Interactions of Human Cytomegalovirus Proteins with the Nuclear Transport Machinery
Accurate cellular localization is crucial for the effective function of most viral macromolecules and nuclear translocation is central to the function of herpesviral proteins that are involved in processes such as transcription and DNA replication. The pa
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Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nuclear Import and Export Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Protein Import and Export . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nuclear RNA Export . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Interaction of the Human Cytomegalovirus Protein pUL69 with the mRNA Export Factor UAP56. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RNA Export by pUL69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Interaction of the HCMV pUL84 with Importin-α Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . Unconventional Interactions with the Nuclear Transport Machinery: Novel Targets for Antiviral Strategies? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Accurate cellular localization is crucial for the effective function of most viral macromolecules and nuclear translocation is central to the function of herpesviral proteins that are involved in processes such as transcription and DNA replication. The passage of large molecules between the cytoplasm and nucleus, however, is restricted, and this restriction affords specific mechanisms that control nucleocytoplasmic exchange. In this review, we focus on two cytomegalovirusencoded proteins, pUL69 and pUL84, that are able to shuttle between the nucleus and the cytoplasm. Both viral proteins use unconventional interactions with components of the cellular transport machinery: pUL69 binds to the mRNA export factor UAP56, and this interaction is crucial for pUL69-mediated nuclear export of unspliced RNA; pUL84 docks to importin-α proteins via an unusually large protein domain that contains functional leucine-rich nuclear export signals, thus serving as a complex bidirectional transport domain. Selective interference with
T. Stamminger Institute for Clinical and Molecular Virology, University Hospital, University of Erlangen-Nürnberg, Schlossgarten 4, 91054, Erlangen, Germany [email protected]
T.E. Shenk and M.F. Stinski (eds.), Human Cytomegalovirus. Current Topics in Microbiology and Immunology 325. © Springer-Verlag Berlin Heidelberg 2008
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these unconventional interactions, which disturbs the intracellular trafficking of important viral regulatory proteins, may constitute a novel and attractive principle for antiviral therapy.
Introduction A defining feature of the eukaryotic cell is its division into nucleoplasm and cytoplasm
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