ausblenden:
Schlagwörter:
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Zusammenfassung:
Viperin is an interferon-induced protein with a
broad antiviral activity. This evolutionary conserved
protein contains a radical S-adenosyl-Lmethionine
(SAM) domain which has been shown
in vitro to hold a [4Fe-4S] cluster. We identified
tick-borne encephalitis virus (TBEV) as a novel
target for which human viperin inhibits production
of the viral genome RNA. Wt viperin was found to
require ER localization for full antiviral activity and
to interact with the cytosolic Fe/S protein assembly
factor CIAO1. Radiolabelling in vivo revealed incorporation
of 55Fe, indicative for the presence of an
Fe-S cluster. Mutation of the cysteine residues
ligating the Fe-S cluster in the central radical SAM
domain entirely abolished both antiviral activity
and incorporation of 55Fe. Mutants lacking the
extreme C-terminal W361 did not interact with
CIAO1, were not matured, and were antivirally
inactive. Moreover, intracellular removal of SAM
by ectopic expression of the bacteriophage T3
SAMase abolished antiviral activity. Collectively,
our data suggest that viperin requires CIAO1 for
[4Fe-4S] cluster assembly, and acts through an
enzymatic, Fe-S cluster- and SAM-dependent
mechanism to inhibit viral RNA synthesis
