Antibody Development to HCV Alternate Reading Frame Protein in Liver Transplant Candidate and its Computational Analysis

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Abstract

Background: HCV Alternate Reading Frame Protein (ARFP) is a frameshift product of HCV-core encoding. Here, we characterized specific anti-ARFP antibodies in Liver Transplant Candidate (LTC) and chronic HCV-infected patients.

Methods: The ARFP gene was cloned and the recombinant protein was purified using Nickel chromatography and confirmed by western blotting. ELISA was developed using recombinant core-1a, core- 1b, ARFP-1a protein, and 99-residue synthetic ARFP 1b peptide. By several Bioinformatics tools, general properties, immunogenic epitopes, and structures of these proteins were obtained.

Results: The seroprevalence of anti-core and anti-ARFP antibodies was 100% in LTC patients, but only 75.2% and 94.3% of chronic patients had evidence of anti-ARFP and anti-core antibodies, respectively. In-silico results demonstrated physicochemical features, antigen properties and potential interactors that could describe progression toward advanced liver disease.

Conclusion: As the first report, the prevalence of anti-ARFP antibodies in LTC patients is of the order of 100% and titer of anti-ARFP antibody was significantly higher in LTC patients compared to chronic individuals, suggesting the possible role of ARFP in the progression toward advanced liver disease. In addition, docking analysis determined several interactor proteins such as prefoldin 2, cathepsin B, vitronectin, and angiotensinogen that have an important role in progression to chronic infection and liver disease development.

Keywords: HCV, ARFP, LTC, liver transplant candidate patients, bioinformatics, chronic liver disease.

