Next generation sequencing of the hepatitis C virus NS5B gene reveals potential novel S282 drug resistance mutations

Virology

Volumn 477, Issue , 2015, Pages 1-9

  Ji, Hezhao ^a   Kozak, Robert A ^b   Biondi, Mia J ^c   Pilon, Richard ^a   Vallee, Dominic ^a   Liang, Ben Binhua ^a   La, David ^a   Kim, John ^a   Van Domselaar, Gary ^a   Leonard, Lynne ^d   Sandstrom, Paul ^a   Brooks, James ^a  

^a PUBLIC HEALTH AGENCY OF CANADA   (Canada)

^b UNIVERSITY OF GUELPH   (Canada)

^c UNIVERSITY OF WESTERN ONTARIO   (Canada)

^d UNIVERSITY OF OTTAWA   (Canada)

Author keywords

Drug resistance mutation; HCV; In silico molecular modeling; NS5B; Pyrosequencing

Indexed keywords

INTERFERON; NONSTRUCTURAL PROTEIN 5B; RIBAVIRIN; SOFOSBUVIR; ANTIVIRUS AGENT; MUTANT PROTEIN; NS-5 PROTEIN, HEPATITIS C VIRUS; VIRAL PROTEIN;

ADULT; AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; ARTICLE; CODON; CONSENSUS SEQUENCE; CONTROLLED STUDY; FEMALE; GENE MUTATION; GENETIC POLYMORPHISM; HEPATITIS C VIRUS; HEPATITIS C VIRUS SUBTYPE 1A; HEPATITIS C VIRUS SUBTYPE 1B; HEPATITIS C VIRUS SUBTYPE 2A; HEPATITIS C VIRUS SUBTYPE 2B; HEPATITIS C VIRUS SUBTYPE 3A; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; INTRAVENOUS DRUG ABUSE; MAJOR CLINICAL STUDY; MALE; MIXED INFECTION; MOLECULAR MODEL; NEXT GENERATION SEQUENCING; NONHUMAN; NS5B GENE; PYROSEQUENCING; CHRONIC HEPATITIS C; COHORT ANALYSIS; COMPLICATION; DRUG EFFECTS; GENETICS; HEPACIVIRUS; HIGH THROUGHPUT SEQUENCING; ISOLATION AND PURIFICATION; MIDDLE AGED; MISSENSE MUTATION; PROCEDURES; SUBSTANCE ABUSE; TREATMENT OUTCOME; VIROLOGY;

HEPATITIS C VIRUS;

ADULT; ANTIVIRAL AGENTS; COHORT STUDIES; DRUG RESISTANCE, VIRAL; FEMALE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; MALE; MIDDLE AGED; MUTANT PROTEINS; MUTATION, MISSENSE; SUBSTANCE ABUSE, INTRAVENOUS; TREATMENT OUTCOME; VIRAL NONSTRUCTURAL PROTEINS;

EID: 84921294287     PISSN: 00426822     EISSN: 10960341     Source Type: Journal    
DOI: 10.1016/j.virol.2014.12.037     Document Type: Article

References (61)

