Gastroenterology
Volume 119, Issue 6 , Pages 1649-1655 , December 2000

Two PKR inhibitor HCV proteins correlate with early but not sustained response to interferon

Received 19 January 2000 ,Accepted 26 July 2000.

References 

  1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359–362
  2. Alberti A, Chemello L, Benvegnù L. Natural history of hepatitis C. J Hepatol. 1999;31(suppl 1):17–24
  3. Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, et al. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic Non-A, Non-B Hepatitis Study Team. N Engl J Med. 1992;327:1899–1905
  4. Saito I, Miyamura T, Ohbayashi A, Harada H, Katayama T, Kikuchi S, et al. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1990;87:6547–6549
  5. Cavalletto L, Chemello L, Donada C, Casarin P, Belussi F, Bernardinello E, et al. The pattern of response to interferon alpha (α-IFN) predicts sustained response to a 6 month α-IFN and ribavirin retreatment for chronic hepatitis C. J Hepatol. 2000;33:128–134
  6. Yoshioka K, Kakumu S, Wakita T, Ishikawa T, Itoh Y, Takayanagi M, et al. Detection of hepatitis C virus by polymerase chain reaction and response to interferon alpha-therapy: relationship to genotypes of hepatitis C virus. Hepatology. 1992;16:293–299
  7. Dusheiko G, Schmilovitz-Weiss H, Brown D, McOmish F, Yap P, Sherlock S, et al. Hepatitis C genotypes: an investigation of type-specific differences in geographic origin and disease. Hepatology. 1994;19:13–18
  8. Chemello L, Cavalletto L, Bernardinello E, Guido M, Pontisso P, Alberti A. The effect of interferon alpha and ribavirin combination therapy in naive patients with chronic hepatitis C. J Hepatol. 1995;23:8–12
  9. Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, et al. Comparison of full-length sequence of interferon-sensitive and resistant hepatitis C virus 1b. Sensitivity to interferon is conferred by amino acid substitutions in the NS5A gene. J Clin Invest. 1995;96:224–230
  10. Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, et al. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med. 1996;334:77–81
  11. Niiyama G, Kimura T, Mitani K, Tsugeno H, Sengoku N, Kinoyama S, et al. Mutations in the non-structural 5A gene in chronic hepatitis C virus infected patients with interferon treatment (abstr). Hepatology. 1996;24:164A
  12. Chayama K, Tsubota A, Kabayashi M, Okamoto K, Hashimoto M, Miyano Y, et al. Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection. Hepatology. 1997;25:745–749
  13. Nakano I, Fukuda Y, Katano Y, Nakano S, Kumada T, Hayakawa T. Why is the interferon sensitivity determining region (ISDR) system useful in Japan?. J Hepatol. 1999;30:1014–1022
  14. Gale MJ, Korth MJ, Tang NM, Tan SL, Hopkins DA, Dever TE, et al. Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology. 1997;230:217–227
  15. Gale MJ, Blakely CM, Kwieciszewski B, Tan SL, Dossett M, Tang NM, et al. Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Mol Cell Biol. 1998;18:5208–5218
  16. Francois C, Duverlie G, Rebouillat D, Khorsi H, Castellan S, Blum HE, et al. Expression of hepatitis C virus proteins interferes with the antiviral action of interferon independently of PKR-mediated control of protein synthesis. J Virol. 2000;74:5587–5596
  17. Khorsi H, Castelain S, Wyseur A, Izopet J, Canva V, Rombout A, et al. Mutations of hepatitis C virus 1b NS5A 2209-2248 amino acid sequence do not predict the response to recombinant interferon-alpha therapy in French patients. J Hepatol. 1997;27:72–77
  18. Zeuzem S, Lee JH, Roth WK. Mutations in the nonstructural 5A gene of European hepatitis C virus isolates and response to interferon alpha. Hepatology. 1997;25:740–744
  19. Squadrito G, Leone F, Sartori M, Nalpas B, Berthelot P, Raimondo S, et al. Mutations in the nonstructural 5A region of hepatitis C virus and response of chronic hepatitis C to interferon alpha. Gastroenterology. 1997;113:567–572
  20. Squadrito G, Orlando ME, Cacciola I, Rumi MG, Artini M, Picciotto A, et al. Long-term response to interferon alpha is unrelated to “interferon sensitivity determining region” variability in patients with chronic hepatitis C virus-1b infection. J Hepatol. 1999;30:1023–1027
  21. Hofgartner WT, Polyak SJ, Sullivan DG, Carithers RL, Gretch DR. Mutations in the NS5A gene of hepatitis C virus in North American patients infected with HCV genotype 1a or 1b. J Med Virol. 1997;53:118–126
  22. Chung RT, Montho A, Dienstag JL, Kaplan LM. Mutations in the NS5A region do not predict interferon-responsiveness in American patients infected with genotype 1b hepatitis C virus. J Med Virol. 1999;58:353–358
  23. Taylor DR, Shi ST, Romano PR, Barber GN, Lai MMC. Inhibition of the interferon inducible protein kinase PKR by HCV E2 protein. Science. 1999;285:107–110
  24. Abid K, Quadri R, Negro F. Hepatitis C virus, the E2 envelope protein, and α-interferon resistance (abstr). Science. 2000;287:1555a
  25. Sarrazin C, Kornetzky I, Ruster B, Lee JH, Kronenberger B, Bruch K, et al. Mutations within the E2 and NS5A protein in patients infected with hepatitis C virus type 3a and correlation with treatment response. Hepatology. 2000;31:1360–1370
  26. Tisminetzky SG, Gerotto M, Pontisso P, Alberti A, Baralle FE. Genotypes of hepatitis C virus in Italian patients with chronic hepatitis C. Int Hepatol Commun. 1994;2:105–112
  27. Van de Peer Y, De Wachter R. TREECON for Windows: a software package for the construction and drawing of evolutionary trees for the Microsoft Windows environment. Comput Appl Biosci. 1994;10:569–570
  28. Polyak SJ, Paschal DM, McArdle S, Gale MJ, Maradpour D, Gretch DR. Characterization of the effects of hepatitis C virus nonstructural 5A protein expression in human cell lines and on interferon-sensitive virus replication. Hepatology. 1999;29:1262–1271
  29. Kurosaki M, Enomoto N, Murakami T, Sakuma I, Asahina Y, Yamamoto C, et al. Analysis of genotypes and amino acid residues 2209 to 2248 of the NS5A region of hepatitis C virus in relation to the response to interferon-beta therapy. Hepatology. 1997;25:750–753
  30. Sarrazin C, Berg T, Lee J-H, Teuber G, Dietrich CF, Roth WK, et al. Improved correlation between multiple mutations within the NS5A region and virological response in European patients chronically infected with hepatitis C virus type 1b undergoing combination therapy. J Hepatol. 1999;30:1004–1013
  31. Kato N, Hijikata M, Ootsuyama Y, Nakagawa M, Ohkoshi S, Sugimura T, et al. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci U S A. 1990;87:9524–9528

 Address requests for reprints to: Alfredo Alberti, Department of Clinical and Experimental Medicine, University of Padua, Via Giustiniani 2, Padua 35128, Italy. e-mail: labepvir@ux1.unipd.it; fax: (39) 49-821-1826.

☆☆ Supported by grant MURST 40% 1998 (Prot. 9806107117_009), Ricerca Finalizzata Regione Veneto, 1997.

PII: S0016-5085(00)18673-1

Gastroenterology
Volume 119, Issue 6 , Pages 1649-1655 , December 2000