Graphical Abstract

[1]
Khademolhosseini, F. Outcome and characteristics of patients on the liver transplant waiting list: Shiraz experience. Middle East J. Dig. Dis., 2009, 1(2), 63-67.
[http://dx.doi.org/10.15171/middle]
[2]
Sarvari, J.; Mojtahedi, Z.; Kuramitsu, Y.; Fattahi, M.R.; Ghaderi, A.; Nakamura, K.; Erfani, N. Comparative proteomics of sera from HCC patients with different origins. Hepat. Mon., 2014, 14(1)e13103
[PMID: 24497876]
[3]
Sarvari, J.; Mojtahedi, Z.; Taghavi, S.A.; Kuramitsu, Y.; Shamsi Shahrabadi, M.; Ghaderi, A.; Nakamura, K. Differentially expressed proteins in chronic active hepatitis, cirrhosis, and HCC related to HCV infection in comparison with HBV infection: A proteomics study. Hepat. Mon., 2013, 13(7)e8351
[http://dx.doi.org/10.5812/hepatmon.8351] [PMID: 24066001]
[4]
Hashempour, T.; Bamdad, T.; Bergamini, A.; Lavergne, J.P.; Haj-Sheykholeslami, A.; Brakier-Gingras, L.; Ajorloo, M.; Merat, S. F protein increases CD4+CD25+ T cell population in patients with chronic hepatitis C. Pathog. Dis., 2015, 73(4)pii: ftv022
[http://dx.doi.org/10.1093/femspd/ftv022] [PMID: 25862675]
[5]
Moayedi, J. Comparison of IL-28B favorable genotype frequency between healthy and patients infected with HCV. Sci. J. Ilam Uni. Med. Sci., 2018, 26(2), 28-36.http://sjimu.medilam.ac.ir/article-1-4009-en.html
[http://dx.doi.org/ 10.29252/sjimu.26.2.28]
[6]
Hashempoor, T. A decline in anti-core+ 1 antibody titer occurs in successful treatment of patients infected with hepatitis C virus. Jundishapur J. Microbiol., 2018, 11(2)e58294
[http://dx.doi.org/10.5812/jjm.58294]
[7]
Alborzi, A.; Hashempour, T.; Moayedi, J.; Musavi, Z.; Pouladfar, G.; Merat, S. Role of serum level and genetic variation of IL-28B in interferon responsiveness and advanced liver disease in chronic hepatitis C patients. Med. Microbiol. Immunol., 2017, 206(2), 165-174.
[http://dx.doi.org/10.1007/s00430-017-0497-y] [PMID: 28214926]
[8]
Hashempoor, T. A decline in anti-core+1 antibody titer occurs in successful treatment of patients infected with hepatitis C virus. Jundishapur J. Microbiol., 2018, 11(2)e58294
[http://dx.doi.org/10.5812/jjm.58294]
[9]
Mitchell, O.; Gurakar, A. Management of hepatitis C post-liver transplantation: a comprehensive review. J. Clin. Transl. Hepatol., 2015, 3(2), 140-148.
[PMID: 26357641]
[10]
Merat, S.; Rezvan, H.; Nouraie, M.; Jafari, E.; Abolghasemi, H.; Radmard, A.R.; Zaer-rezaii, H.; Amini-Kafiabad, S.; Maghsudlu, M.; Pourshams, A.; Malekzadeh, R.; Esmaili, S. Seroprevalence of hepatitis C virus: The first population-based study from Iran. Int. J. Infect. Dis., 2010, 14(Suppl. 3), e113-e116.
[http://dx.doi.org/10.1016/j.ijid.2009.11.032] [PMID: 20362479]
[11]
Alborzi, A.M.; Bamdad, T.; Davoodian, P.; Hashempoor, T.; Nejatizadeh, A.A.; Moayedi, J. Insights into the role of HCV Plus-/Minus strand RNA, IFN-γ and IL-29 in relapse outcome in patients infected with HCV. Asian Pac. J. Allergy Immunol., 2015, 33(3), 173-181.
[PMID: 26342113]
[12]
Dustin, L.B.L. Innate and adaptive immune responses in chronic HCV infection. Curr. Drug Targets, 2017, 18(7), 826-843.
[http://dx.doi.org/10.2174/1389450116666150825110532] [PMID: 26302811]
[13]
Erfani, N.; Hamedi-Shahraki, M.; Rezaeifard, S.; Haghshenas, M.; Rasouli, M.; Samsami Dehaghani, A. FoxP3+ regulatory T cells in peripheral blood of patients with epithelial ovarian cancer. Iran. J. Immunol., 2014, 11(2), 105-112.
[PMID: 24975967]
[14]
Faghih, Z. Analysis of T cell receptor repertoire based on Vβ chain in patients with breast cancer. Cancer Biomark., 2018, 22(4), 733-745.
[http://dx.doi.org/10.3233/CBM-181295]
[15]
Haghshenas, M.R.; Khademi, B.; Ashraf, M.J.; Ghaderi, A.; Erfani, N. Helper and cytotoxic T-cell subsets (Th1, Th2, Tc1, and Tc2) in benign and malignant salivary gland tumors. Oral Dis., 2016, 22(6), 566-572.
[http://dx.doi.org/10.1111/odi.12496] [PMID: 27120402]
[16]
Li, H.C.; Ma, H.C.; Yang, C.H.; Lo, S.Y. Production and pathogenicity of hepatitis C virus core gene products. World J. Gastroenterol., 2014, 20(23), 7104-7122.
[http://dx.doi.org/10.3748/wjg.v20.i23.7104] [PMID: 24966583]
[17]
