Whole genome analysis of hepatitis B virus before and during long-term therapy in chronic infected patients: Molecular characterization, impact on treatment and liver disease progression.
HBV
PCR
Sanger sequencing
antiviral resistance
hepatocellular carcinoma
liver cirrhosis
whole genome
Journal
Frontiers in microbiology
ISSN: 1664-302X
Titre abrégé: Front Microbiol
Pays: Switzerland
ID NLM: 101548977
Informations de publication
Date de publication:
2022
2022
Historique:
received:
15
08
2022
accepted:
15
09
2022
entrez:
3
11
2022
pubmed:
4
11
2022
medline:
4
11
2022
Statut:
epublish
Résumé
Hepatitis B virus (HBV) infection remains a serious public health concern worldwide despite the availability of an efficient vaccine and the major improvements in antiviral treatments. The aim of the present study is to analyze the mutational profile of the HBV whole genome in ETV non-responder chronic HBV patients, in order to investigate antiviral drug resistance, immune escape, and liver disease progression to Liver Cirrhosis (LC) or Hepatocellular Carcinoma (HCC). Blood samples were collected from five chronic hepatitis B patients. For each patient, two plasma samples were collected, before and during the treatment. Whole genome sequencing was performed using Sanger technology. Phylogenetic analysis comparing the studied sequences with reference ones was used for genotyping. The mutational profile was analyzed by comparison with the reference sequence M32138. Genotyping showed that the studied strains belong to subgenotypes D1, D7, and D8. The mutational analysis showed high genetic variability. In the RT region of the polymerase gene, 28 amino acid (aa) mutations were detected. The most significant mutations were the pattern rtL180M + rtS202G + rtM204V, which confer treatment resistance. In the S gene, 35 mutations were detected namely sP120T, sT126S, sG130R, sY134F, sS193L, sI195M, and sL216stop were previously described to lead to vaccine, immunotherapy, and/or diagnosis escape. In the C gene, 34 mutations were found. In particular, cG1764A, cC1766G/T, cT1768A, and cC1773T in the BCP; cG1896A and cG1899A in the precore region and cT12S, cE64D, cA80T, and cP130Q in the core region were associated with disease progression to LC and/or HCC. Other mutations were associated with viral replication increase including cT1753V, cG1764A/T, cC1766G/T, cT1768A, and cC1788G in the BCP as well as cG1896A and cG1899A in the precore region. In the X gene, 30 aa substitutions were detected, of which substitutions xT36D, xP46S, xA47T, xI88F, xA102V, xI127T, xK130M, xV131I, and xF132Y were previously described to lead to LC and/or HCC disease progression. In conclusion, our results show high genetic variability in the long-term treatment of chronic HBV patients causing several effects. This could contribute to guiding national efforts to optimize relevant HBV treatment management in order to achieve the global hepatitis elimination goal by 2030.