1. Afdhal N., Reddy K.R., Nelson D.R., Lawitz E., Gordon S.C., Schiff E., Nahass R., Ghalib R., Gitlin N., Herring R., Lalezari J., Younes Z.H., Pockros P.J., Di Bisceglie A.M., Arora S., Subramanian G.M., Zhu Y., Dvory-Sobol H., Yang J.C., Pang P.S., Symonds W.T., McHutchison J.G., Muir A.J., Sulkowski M., Kwo P. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N. Engl. J. Med. 2014, 370:1483-1493.
2. Afdhal N., Zeuzem S., Kwo P., Chojkier M., Gitlin N., Puoti M., Romero-Gomez M., Zarski J.P., Agarwal K., Buggisch P., Foster G.R., Brau N., Buti M., Jacobson I.M., Subramanian G.M., Ding X., Mo H., Yang J.C., Pang P.S., Symonds W.T., McHutchison J.G., Muir A.J., Mangia A., Marcellin P. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N. Engl. J. Med 2014, 370:1889-1898.
3. Ali S., Leveque V., Le P.S., Ma H., Philipp F., Inocencio N., Smith M., Alker A., Kang H., Najera I., Klumpp K., Symons J., Cammack N., Jiang W.R. Selected replicon variants with low-level in vitro resistance to the hepatitis C virus NS5B polymerase inhibitor PSI-6130 lack cross-resistance with R1479. Antimicrob. Agents Chemother. 2008, 52:4356-4369.
4. Aloia A.L., Locarnini S., Beard M.R. Antiviral resistance and direct-acting antiviral agents for HCV. Antivir. Ther. 2012, 17:1147-1162.
5. Alves R., Queiroz A.T., Pessoa M.G., da Silva E.F., Mazo D.F., Carrilho F.J., Carvalho-Filho R.J., de Carvalho I.M. The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank. J. Viral Hepat. 2013, 20:414-421.
6. Applegate T.L., Gaudieri S., Plauzolles A., Chopra A., Grebely J., Lucas M., Hellard M., Luciani F., Dore G.J., Matthews G.V. Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C. Antivir. Ther. 2014, http://dx.doi.org/10.3851/IMP2821. [Epub ahead of print].
7. Asahina Y., Izumi N., Enomoto N., Uchihara M., Kurosaki M., Onuki Y., Nishimura Y., Ueda K., Tsuchiya K., Nakanishi H., Kitamura T., Miyake S. Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C. J. Hepatol. 2005, 43:623-629.
8. Bartels D.J., Sullivan J.C., Zhang E.Z., Tigges A.M., Dorrian J.L., De M.S., Takemoto D., Dondero E., Kwong A.D., Picchio G., Kieffer T.L. Hepatitis C virus variants with decreased sensitivity to direct-acting antivirals (DAAs) were rarely observed in DAA-naive patients prior to treatment. J. Virol. 2013, 87:1544-1553.
9. Boom R., Sol C.J., Salimans M.M., Jansen C.L., Wertheim-Van Dillen P.M., van der Noordaa J. Rapid and simple method for purification of nucleic acids. J. Clin. Microbiol. 1990, 28:495-503.
10. Donaldson E.F., Harrington P.R., O'Rear J.J., Naeger L.K. Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for Sofosbuvir. Hepatology 2015, 61:56-65.
11. Franco S., Casadella M., Noguera-Julian M., Clotet B., Tural C., Paredes R., Martinez M.A. No detection of the NS5B S282T mutation in treatment-naive genotype 1 HCV/HIV-1 coinfected patients using deep sequencing. J. Clin. Virol. 2013, 58:726-729.
12. Gane E.J., Stedman C.A., Hyland R.H., Ding X., Svarovskaia E., Symonds W.T., Hindes R.G., Berrey M.M. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N. Engl. J. Med. 2013, 368:34-44.
13. Gotte M. Resistance to nucleotide analogue inhibitors of hepatitis C virus NS5B: mechanisms and clinical relevance. Curr. Opin. Virol. 2014, 8:104-108.
14. Grebely J., Raffa J.D., Lai C., Krajden M., Kerr T., Fischer B., Tyndall M.W. Low uptake of treatment for hepatitis C virus infection in a large community-based study of inner city residents. J. Viral Hepat. 2009, 16:352-358.
15. Hall T.A. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp. Ser. 1999, 41:95-98.
16. Hamano K., Sakamoto N., Enomoto N., Izumi N., Asahina Y., Kurosaki M., Ueda E., Tanabe Y., Maekawa S., Itakura J., Watanabe H., Kakinuma S., Watanabe M. Mutations in the NS5B region of the hepatitis C virus genome correlate with clinical outcomes of interferon-alpha plus ribavirin combination therapy. J. Gastroenterol. Hepatol. 2005, 20:1401-1409.