Shehat, M.G.; Bahey-El-Din, M.; Kassem, M.A.; Farghaly, F.A.; Abdul-Rahman, M.H.; Fanaki, N.H. Recombinant expression of the Alternate Reading Frame Protein (ARFP) of hepatitis C virus genotype 4a (HCV-4a) and detection of ARFP and anti-ARFP antibodies in HCV-infected patients. Arch. Virol., 2015, 160(8), 1939-1952.
[http://dx.doi.org/10.1007/s00705-015-2465-4] [PMID: 26036563]
[18]
Bain, C.; Parroche, P.; Lavergne, J.P.; Duverger, B.; Vieux, C.; Dubois, V.; Komurian-Pradel, F.; Trépo, C.; Gebuhrer, L.; Paranhos-Baccala, G.; Penin, F.; Inchauspé, G. Memory T-cell-mediated immune responses specific to an alternative core protein in hepatitis C virus infection. J. Virol., 2004, 78(19), 10460-10469.
[http://dx.doi.org/10.1128/JVI.78.19.10460-10469.2004] [PMID: 15367612]
[19]
Cohen, M.; Bachmatov, L.; Ben-Ari, Z.; Rotman, Y.; Tur-Kaspa, R.; Zemel, R. Development of specific antibodies to an ARF protein in treated patients with chronic HCV infection. Dig. Dis. Sci., 2007, 52(9), 2427-2432.
[http://dx.doi.org/10.1007/s10620-006-9630-2] [PMID: 17436105]
[20]
Hashempour, T.; Ajorloo, M.; Bamdad, T.; Merat, S.; Zaer-Rezaee, H.; Fakharzadeh, E.; Asadi, R.; Zamini, H.; Teimouri, A.A. Development of a recombinant based ELISA using specific antibodies to F protein in HCV chronically infected patients-A seroprevalence study. Iran. J. Virol., 2010, 4(1), 1-6.
[http://dx.doi.org/10.21859/isv.4.1.1]
[21]
Branch, A.D. 640 HCV Alternate Reading Frame Proteins (ARFPS) may be virulence factors that help the virus survive adverse conditions. Hepatology, 2003, 38, 468-469.
[http://dx.doi.org/10.1016/S0270-9139(03)80682-1]
[22]
Miladi, A. Prevalence of antibodies to the HCVF (frameshift) protein in patients with chronic hepatitis C and the role of this protein in HCV infection. In: J. Hepatol.,; Elsevier Science BV, [AE Amsterdam, Netherlands.
[23]
Idrees, S.; Ashfaq, U.A.; Zahoor, M.; Ramzan, S. Molecular modeling and interaction studies of HCV core protein. Virol. Mycol., 2013.[In press]. https://www.longdom.org/abstract/molecular-modeling-and-interaction-studies-of-hcv-core-protein-7785.html
[24]
Mathew, S.; Fatima, K.; Fatmi, M.Q.; Archunan, G.; Ilyas, M.; Begum, N.; Azhar, E.; Damanhouri, G.; Qadri, I. Computational docking study of p7 ion channel from HCV genotype 3 and genotype 4 and its interaction with natural compounds. PLoS One, 2015, 10(6)e0126510
[http://dx.doi.org/10.1371/journal.pone.0126510] [PMID: 26030803]
[25]
Lechmann, M.; Ihlenfeldt, H.G.; Braunschweiger, I.; Giers, G.; Jung, G.; Matz, B.; Kaiser, R.; Sauerbruch, T.; Spengler, U. T- and B-cell responses to different hepatitis C virus antigens in patients with chronic hepatitis C infection and in healthy anti-hepatitis C virus--positive blood donors without viremia. Hepatology, 1996, 24(4), 790-795.
[PMID: 8855177]
[26]
Pirisi, M.; Fabris, C.; Toniutto, P.; Vitulli, D.; Soardo, G.; Falleti, E.; Gonano, F.; Ferroni, P.; Gasparini, V.; Bartoli, E. Reactivity to B cell epitopes within hepatitis C virus core protein and hepatocellular carcinoma. Cancer Res., 1995, 55(1), 111-114.
[PMID: 7528637]
[27]
Baclig, M.O.; Gopez-Cervantes, J.; Natividad, F.F. Bioinformatics tools for identifying hepatitis C virus subtypes. Philipp. J. Sci., 2012, 141(1), 25-34.
[28]
Tailin, G. The bioinformatics analysis of hepatitis C virus E2 protein. In: Int. Conf. Intell. Syst. Knowl. Engr; Atlantis Press, 2007.
[29]
Zarei, M.; Nezafat, N.; Morowvat, M.H.; Ektefaie, M.; Ghasemi, Y. In silico analysis of different signal peptides for secretory production of arginine deiminase in Escherichia coli. Recent Pat. Biotechnol., 2019, 13(3), 217-227.
[http://dx.doi.org/ 10.2174/1872208313666190101114602] [PMID: 30621572]
[30]
Dorosti, H.; Eslami, M.; Negahdaripour, M.; Ghoshoon, M.B.; Gholami, A.; Heidari, R.; Dehshahri, A.; Erfani, N.; Nezafat, N.; Ghasemi, Y. Vaccinomics approach for developing multi-epitope peptide pneumococcal vaccine. J. Biomol. Struct. Dyn., 2018, 37(13), 3524-3535.
[PMID: 30634893]
[31]
Dehghani, B. Functional and structural characterization of Ebola virus glycoprotein (1976-2015)-An in silico study. Int. J. Biomath., 2017, 10(08)1750108
[http://dx.doi.org/10.1142/S179352451750108X]
[32]
