Evidence map›Paper›PMID 18077728›Full record

ArticleJournal of virology2008

Identification of three interferon-inducible cellular enzymes that inhibit the replication of hepatitis C virus.

Dong Jiang, Haitao Guo, Chunxiao Xu, Jinhong Chang, Baohua Gu, Lijuan Wang, Timothy M Block, Ju-Tao Guo

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.

0numbers the graph read from it
0cells of the map it votes in
167citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

167 citing papers in PubMed, 300 citations in OpenAlex.

  1. Article
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  5. IFIT2-induced transcriptomic changes inFrontiers in cellular and infection microbiology · 2025
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  16. Differential Leukocyte Expression ofJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022
    Article
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  18. Review
  19. Review
  20. Article

107 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Dong JiangDrexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, 3805 Old Easton Road, Doylestown, PA 18902, USA.
Haitao Guo
Chunxiao Xu
Jinhong Chang
Baohua Gu
Lijuan Wang
Timothy M Block
Ju-Tao Guo
Drexel University · USFox Chase Cancer Center · US

Funding

Imino sugars for flavivirus infections of bioterrorU01AI061441 · NIAID · DREXEL UNIVERSITY · PI BLOCK, TIMOTHY M · 2005 to 2010
$7.8M
NIAID NIH HHS AI061441NIAID NIH HHS U01 AI061441
6 · The paper itself

Abstract

Hepatitis C virus (HCV) infection is a common cause of chronic hepatitis and is currently treated with alpha interferon (IFN-alpha)-based therapies. However, the underlying mechanism of IFN-alpha therapy remains to be elucidated. To identify the cellular proteins that mediate the antiviral effects of IFN-alpha, we created a HEK293-based cell culture system to inducibly express individual interferon-stimulated genes (ISGs) and determined their antiviral effects against HCV. By screening 29 ISGs that are induced in Huh7 cells by IFN-alpha and/or up-regulated in HCV-infected livers, we discovered that viperin, ISG20, and double-stranded RNA-dependent protein kinase (PKR) noncytolytically inhibited the replication of HCV replicons. Mechanistically, inhibition of HCV replication by ISG20 and PKR depends on their 3'-5' exonuclease and protein kinase activities, respectively. Moreover, our work, for the first time, provides strong evidence suggesting that viperin is a putative radical S-adenosyl-l-methionine (SAM) enzyme. In addition to demonstrating that the antiviral activity of viperin depends on its radical SAM domain, which contains conserved motifs to coordinate [4Fe-4S] cluster and cofactor SAM and is essential for its enzymatic activity, mutagenesis studies also revealed that viperin requires an aromatic amino acid residue at its C terminus for proper antiviral function. Furthermore, although the N-terminal 70 amino acid residues of viperin are not absolutely required, deletion of this region significantly compromises its antiviral activity against HCV. Our findings suggest that viperin represents a novel antiviral pathway that works together with other antiviral proteins, such as ISG20 and PKR, to mediate the IFN response against HCV infection.

Indexed as

Amino Acid SequenceAntiviral AgentsCell LineeIF-2 KinaseExonucleasesExoribonucleasesGene ExpressionGenome, ViralHepacivirusHumansInterferon-alphaMolecular Sequence DataOxidoreductases Acting on CH-CH Group DonorsProteinsRepliconRNA, ViralAntiviral AgentseIF-2 KinaseExonucleasesExoribonucleasesInterferon-alphaISG20 protein, humanOxidoreductases Acting on CH-CH Group DonorsProteinsRNA, ViralRSAD2 protein, humanS-AdenosylmethionineViperin Protein

Identifiers

PMID18077728
PMCPMC2258705
OpenAlexW2143671051

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.