17. Howe A.Y., Cheng H., Johann S., Mullen S., Chunduru S.K., Young D.C., Bard J., Chopra R., Krishnamurthy G., Mansour T., O'Connell J. Molecular mechanism of hepatitis C virus replicon variants with reduced susceptibility to a benzofuran inhibitor, HCV-796. Antimicrob. Agents Chemother. 2008, 52:3327-3338.
18. Jacobson I.M., Gordon S.C., Kowdley K.V., Yoshida E.M., Rodriguez-Torres M., Sulkowski M.S., Shiffman M.L., Lawitz E., Everson G., Bennett M., Schiff E., Al-Assi M.T., Subramanian G.M., An D., Lin M., McNally J., Brainard D., Symonds W.T., McHutchison J.G., Patel K., Feld J., Pianko S., Nelson D.R. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N. Engl. J. Med. 2013, 368:1867-1877.
19. Jaspe R.C., Sulbaran Y.F., Sulbaran M.Z., Loureiro C.L., Rangel H.R., Pujol F.H. Prevalence of amino acid mutations in hepatitis C virus core and NS5B regions among Venezuelan viral isolates and comparison with worldwide isolates. Virol. J. 2012, 9:214.
20. Ji H., Li Y., Liang B., Pilon R., MacPherson P., Bergeron M., Kim J., Graham M., Van D.G., Sandstrom P., Brooks J. Pyrosequencing dried blood spots reveals differences in HIV drug resistance between treatment naive and experienced patients. PLoS One 2013, 8:e56170.
21. Ji H., Liang B., Li Y., Van D.G., Graham M., Tyler S., Merks H., Sandstrom P., Brooks J. Low abundance drug resistance variants in transmitted HIV drug resistance surveillance specimens identified using tagged pooled pyrosequencing. J. Virol. Methods 2013, 187:314-320.
22. Ji H., Masse N., Tyler S., Liang B., Li Y., Merks H., Graham M., Sandstrom P., Brooks J. HIV drug resistance surveillance using pooled pyrosequencing. PLoS One 2010, 5:e9263.
23. Karam P., Powdrill M.H., Liu H.W., Vasquez C., Mah W., Bernatchez J., Gotte M., Cosa G. Dynamics of hepatitis C virus (HCV) RNA-dependent RNA polymerase NS5B in complex with RNA. J. Biol. Chem. 2014, 289:14399-14411.
24. Kowdley K.V., Lawitz E., Crespo I., Hassanein T., Davis M.N., DeMicco M., Bernstein D.E., Afdhal N., Vierling J.M., Gordon S.C., Anderson J.K., Hyland R.H., Dvory-Sobol H., An D., Hindes R.G., Albanis E., Symonds W.T., Berrey M.M., Nelson D.R., Jacobson I.M. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial. Lancet 2013, 381:2100-2107.
25. Kuntzen T., Timm J., Berical A., Lennon N., Berlin A.M., Young S.K., Lee B., Heckerman D., Carlson J., Reyor L.L., Kleyman M., McMahon C.M., Birch C., Schulze Zur W.J., Ledlie T., Koehrsen M., Kodira C., Roberts A.D., Lauer G.M., Rosen H.R., Bihl F., Cerny A., Spengler U., Liu Z., Kim A.Y., Xing Y., Schneidewind A., Madey M.A., Fleckenstein J.F., Park V.M., Galagan J.E., Nusbaum C., Walker B.D., Lake-Bakaar G.V., Daar E.S., Jacobson I.M., Gomperts E.D., Edlin B.R., Donfield S.M., Chung R.T., Talal A.H., Marion T., Birren B.W., Henn M.R., Allen T.M. Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naive patients. Hepatology 2008, 48:1769-1778.
26. Lam A.M., Espiritu C., Bansal S., Micolochick Steuer H.M., Niu C., Zennou V., Keilman M., Zhu Y., Lan S., Otto M.J., Furman P.A. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob. Agents Chemother. 2012, 56:3359-3368.
27. Lam A.M., Espiritu C., Murakami E., Zennou V., Bansal S., Micolochick Steuer H.M., Niu C., Keilman M., Bao H., Bourne N., Veselenak R.L., Reddy P.G., Chang W., Du J., Nagarathnam D., Sofia M.J., Otto M.J., Furman P.A. Inhibition of hepatitis C virus replicon RNA synthesis by PSI-352938, a cyclic phosphate prodrug of beta-D-2'-deoxy-2'-alpha-fluoro-2'-beta-C-methylguanosine. Antimicrob. Agents Chemother. 2011, 55:2566-2575.
28. Lawitz E., Lalezari J.P., Hassanein T., Kowdley K.V., Poordad F.F., Sheikh A.M., Afdhal N.H., Bernstein D.E., Dejesus E., Freilich B., Nelson D.R., Dieterich D.T., Jacobson I.M., Jensen D., Abrams G.A., Darling J.M., Rodriguez-Torres M., Reddy K.R., Sulkowski M.S., Bzowej N.H., Hyland R.H., Mo H., Lin M., Mader M., Hindes R., Albanis E., Symonds W.T., Berrey M.M., Muir A. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect. Dis. 2013, 13:401-408.
