title: Viperin is induced following dengue virus type-2 (DENV-2) infection and has anti-viral actions requiring the C-terminal end of viperin.
abstract: The host protein viperin is an interferon stimulated gene (ISG) that is up-regulated during a number of viral infections. In this study we have shown that dengue virus type-2 (DENV-2) infection significantly induced viperin, co-incident with production of viral RNA and via a mechanism requiring retinoic acid-inducible gene I (RIG-I). Viperin did not inhibit DENV-2 entry but DENV-2 RNA and infectious virus release was inhibited in viperin expressing cells. Conversely, DENV-2 replicated to higher tires earlier in viperin shRNA expressing cells. The anti-DENV effect of viperin was mediated by residues within the C-terminal 17 amino acids of viperin and did not require the N-terminal residues, including the helix domain, leucine zipper and S-adenosylmethionine (SAM) motifs known to be involved in viperin intracellular membrane association. Viperin showed co-localisation with lipid droplet markers, and was co-localised and interacted with DENV-2 capsid (CA), NS3 and viral RNA. The ability of viperin to interact with DENV-2 NS3 was associated with its anti-viral activity, while co-localisation of viperin with lipid droplets was not. Thus, DENV-2 infection induces viperin which has anti-viral properties residing in the C-terminal region of the protein that act to restrict early DENV-2 RNA production/accumulation, potentially via interaction of viperin with DENV-2 NS3 and replication complexes. These anti-DENV-2 actions of viperin show both contrasts and similarities with other described anti-viral mechanisms of viperin action and highlight the diverse nature of this unique anti-viral host protein.
authors: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
authors: Karla J
authors: KJ
authors: Helbig
authors: Jillian M
authors: JM
authors: Carr
authors: Julie K
authors: JK
authors: Calvert
authors: Satiya
authors: S
authors: Wati
authors: Jennifer N
authors: JN
authors: Clarke
authors: Nicholas S
authors: NS
authors: Eyre
authors: Sumudu K
authors: SK
authors: Narayana
authors: Guillaume N
authors: GN
authors: Fiches
authors: Erin M
authors: EM
authors: McCartney
authors: Michael R
authors: MR
authors: Beard
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003715:Dengue / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D003716:Dengue Virus / Q000472:pathogenicity*; D006801:Humans; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells; D000090123:Viperin Protein
chemical_list: D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; C444427:RSAD2 protein, human; D000090123:Viperin Protein
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