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Viperin is induced following dengue virus type-2 (DENV-2) infection and has anti-viral actions requiring the C-terminal end of viperin
- Source :
- PLoS Neglected Tropical Diseases, Vol 7, Iss 4, p e2178 (2013), PLoS Neglected Tropical Diseases
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
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.<br />Author Summary Viperin is a virally induced host protein that has been previously shown to have antiviral activity against a variety of viruses. Here we have demonstrated that viperin is also anti-viral against the medically significant arbovirus, dengue virus. Viperin was able to inhibit dengue virus at the level of viral replication, and cell lines unable to produce normal levels of viperin grew the virus to higher titres. These anti-dengue effects of viperin were mediated by amino acid residues in its C-terminus, and did not require structural domains of the N-terminal region as has been previously shown by us and others for the related virus, hepatitis C virus. Viperin was also demonstrated to co-localise and interact with the dengue capsid protein on the surface of lipid droplets, as well as with the NS3 protein and viral RNA. Viperin's association with NS3 was further demonstrated to be involved in its anti-dengue activities. The anti-viral activities of viperin presented in this manuscript show both similarities and contrasts with other described anti-viral mechanisms for the protein and highlight the diverse nature of this unique anti-viral host protein.
- Subjects :
- Viral Diseases
viruses
fluorescence resonance energy transfer
Dengue virus
medicine.disease_cause
Dengue Fever
Small hairpin RNA
Dengue
lipid structure
Chlorocebus aethiops
reverse transcriptase-polymerase chain reaction
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
lcsh:Public aspects of medicine
030302 biochemistry & molecular biology
virus diseases
Innate Immunity
3. Good health
Infectious Diseases
Viperin
Medicine
Research Article
Neglected Tropical Diseases
Leucine zipper
Oxidoreductases Acting on CH-CH Group Donors
RNA virus
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
Blotting, Western
Biology
Microbiology
lipids
03 medical and health sciences
Tropical Medicine
Cell Line, Tumor
medicine
Animals
Humans
Vero Cells
030304 developmental biology
NS3
dengue virus
Interferon-stimulated gene
Public Health, Environmental and Occupational Health
Immunity
RNA
Proteins
lcsh:RA1-1270
Dengue Virus
biochemical phenomena, metabolism, and nutrition
Virology
RNA extraction
Viral replication
viral replication
Parasitology
Subjects
Details
- Language :
- English
- ISSN :
- 19352735 and 19352727
- Volume :
- 7
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....5d46f84e19429140d23dfe8be633550d