29. Lawitz E., Mangia A., Wyles D., Rodriguez-Torres M., Hassanein T., Gordon S.C., Schultz M., Davis M.N., Kayali Z., Reddy K.R., Jacobson I.M., Kowdley K.V., Nyberg L., Subramanian G.M., Hyland R.H., Arterburn S., Jiang D., McNally J., Brainard D., Symonds W.T., McHutchison J.G., Sheikh A.M., Younossi Z., Gane E.J. Sofosbuvir for previously untreated chronic hepatitis C infection. N. Engl. J. Med. 2013, 368:1878-1887.
30. Le Pogam S., Seshaadri A., Ewing A., Kang H., Kosaka A., Yan J.M., Berrey M., Symonds B., De La Rosa A., Cammack N., Najera I. RG7128 alone or in combination with pegylated interferon-alpha2a and ribavirin prevents hepatitis C virus (HCV) Replication and selection of resistant variants in HCV-infected patients. J. Infect. Dis. 2010, 202:1510-1519.
31. Love R.A., Parge H.E., Yu X., Hickey M.J., Diehl W., Gao J., Wriggers H., Ekker A., Wang L., Thomson J.A., Dragovich P.S., Fuhrman S.A. Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme. J. Virol. 2003, 77:7575-7581.
32. Ludmerer S.W., Graham D.J., Boots E., Murray E.M., Simcoe A., Markel E.J., Grobler J.A., Flores O.A., Olsen D.B., Hazuda D.J., LaFemina R.L. Replication fitness and NS5B drug sensitivity of diverse hepatitis C virus isolates characterized by using a transient replication assay. Antimicrob. Agents Chemother. 2005, 49:2059-2069.
33. Maimone S., Tripodi G., Musolino C., Cacciola I., Pollicino T., Raimondo G. Lack of the NS5B S282T mutation in HCV isolates from liver tissue of naive patients with HCV genotype-1b infection. Antivir. Ther. 2014, http://dx.doi.org/10.3851/IMP2844. [Epub ahead of print].
34. Margeridon-Thermet S., Le P.S., Li L., Liu T.F., Shulman N., Shafer R.W., Najera I. Similar prevalence of low-abundance drug-resistant variants in treatment-naive patients with genotype 1a and 1b hepatitis C virus infections as determined by ultradeep pyrosequencing. PLoS One 2014, 9:e105569.
35. Mayhoub A.S. Hepatitis C RNA-dependent RNA polymerase inhibitors: a review of structure-activity and resistance relationships; different scaffolds and mutations. Bioorg. Med. Chem. 2012, 20:3150-3161.
36. McCown M.F., Rajyaguru S., Le P.S., Ali S., Jiang W.R., Kang H., Symons J., Cammack N., Najera I. The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors. Antimicrob. Agents Chemother. 2008, 52:1604-1612.
37. Mosley R.T., Edwards T.E., Murakami E., Lam A.M., Grice R.L., Du J., Sofia M.J., Furman P.A., Otto M.J. Structure of hepatitis C virus polymerase in complex with primer-template RNA. J. Virol. 2012, 86:6503-6511.
38. Myers R.P., Ramji A., Bilodeau M., Wong S., Feld J.J. An update on the management of hepatitis C: consensus guidelines from the Canadian Association for the Study of the Liver. Can. J. Gastroenterol. 2012, 26:359-375.
39. Neumann A.U., Lam N.P., Dahari H., Gretch D.R., Wiley T.E., Layden T.J., Perelson A.S. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998, 282:103-107.
40. O'Farrell D., Trowbridge R., Rowlands D., Jager J. Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): structural evidence for nucleotide import and de-novo initiation. J. Mol. Biol. 2003, 326:1025-1035.
41. Osinusi A., Kohli A., Marti M.M., Nelson A., Zhang X., Meissner E.G., Silk R., Townsend K., Pang P.S., Subramanian G.M., McHutchison J.G., Fauci A.S., Masur H., Kottilil S. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study. Ann. Intern. Med. 2014, 161:634-638.
42. Palanisamy N., Danielsson A., Kokkula C., Yin H., Bondeson K., Wesslen L., Duberg A.S., Lennerstrand J. Implications of baseline polymorphisms for potential resistance to NS3 protease inhibitors in Hepatitis C virus genotypes 1a, 2b and 3a. Antivir. Res. 2013, 99:12-17.
43. Pickett B.E., Striker R., Lefkowitz E.J. Evidence for separation of HCV subtype 1a into two distinct clades. J. Viral Hepat. 2011, 18:608-618.