Identifiants
pubmed: 36325017
doi: 10.3389/fmicb.2022.1020147
pmc: PMC9618822
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1020147Informations de copyright
Copyright © 2022 Belaiba, Ayouni, Gdoura, Kammoun Rebai, Touzi, Sadraoui, Hammemi, Yacoubi, Abdelati, Hamzaoui, Msaddak Azzouz, Chouikha and Triki.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Natl Cancer Inst. 2009 Aug 5;101(15):1066-82
pubmed: 19574418
Virus Res. 2011 Jan;155(1):254-8
pubmed: 20970466
World J Gastroenterol. 2014 May 14;20(18):5427-34
pubmed: 24833873
BMC Infect Dis. 2018 Jun 1;18(1):251
pubmed: 29859062
J Clin Virol. 2012 Feb;53(2):130-4
pubmed: 22078148
Antivir Ther. 2008;13(3):341-8
pubmed: 18572746
J Hepatol. 1999 May;30(5):749-54
pubmed: 10365797
Liver Int. 2012 Nov;32(10):1535-42
pubmed: 22882650
Viruses. 2020 Jul 06;12(7):
pubmed: 32640609
Intervirology. 2003;46(3):157-63
pubmed: 12867753
Hepat Mon. 2015 May 23;15(5):e25749
pubmed: 26045705
Epidemiol Infect. 2000 Aug;125(1):169-74
pubmed: 11057973
Hepatology. 2007 Dec;46(6):1810-20
pubmed: 17847074
Wellcome Open Res. 2020 Jun 29;5:151
pubmed: 33869791
Clin Microbiol Infect. 2015 Jul;21(7):710.e11-20
pubmed: 25882358
Int J Clin Exp Med. 2015 Jun 15;8(6):9630-9
pubmed: 26309637
Kobe J Med Sci. 2019 Jun 17;65(1):E28-E35
pubmed: 31341154
J Korean Med Sci. 2010 Feb;25(2):257-64
pubmed: 20119580
J Med Virol. 2012 Nov;84(11):1719-26
pubmed: 22997074
J Clin Microbiol. 2005 Dec;43(12):6000-6
pubmed: 16333089
J Hepatol. 2006 Feb;44(2):422-31
pubmed: 16364492
Electron Physician. 2017 Apr 25;9(4):4114-4123
pubmed: 28607644
J Infect Dev Ctries. 2017 Sep 30;11(9):727-732
pubmed: 31600164
J Med Virol. 1994 Sep;44(1):96-103
pubmed: 7798892
Am J Gastroenterol. 2008 Sep;103(9):2254-62
pubmed: 18844615
J Gen Virol. 2008 Apr;89(Pt 4):901-909
pubmed: 18343830
Antimicrob Agents Chemother. 2010 Feb;54(2):882-9
pubmed: 19933798
Mol Clin Oncol. 2016 Jun;4(6):1045-1051
pubmed: 27284442
J Zhejiang Univ Sci B. 2005 Jul;6(7):664-7
pubmed: 15973769
World J Gastroenterol. 2005 Aug 14;11(30):4703-8
pubmed: 16094714
Mol Med Rep. 2015 Oct;12(4):5141-8
pubmed: 26165271
Liver Int. 2007 Dec;27(10):1356-63
pubmed: 17900245
Turk J Pediatr. 2018;60(5):514-519
pubmed: 30968634
J Virol. 2010 Jan;84(2):1026-33
pubmed: 19889778
Infect Genet Evol. 2008 May;8(3):306-12
pubmed: 18372221
World J Gastroenterol. 2017 Jun 21;23(23):4222-4232
pubmed: 28694662
J Med Virol. 2013 Apr;85(4):597-601
pubmed: 23359331
Medicine (Baltimore). 2018 Oct;97(43):e12883
pubmed: 30412082
Clin Microbiol Infect. 2012 Oct;18(10):E412-8
pubmed: 22827722
Antimicrob Agents Chemother. 2004 Sep;48(9):3498-507
pubmed: 15328117
Jpn J Infect Dis. 2017 Nov 22;70(6):647-655
pubmed: 29093313
J Hepatol. 2006 Mar;44(3):593-606
pubmed: 16455151
