Three cardiovirus Leader proteins equivalently inhibit four different nucleocytoplasmic trafficking pathways

Journal Article · Thu Oct 15 04:00:00 EDT 2015 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2015.06.004· OSTI ID:22470191

Ciomperlik, Jessica J. ^[1]; Basta, Holly A. ^[2]

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1. Institute for Molecular Virology, and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI (United States)
2. Department of Biology, Rocky Mountain College, Billings, MT (United States)

Cardiovirus infections inhibit nucleocytoplasmic trafficking by Leader protein-induced phosphorylation of Phe/Gly-containing nucleoporins (Nups). Recombinant Leader from encephalomyocarditis virus, Theiler's murine encephalomyelitis virus and Saffold virus target the same subset of Nups, including Nup62 and Nup98, but not Nup50. Reporter cell lines with fluorescence mCherry markers for M9, RS and classical SV40 import pathways, as well as the Crm1-mediated export pathway, all responded to transfection with the full panel of Leader proteins, showing consequent cessation of path-specific active import/export. For this to happen, the Nups had to be presented in the context of intact nuclear pores and exposed to cytoplasmic extracts. The Leader phosphorylation cascade was not effective against recombinant Nup proteins. The findings support a model of Leader-dependent Nup phosphorylation with the purpose of disrupting Nup-transportin interactions. - Highlights: • Nup98, but not Nup50 becomes phosphorylated by cardiovirus Leader protein-dependent mechanisms. • At least four independent nucleocytoplasmic trafficking pathways are inhibited by this process. • Nups must be presented in a nuclear pore context for Leader-directed phosphorylation. • Leader, by itself, does not cause activation of cellular kinases.

• OSTI ID: 22470191
• Journal Information: Virology, Journal Name: Virology Vol. 484; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
FLUORESCENCE
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
VIRUSES