Biology Reference
In-Depth Information
Interactions of Human Cytomegalovirus
Proteins with the Nuclear Transport Machinery
T. Stamminger
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
Nuclear Import and Export Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Protein Import and Export . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Nuclear RNA Export . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Interaction of the Human Cytomegalovirus Protein pUL69 with the mRNA
Export Factor UAP56. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
RNA Export by pUL69 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
Interaction of the HCMV pUL84 with Importin-α Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Unconventional Interactions with the Nuclear Transport Machinery: Novel Targets
for Antiviral Strategies? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
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 cytomegalovirus-
encoded proteins, pUL69 and pUL84, that are able to shuttle between the nucleus
and the cytoplasm. Both viral proteins use unconventional interactions with com-
ponents 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
thomas.stamminger@viro.med.uni-erlangen.de