Hepat Mon. 2013 Jan 20;13(1):e6712
pubmed: 23596461
J Virol. 2003 Jun;77(12):6601-12
pubmed: 12767980
Viruses. 2019 Aug 24;11(9):
pubmed: 31450544
J Gen Virol. 2009 Jul;90(Pt 7):1622-1628
pubmed: 19339480
PLoS Med. 2005 Jul;2(7):e163
pubmed: 16033304
Am J Transplant. 2003 Jun;3(6):743-53
pubmed: 12780567
Emerg Microbes Infect. 2013 Mar;2(3):e10
pubmed: 26038454
Cancer Epidemiol. 2012 Aug;36(4):369-74
pubmed: 22178505
J Clin Diagn Res. 2017 Aug;11(8):DD04-DD06
pubmed: 28969126
Middle East J Dig Dis. 2011 Mar;3(1):13-9
pubmed: 25197527
Pathol Res Pract. 2008;204(10):731-42
pubmed: 18597951
J Gen Virol. 2016 Oct;97(10):2643-2656
pubmed: 27473751
J Med Virol. 2006 Mar;78(3):353-7
pubmed: 16419125
J Med Virol. 2009 May;81(5):815-25
pubmed: 19319945
PLoS One. 2013 Nov 12;8(11):e80346
pubmed: 24265811
World J Gastroenterol. 2008 Sep 21;14(35):5448-53
pubmed: 18803358
Hepat Mon. 2016 Jul 25;16(10):e37806
pubmed: 27882062
Hepatology. 2010 Jun;51(6):1933-44
pubmed: 20512987
Am J Gastroenterol. 2011 Jan;106(1):81-92
pubmed: 20959817
Antivir Chem Chemother. 2001 Jan;12(1):1-35
pubmed: 11437320
Hepatology. 2002 Aug;36(2):464-73
pubmed: 12143057
J Med Virol. 2019 Apr;91(4):615-622
pubmed: 30345529
World J Gastroenterol. 2019 Oct 14;25(38):5883-5896
pubmed: 31636479
Diagn Microbiol Infect Dis. 2014 May;79(1):25-30
pubmed: 24630522
J Hepatol. 2007 Mar;46(3):531-8
pubmed: 17239478
J Viral Hepat. 2008 Oct;15(10):753-60
pubmed: 18507754
PLoS One. 2017 Jul 7;12(7):e0180447
pubmed: 28686707
Intervirology. 2016;59(1):36-47
pubmed: 27544241
Hepat Mon. 2015 Oct 28;15(10):e31490
pubmed: 26587040
Indian J Med Microbiol. 2019 Jul-Sep;37(3):387-392
pubmed: 32003338
J Gen Virol. 2010 Jun;91(Pt 6):1609-20
pubmed: 20147517
J Gen Virol. 2005 Sep;86(Pt 9):2451-2458
pubmed: 16099903
Intervirology. 2012;55(1):36-44
pubmed: 21311172
Antivir Ther. 2005;10(5):625-33
pubmed: 16152756
J Gastroenterol Hepatol. 2008 Mar;23(3):474-81
pubmed: 18318825
PLoS One. 2013;8(1):e54486
pubmed: 23349904
Int J Med Sci. 2005;2(1):2-7
pubmed: 15968333
World J Gastroenterol. 2016 Jun 28;22(24):5467-78
pubmed: 27350725
PLoS One. 2014 Mar 14;9(3):e92223
pubmed: 24632784
J Clin Microbiol. 2004 Jun;42(6):2455-60
pubmed: 15184419
Biomed Rep. 2019 Oct;11(4):145-153
pubmed: 31565220
Antivir Ther. 2009;14(5):649-54
pubmed: 19704167
J Infect Dis. 2014 May 1;209(9):1374-81
pubmed: 24273041
Hepatology. 2004 Jan;39(1):64-73
pubmed: 14752824
J Med Virol. 2012 Feb;84(2):207-16
pubmed: 22170539
World J Gastroenterol. 2016 Jan 7;22(1):145-54
pubmed: 26755866
Front Cell Infect Microbiol. 2018 Oct 22;8:355
pubmed: 30406036
J Med Microbiol. 2021 Mar;70(3):
pubmed: 33704041
J Hepatol. 2017 Dec;67(6):1281-1297
pubmed: 28736138
J Infect. 2007 Mar;54(3):291-7
pubmed: 16911832
Sci Rep. 2015 Dec 09;5:17950
