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Plugging the holes in hepatitis C virus antiviral therapy

August 4, 2009
106 (31) 12567-12568
Research Article
The 3-dimensional structure of a hepatitis C virus p7 ion channel by electron microscopy
Philipp Luik, Chee Chew [...] Nicole Zitzmann

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Acknowledgments.

Work on p7 in my laboratory is funded by the United Kingdom Medical Research Council (G0700124), the Wellcome Trust (082812), and the Royal Society (RG081138).

References

1
AJ Hay, AJ Wolstenholme, JJ Skehel, MH Smith, The molecular basis of the specific anti-influenza action of amantadine. EMBO J 4, 3021–3024 (1985).
2
P Luik, et al., The 3-dimensional structure of a hepatitis C virus p7 ion channel by electron microscopy. Proc Natl Acad Sci USA 106, 12712–12716 (2009).
3
JR Schnell, JJ Chou, Structure and mechanism of the M2 proton channel of influenza A virus. Nature 451, 591–595 (2008).
4
AL Stouffer, et al., Structural basis for the function and inhibition of an influenza virus proton channel. Nature 451, 596–599 (2008).
5
SD Griffin, et al., The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine. FEBS Lett 535, 34–38 (2003).
6
D Pavlovic, et al., The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives. Proc Natl Acad Sci USA 100, 6104–6108 (2003).
7
A Premkumar, L Wilson, GD Ewart, PW Gage, Cation-selective ion channels formed by p7 of hepatitis C virus are blocked by hexamethylene amiloride. FEBS Lett 557, 99–103 (2004).
8
CT Jones, CL Murray, DK Eastman, J Tassello, CM Rice, Hepatitis C virus p7 and NS2 proteins are essential for production of infectious virus. J Virol 81, 8374–8383 (2007).
9
E Steinmann, et al., Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions. PLoS Pathog 3, e103 (2007).
10
A Sakai, et al., The p7 polypeptide of hepatitis C virus is critical for infectivity and contains functionally important genotype-specific sequences. Proc Natl Acad Sci USA 100, 11646–11651 (2003).
11
S Griffin, et al., Genotype-dependent sensitivity of hepatitis C virus to inhibitors of the p7 ion channel. Hepatology 48, 1779–1790 (2008).
12
E Steinmann, et al., Antiviral effects of amantadine and iminosugar derivatives against hepatitis C virus. Hepatology 46, 330–338 (2007).
13
CF Chew, R Vijayan, J Chang, N Zitzmann, PC Biggin, Determination of pore-lining residues in the hepatitis C virus p7 protein. Biophys J 96, L10–L12 (2009).
14
SD Griffin, et al., A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. J Gen Virol 85, 451–461 (2004).
15
Z Meshkat, M Audsley, C Beyer, EJ Gowans, G Haqshenas, Reverse genetic analysis of a putative, influenza virus M2 HXXXW-like motif in the p7 protein of hepatitis C virus. J Viral Hepat 16, 187–194 (2009).
16
NA Ilyushina, NV Bovin, RG Webster, EA Govorkova, Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 70, 121–131 (2006).
17
P Deltenre, et al., Evaluation of amantadine in chronic hepatitis C: a meta-analysis. J Hepatol 41, 462–473 (2004).
18
M Maynard, et al., Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI). J Hepatol 44, 484–490 (2006).
19
U Mihm, et al., Amino acid variations in hepatitis C virus p7 and sensitivity to antiviral combination therapy with amantadine in chronic hepatitis C. Antivir Ther 11, 507–519 (2006).
20
J Chan, K O'Riordan, TE Wiley, Amantadine's viral kinetics in chronic hepatitis C infection. Dig Dis Sci 47, 438–442 (2002).

Information & Authors

Information

Published in

The cover image for PNAS Vol.106; No.31
Proceedings of the National Academy of Sciences
Vol. 106 | No. 31
August 4, 2009
PubMed: 19666619

Submission history

Published online: August 4, 2009
Published in issue: August 4, 2009

Acknowledgments

Work on p7 in my laboratory is funded by the United Kingdom Medical Research Council (G0700124), the Wellcome Trust (082812), and the Royal Society (RG081138).

Notes

See companion article on page 12712.

Authors

Affiliations

Stephen D. C. Griffin1 [email protected]
Institute of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Mount Preston Street, Leeds LS2 9JT, United Kingdom

Notes

Author contributions: S.D.C.G. wrote the paper.

Competing Interests

The author declares no conflict of interest.

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    Plugging the holes in hepatitis C virus antiviral therapy
    Proceedings of the National Academy of Sciences
    • Vol. 106
    • No. 31
    • pp. 12563-13143

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