Targeting viperin to the mitochondrion inhibits the thiolase activity of the trifunctional enzyme complex.

Understanding the mechanisms by which viruses evade host cell immune defenses is important for developing improved antiviral therapies. In an unusual twist, human cytomegalovirus co-opts the antiviral radical SAM enzyme viperin (virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible) to enhance viral infectivity. This process involves translocation of viperin to the mitochondrion, where it binds the β-subunit (HADHB) of the mitochondrial trifunctional enzyme complex that catalyzes thiolysis of β-ketoacyl-CoA esters as part of fatty acid β-oxidation.

Interactions between Viperin, Vesicle-Associated Membrane Protein A, and Hepatitis C Virus Protein NS5A Modulate Viperin Activity and NS5A Degradation.

The radical SAM enzyme, viperin, exerts a wide range of antiviral effects through both the synthesis of the antiviral nucleotide 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) and through its interactions with various cellular and viral proteins. Here we investigate the interaction of viperin with hepatitis C virus nonstructural protein 5A (NS5A) and the host sterol regulatory protein, vesicle-associated membrane protein A (VAP-33). NS5A and VAP-33 form part of the viral replication complex that is essential for replicating the RNA genome of the hepatitis C virus.

Viperin interacts with the kinase IRAK1 and the E3 ubiquitin ligase TRAF6, coupling innate immune signaling to antiviral ribonucleotide synthesis.

Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (viperin) is a radical SAM enzyme that plays a multifaceted role in the cellular antiviral response. Viperin has recently been shown to catalyze the SAM-dependent formation of 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), which inhibits some viral RNA polymerases. Viperin is also implicated in regulating Lys-63-linked polyubiquitination of interleukin-1 receptor-associated kinase-1 (IRAK1) by the E3 ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6) as part of the Toll-like receptor-7 and -9 (TLR7/9) innate immune signaling pathways.

Controllable formation of heterotrimetallic coordination compounds: systematically incorporating lanthanide and alkali metal ions into the manganese 12-metallacrown-4 framework.

The inclusion of Ln(III) ions into the 12-MC-4 framework generates the first heterotrimetallic complexes of this molecular class. The controllable and deliberate preparations of these compounds are demonstrated through 12 crystal structures of the Ln(III)M(I)(OAc)4[12-MCMn(III)(N)shi-4](H2O)4·6DMF complex, where OAc(-) is acetate, shi(3-) is salicylhydroximate, and DMF is N,N-dimethylformamide. Compounds 1-12 have M(I) as Na(I), and Ln(III) can be Pr(III) (1), Nd(III) (2), Sm(III) (3), Eu(III) (4), Gd(III) (5), Tb(III) (6), Dy(III) (7), Ho(III) (8), Er(III) (9), Tm(III) (10), Yb(III) (11), and Y(III) (12).