pubmed: 26647737
World J Gastroenterol. 2018 Apr 28;24(16):1708-1724
pubmed: 29713126
J Viral Hepat. 2006 Jul;13(7):427-34
pubmed: 16792535
PLoS One. 2014 Oct 15;9(10):e110012
pubmed: 25333524
J Hepatol. 2019 Jun;70(6):1093-1102
pubmed: 30794889
PLoS One. 2014 May 01;9(5):e94864
pubmed: 24788140
World J Gastroenterol. 2014 Aug 14;20(30):10238-48
pubmed: 25132741
PLoS One. 2014 Feb 28;9(2):e90432
pubmed: 24587360
Hepatology. 2003 Jul;38(1):96-103
pubmed: 12829991
J Med Virol. 2014 May;86(5):745-57
pubmed: 24532489
Antiviral Res. 2010 Mar;85(3):512-9
pubmed: 20034521
Gastroenterology. 2004 Nov;127(5):1356-71
pubmed: 15521005
Antivir Ther. 2011;16(1):37-49
pubmed: 21311107
J Clin Virol. 2020 Aug;129:104548
pubmed: 32663786
J Hepatol. 2009 Oct;51(4):647-54
pubmed: 19586679
Intervirology. 2007;50(1):45-51
pubmed: 17164557
Med Microbiol Immunol. 2007 Dec;196(4):247-52
pubmed: 17503077
J Virol. 2013 Feb;87(4):2352-7
pubmed: 23221548
ScientificWorldJournal. 2013 Nov 04;2013:212704
pubmed: 24302857
J Antimicrob Chemother. 2008 Apr;61(4):766-8
pubmed: 18218641
PLoS One. 2012;7(8):e42891
pubmed: 22905181
Ann Hepatol. 2019 Jul - Aug;18(4):640-645
pubmed: 31105017
Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):590-4
pubmed: 19190166
Hepat Mon. 2013 Oct 15;13(10):e11781
pubmed: 24348634
Mol Biol Evol. 2016 Jul;33(7):1870-4
pubmed: 27004904
Trans R Soc Trop Med Hyg. 2019 Aug 1;113(8):437-445
pubmed: 31574151
Semin Liver Dis. 2003 Feb;23(1):5-20
pubmed: 12616447
Clin Exp Hepatol. 2019 May;5(2):161-168
pubmed: 31501793
J Antimicrob Chemother. 2003 May;51(5):1085-9
pubmed: 12697634
Hepatol Res. 2008 Dec;38(12):1194-203
pubmed: 18624719
Hepatology. 2007 Feb;45(2):277-85
pubmed: 17256766
Oncotarget. 2017 Nov 6;8(62):105115-105125
pubmed: 29285238
Antimicrob Agents Chemother. 2007 Dec;51(12):4533, author reply 4533-4
pubmed: 18025122
World J Gastroenterol. 2014 Jan 14;20(2):425-35
pubmed: 24574711
J Gastroenterol Hepatol. 2016 Oct;31(10):1750-1756
pubmed: 26992056
PLoS One. 2012;7(6):e38394
pubmed: 22675557
Virology. 2002 Feb 15;293(2):305-13
pubmed: 11886250
PLoS One. 2014 Jun 05;9(6):e99028
pubmed: 24901840
Hepat Mon. 2013 Oct 01;13(10):e12160
pubmed: 24348637
Virol J. 2005 Aug 04;2:60
pubmed: 16080797
World J Gastroenterol. 2013 Dec 28;19(48):9294-306
pubmed: 24409056
World J Hepatol. 2015 Nov 28;7(27):2729-39
pubmed: 26644816
J Viral Hepat. 2018 Oct;25(10):1121-1131
pubmed: 29660214
Gastroenterology. 2011 Oct;141(4):1412-21, 1421.e1-5
pubmed: 21704589
Virology. 2002 Jul 20;299(1):88-99
pubmed: 12167344
Mol Med Rep. 2017 May;15(5):3292-3300
pubmed: 28339094
Clin Lab. 2004;50(3-4):159-62
pubmed: 15074469
J Antimicrob Chemother. 2007 Aug;60(2):341-9
pubmed: 17567633
World J Gastroenterol. 2012 Nov 14;18(42):6096-105
pubmed: 23155338