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Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons

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Title:Importin α1 is required for nuclear import of herpes simplex virus proteins and capsid assembly in fibroblasts and neurons
Creators Name:Döhner, K. and Ramos-Nascimento, A. and Bialy, D. and Anderson, F. and Hickford-Martinez, A. and Rother, F. and Koithan, T. and Rudolph, K. and Buch, A. and Prank, U. and Binz, A. and Hügel, S. and Lebbink, R.J. and Hoeben, R.C. and Hartmann, E. and Bader, M. and Bauerfeind, R. and Sodeik, B.
Abstract:Herpesviruses are large DNA viruses which depend on many nuclear functions, and therefore on host transport factors to ensure specific nuclear import of viral and host components. While some import cargoes bind directly to certain transport factors, most recruit importin β1 via importin α. We identified importin α1 in a small targeted siRNA screen to be important for herpes simplex virus (HSV-1) gene expression. Production of infectious virions was delayed in the absence of importin α1, but not in cells lacking importin α3 or importin α4. While nuclear targeting of the incoming capsids, of the HSV-1 transcription activator VP16, and of the viral genomes were not affected, the nuclear import of the HSV-1 proteins ICP4 and ICP0, required for efficient viral transcription, and of ICP8 and pUL42, necessary for DNA replication, were reduced. Furthermore, quantitative electron microscopy showed that fibroblasts lacking importin α1 contained overall fewer nuclear capsids, but an increased proportion of mature nuclear capsids indicating that capsid formation and capsid egress into the cytoplasm were impaired. In neurons, importin α1 was also not required for nuclear targeting of incoming capsids, but for nuclear import of ICP4 and for the formation of nuclear capsid assembly compartments. Our data suggest that importin α1 is specifically required for the nuclear localization of several important HSV1 proteins, capsid assembly, and capsid egress into the cytoplasm, and may become rate limiting in situ upon infection at low multiplicity or in terminally differentiated cells such as neurons.
Keywords:alpha Karyopherins, Capsid, Capsid Proteins, Cell Line, Cell Nucleus, Cell Nucleus Active Transport, Fibroblasts, HEK293 Cells, HeLa Cells, Human Herpesvirus 1, Inbred C57BL Mice, Knockout Mice, Neurons, Virus Assembly, Animals, Cricetinae, Mice
Source:PLoS Pathogens
Publisher:Public Library of Science
Page Range:e1006823
Date:5 January 2018
Official Publication:https://doi.org/10.1371/journal.ppat.1006823
PubMed:View item in PubMed

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