Rep68 protein. Together, our results demonstrate that a bipartite NLS exists in the shared part of Rep68 and Rep78, and suggest that an alternate entry mechanism may also contribute to nuclear localization of the Rep78 protein.

• OSTI ID: 20634875
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 327; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL NUCLEI
IN VITRO
MUTANTS
MUTATIONS
RECEPTORS
VIRUSES