44. Pilon R., Leonard L., Kim J., Vallee D., De R.E., Jolly A.M., Wylie J., Pelude L., Sandstrom P. Transmission patterns of HIV and hepatitis C virus among networks of people who inject drugs. PLoS One 2011, 6:e22245.
45. Poordad F., Hezode C., Trinh R., Kowdley K.V., Zeuzem S., Agarwal K., Shiffman M.L., Wedemeyer H., Berg T., Yoshida E.M., Forns X., Lovell S.S., Silva-Tillmann B.D., Collins C.A., Campbell A.L., Podsadecki T., Bernstein B. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N. Engl. J. Med 2014, 370:1973-1982.
46. Powdrill M.H., Tchesnokov E.P., Kozak R.A., Russell R.S., Martin R., Svarovskaia E.S., Mo H., Kouyos R.D., Gotte M. Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance. Proc. Natl. Acad. Sci.USA 2011, 108:20509-20513.
47. Ribeiro R.M., Li H., Wang S., Stoddard M.B., Learn G.H., Korber B.T., Bhattacharya T., Guedj J., Parrish E.H., Hahn B.H., Shaw G.M., Perelson A.S. Quantifying the diversification of hepatitis C virus (HCV) during primary infection: estimates of the in vivo mutation rate. PLoS Pathog. 2012, 8:e1002881.
48. Rodriguez-Torres M., Lawitz E., Kowdley K.V., Nelson D.R., Dejesus E., McHutchison J.G., Cornpropst M.T., Mader M., Albanis E., Jiang D., Hebner C.M., Symonds W.T., Berrey M.M., Lalezari J. Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naive patients with HCV genotype 1: a randomized, 28-day, dose-ranging trial. J. Hepatol. 2013, 58:663-668.
49. Rong L., Dahari H., Ribeiro R.M., Perelson A.S. Rapid emergence of protease inhibitor resistance in hepatitis C virus. Sci. Transl. Med. 2010, 2:30ra32.
50. Roy A., Kucukural A., Zhang Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat. Protoc. 2010, 5:725-738.
51. Roy A., Xu D., Poisson J., Zhang Y. A protocol for computer-based protein structure and function prediction. J. Vis. Exp. (57) 2011, e3259.
52. Shah H.A., Heathcote J., Feld J.J. A Canadian screening program for hepatitis C: is now the time?. Can. Med. Assoc. J. 2013, 185:1325-1328.
53. Svarovskaia E.S., Dvory-Sobol H., Parkin N., Hebner C., Gontcharova V., Martin R., Ouyang W., Han B., Xu S., Ku K., Chiu S., Gane E., Jacobson I.M., Nelson D.R., Lawitz E., Wyles D.L., Bekele N., Brainard D., Symonds W.T., McHutchison J.G., Miller M.D., Mo H. Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials. Clin. Infect. Dis. 2014, 59:1666-1674.
54. Svarovskaia E.S., Martin R., McHutchison J.G., Miller M.D., Mo H. Abundant drug-resistant NS3 mutants detected by deep sequencing in hepatitis C virus-infected patients undergoing NS3 protease inhibitor monotherapy. J. Clin. Microbiol. 2012, 50:3267-3274.
55. Tong X., Le P.S., Li L., Haines K., Piso K., Baronas V., Yan J.M., So S.S., Klumpp K., Najera I. In vivo emergence of a novel mutant L159F/L320F in the NS5B polymerase confers low-level resistance to the HCV polymerase inhibitors mericitabine and sofosbuvir. J. Infect. Dis. 2014, 209:668-675.
56. Verbinnen T., Van M.H., Vandenbroucke I., Vijgen L., Claes M., Lin T.I., Simmen K., Neyts J., Fanning G., Lenz O. Tracking the evolution of multiple in vitro hepatitis C virus replicon variants under protease inhibitor selection pressure by 454 deep sequencing. J. Virol. 2010, 84:11124-11133.
57. WHO. 2014. http://www.who.int/mediacentre/factsheets/fs164/en/.
58. Wu S., Kanda T., Nakamoto S., Jiang X., Miyamura T., Nakatani S.M., Ono S.K., Takahashi-Nakaguchi A., Gonoi T., Yokosuka O. Prevalence of hepatitis C virus subgenotypes 1a and 1b in Japanese patients: ultra-deep sequencing analysis of HCV NS5B genotype-specific region. PLoS One 2013, 8:e73615.
59. Young K.C., Lindsay K.L., Lee K.J., Liu W.C., He J.W., Milstein S.L., Lai M.M. Identification of a ribavirin-resistant NS5B mutation of hepatitis C virus during ribavirin monotherapy. Hepatology 2003, 38:869-878.
60. Zeuzem S. Clinical implications of hepatitis C viral kinetics. J. Hepatol. 1999, 31(Suppl. 1):S61-S64.
61. Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinform. 2008, 9:40.