Ebola virus VP24 proteins inhibit the interaction of NPi-1 subfamily karyopherin α proteins with activated STAT1

St Patrick Reid, Charalampos Valmas, Osvaldo Martinez, Freddy Mauricio Sanchez, Christopher F. Basler

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

The Zaire ebolavirus protein VP24 was previously demonstrated to inhibit alpha/beta interferon (IFN-α/β)-and IFN-γ-induced nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1) and to inhibit IFN-α/β- and IFN-γ-induced gene expression. These properties correlated with the ability of VP24 to interact with the nuclear localization signal receptor for PY-STAT1, karyopherin α1. Here, VP24 is demonstrated to interact not only with overexpressed but also with endogenous karyopherin α1. Mutational analysis demonstrated that VP24 binds within the PY-STAT1 binding region located in the C terminus of karyopherin α1. In addition, VP24 was found to inhibit PY-STAT1 binding to both overexpressed and endogenous karyopherin α1. We assessed the binding of both PY-STAT1 and the VP24 proteins from Zaire, mouse-adapted Zaire, and Reston Ebola viruses for interaction with all six members of the human karyopherin α family. We found, in contrast to previous studies, that PY-STAT1 can interact not only with karyopherin α1 but also with karyopherins α5 and α6, which together comprise the NPI-1 subfamily of karyopherin αs. Similarly, all three VP24s bound and inhibited PY-STAT1 interaction with karyopherins α1, α5, and α6. Consistent with their ability to inhibit the karyopherin-PY-STAT1 interaction, Zaire, mouse-adapted Zaire, and Reston Ebola virus VP24s displayed similar capacities to inhibit IFN-β-induced gene expression in human and mouse cells. These findings suggest that VP24 inhibits interaction of PY-STAT1 with karyopherins α1, α5, or α6 by binding within the PY-STAT1 binding region of the karyopherins and that this function is conserved among the VP24 proteins of different Ebola virus species.

Original languageEnglish (US)
Pages (from-to)13469-13477
Number of pages9
JournalJournal of virology
Volume81
Issue number24
DOIs
StatePublished - Dec 1 2007

Fingerprint

karyopherins
Ebolavirus
Karyopherins
Zaire Ebola virus
Proteins
proteins
Democratic Republic of the Congo
Reston Ebola virus
Ebola virus VP24 protein
mice
STAT1 Transcription Factor
interferon-beta
Gene Expression
Nuclear Localization Signals
nuclear localization signals
gene expression
Interferon-beta

ASJC Scopus subject areas

  • Immunology

Cite this

Ebola virus VP24 proteins inhibit the interaction of NPi-1 subfamily karyopherin α proteins with activated STAT1. / Reid, St Patrick; Valmas, Charalampos; Martinez, Osvaldo; Sanchez, Freddy Mauricio; Basler, Christopher F.

In: Journal of virology, Vol. 81, No. 24, 01.12.2007, p. 13469-13477.

Research output: Contribution to journalArticle

Reid, St Patrick ; Valmas, Charalampos ; Martinez, Osvaldo ; Sanchez, Freddy Mauricio ; Basler, Christopher F. / Ebola virus VP24 proteins inhibit the interaction of NPi-1 subfamily karyopherin α proteins with activated STAT1. In: Journal of virology. 2007 ; Vol. 81, No. 24. pp. 13469-13477.
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