F
IPR026372

S-adenosylmethionine-dependent nucleotide dehydratase RSAD2

InterPro entry
Short nameRSAD2
Overlapping
homologous
superfamilies
 

Description

S-adenosylmethionine-dependent nucleotide dehydratase RSAD2, also known as viperin (Virus Inhibitory Protein, ER-associated, Iterferon-inducible) is a radical SAM enzyme found in human and other vertebrates. It is both induced by interferon and demonstrably active in blocking replication by several types of virus, apparently by modifying lipid chemistries in lipid droplets and membrane rafts
[5, 6, 7, 8]
.

Human viperin is involved in antiviral defense, playing a major role in the cell antiviral state induced by type I and type II interferon
[12]
. It catalyses the conversion of cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP) via a SAM-dependent radical mechanism
[cite:PUB00103620]
,
[10]
. The resulting ddhCTP acts as a chain terminator for the RNA-dependent RNA polymerases from multiple viruses and directly inhibits viral replication
[9]
. It displays antiviral effect against a wide range of DNA and RNA viruses, such as HIV-1 virus, hepatitis C virus, human cytomegalovirus, and alphaviruses, but not vesiculovirus
[1, 2, 3, 8, 4, 11]
.

References

1.Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus. Chin KC, Cresswell P. Proc. Natl. Acad. Sci. U.S.A. 98, 15125-30, (2001). View articlePMID: 11752458

2.Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector. Helbig KJ, Lau DT, Semendric L, Harley HA, Beard MR. Hepatology 42, 702-10, (2005). View articlePMID: 16108059

3.TLR3 ligation activates an antiviral response in human fetal astrocytes: a role for viperin/cig5. Rivieccio MA, Suh HS, Zhao Y, Zhao ML, Chin KC, Lee SC, Brosnan CF. J. Immunol. 177, 4735-41, (2006). PMID: 16982913

4.Influenza virus not cRAFTy enough to dodge viperin. Waheed AA, Freed EO. Cell Host Microbe 2, 71-2, (2007). PMID: 18005719

5.Best5: a novel interferon-inducible gene expressed during bone formation. Grewal TS, Genever PG, Brabbs AC, Birch M, Skerry TM. FASEB J. 14, 523-31, (2000). PMID: 10698968

6.vig-1, a new fish gene induced by the rhabdovirus glycoprotein, has a virus-induced homologue in humans and shares conserved motifs with the MoaA family. Boudinot P, Massin P, Blanco M, Riffault S, Benmansour A. J. Virol. 73, 1846-52, (1999). PMID: 9971762

7.Molecular cloning of the viperin gene and its promoter region from the mandarin fish Siniperca chuatsi. Sun BJ, Nie P. Vet. Immunol. Immunopathol. 101, 161-70, (2004). View articlePMID: 15350746

8.Identification and characterization of interferon-induced proteins that inhibit alphavirus replication. Zhang Y, Burke CW, Ryman KD, Klimstra WB. J. Virol. 81, 11246-55, (2007). View articlePMID: 17686841

9.A naturally occurring antiviral ribonucleotide encoded by the human genome. Gizzi AS, Grove TL, Arnold JJ, Jose J, Jangra RK, Garforth SJ, Du Q, Cahill SM, Dulyaninova NG, Love JD, Chandran K, Bresnick AR, Cameron CE, Almo SC. Nature 558, 610-614, (2018). PMID: 29925952

10.Viperin interacts with the kinase IRAK1 and the E3 ubiquitin ligase TRAF6, coupling innate immune signaling to antiviral ribonucleotide synthesis. Dumbrepatil AB, Ghosh S, Zegalia KA, Malec PA, Hoff JD, Kennedy RT, Marsh ENG. J Biol Chem 294, 6888-6898, (2019). PMID: 30872404

11.A Viperin Mutant Bearing the K358R Substitution Lost its Anti-ZIKA Virus Activity. Vanwalscappel B, Gadea G, Despres P. Int J Mol Sci 20, E1574, (2019). PMID: 30934824

12.Targeting UBE4A Revives Viperin Protein in Epithelium to Enhance Host Antiviral Defense. Yuan Y, Miao Y, Qian L, Zhang Y, Liu C, Liu J, Zuo Y, Feng Q, Guo T, Zhang L, Chen X, Jin L, Huang F, Zhang H, Zhang W, Li W, Xu G, Zheng H. Mol Cell 77, 734-747.e7, (2020). PMID: 31812350

GO terms

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.