Viperin Is Induced following Dengue Virus Type-2 (DENV-2) Infection and Has Anti-viral Actions Requiring the C-terminal End of Viperin

被引:128
作者
Helbig, Karla J. [1 ]
Carr, Jillian M. [2 ]
Calvert, Julie K. [2 ]
Wati, Satiya [1 ]
Clarke, Jennifer N. [2 ]
Eyre, Nicholas S. [1 ]
Narayana, Sumudu K. [1 ]
Fiches, Guillaume N. [1 ]
McCartney, Erin M. [1 ]
Beard, Michael R. [1 ]
机构
[1] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia
[2] Flinders Univ S Australia, Sch Med, Adelaide, SA 5001, Australia
来源
PLOS NEGLECTED TROPICAL DISEASES | 2013年 / 7卷 / 04期
基金
澳大利亚国家健康与医学研究理事会;
关键词
AMPHIPATHIC ALPHA-HELIX; PROTEIN VIPERIN; HUMAN CYTOMEGALOVIRUS; REPLICATION; INTERFERON; EXPRESSION; IDENTIFICATION; MACROPHAGES; SITES; CELLS;
D O I
10.1371/journal.pntd.0002178
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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 antiviral host protein.
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