Moattari, A.; Dehghani, B.; Khodadad, N.; Tavakoli, F. In silico functional and structural characterization of H1N1 influenza A viruses hemagglutinin, 2010-2013, Shiraz, Iran. Acta Biotheor., 2015, 63(2), 183-202.
[http://dx.doi.org/10.1007/s10441-015-9260-1] [PMID: 25963671]
[33]
Behzad, T.; Dehghani, H.; Zahra, H.; Javad, M. Bioinformatics analysis of domain 1 of HCV-core protein: Iran. Int. J. Pept. Res. Ther., 2019, 1-18. [In press]
[34]
Dehghani, B.; Hashempour, T.; Hasanshahi, Z. Using immunoinformatics and structural approaches to design a novel HHV8 vaccine. Int. J. Pept. Res. Ther., 2019, 1-18.
[35]
Behzad, D.; Tayebeh, H.; Zahra, H. Interaction of human herpesvirus 8 viral interleukin-6 with human interleukin-6 receptor using in silico approach: the potential role in HHV-8 pathogenesis. Curr. Proteomics, 2019, 16, 1-1.
[36]
Hosseini, S.Y.; Sabahi, F.; Moazzeni, S.M.; Modarressi, M.H.; Saberi Firoozi, M.; Ravanshad, M. Construction and preparation of three recombinant adenoviruses expressing truncated NS3 and core genes of hepatitis C virus for vaccine purposes. Hepat. Mon., 2012, 12(8)e6130
[http://dx.doi.org/10.5812/hepatmon.6130] [PMID: 23087750]
[37]
Geourjon, C.; Deléage, G. SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Comput. Appl. Biosci., 1995, 11(6), 681-684.
[http://dx.doi.org/10.1093/bioinformatics/11.6.681] [PMID: 8808585]
[38]
Kelley, L.A.; Mezulis, S.; Yates, C.M.; Wass, M.N.; Sternberg, M.J. The Phyre2 web portal for protein modeling, prediction and analysis. Nat. Protoc., 2015, 10(6), 845-858.
[http://dx.doi.org/10.1038/nprot.2015.053] [PMID: 25950237]
[39]
Chen, C-C.; Hwang, J-K.; Yang, J-M. (PS)2-v2: Template-based protein structure prediction server. BMC Bioinformatics, 2009, 10(1), 366.
[http://dx.doi.org/10.1186/1471-2105-10-366] [PMID: 19878598]
[40]
Yang, J.; Yan, R.; Roy, A.; Xu, D.; Poisson, J.; Zhang, Y. The I-TASSER Suite: Protein structure and function prediction. Nat. Methods, 2015, 12(1), 7-8.
[http://dx.doi.org/10.1038/nmeth.3213] [PMID: 25549265]
[41]
Benkert, P.; Biasini, M.; Schwede, T. Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics, 2011, 27(3), 343-350.
[http://dx.doi.org/10.1093/bioinformatics/btq662] [PMID: 21134891]
[42]
Doytchinova, I.A.; Flower, D.R. Bioinformatic approach for identifying parasite and fungal candidate subunit vaccines. Open Vaccine J., 2008, 1(1), 4.
[http://dx.doi.org/10.2174/1875035400801010022]
[43]
Jespersen, M.C.; Peters, B.; Nielsen, M.; Marcatili, P. BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res., 2017, 45(W1), W24-W29.
[http://dx.doi.org/10.1093/nar/gkx346] [PMID: 28472356]
[44]
Saha, S.; Raghava, G.P. Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins, 2006, 65(1), 40-48.
[http://dx.doi.org/10.1002/prot.21078] [PMID: 16894596]
[45]
Iakoucheva, L.M.; Radivojac, P.; Brown, C.J.; O’Connor, T.R.; Sikes, J.G.; Obradovic, Z.; Dunker, A.K. The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Res., 2004, 32(3), 1037-1049.
[http://dx.doi.org/10.1093/nar/gkh253] [PMID: 14960716]
[46]
Blom, N.; Gammeltoft, S.; Brunak, S. Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J. Mol. Biol., 1999, 294(5), 1351-1362.
[http://dx.doi.org/10.1006/jmbi.1999.3310] [PMID: 10600390]
[47]
Gupta, R.; Jung, E.; Brunak, S. Prediction of N-glycosylation sites in human proteins. 2004.
[48]
Chauhan, J.S.; Rao, A.; Raghava, G.P. In silico platform for prediction of N-, O- and C-glycosites in eukaryotic protein sequences. PLoS One, 2013, 8(6)e67008
[http://dx.doi.org/10.1371/journal.pone.0067008] [PMID: 23840574]
[49]
Gao, D.Y.; Jin, G.D.; Yao, B.L.; Zhang, D.H.; Gu, L.L.; Lu, Z.M.; Gong, Q.; Lone, Y.C.; Deng, Q.; Zhang, X.X. Characterization of the specific CD4+ T cell response against the F protein during chronic hepatitis C virus infection. PLoS One, 2010, 5(12)e14237
[http://dx.doi.org/10.1371/journal.pone.0014237] [PMID: 21151917]
[50]
Varaklioti, A.; Vassilaki, N.; Georgopoulou, U.; Mavromara, P. Alternate translation occurs within the core coding region of the hepatitis C viral genome. J. Biol. Chem., 2002, 277(20), 17713-17721.
[http://dx.doi.org/10.1074/jbc.M201722200] [PMID: 11884417]
[51]
Walewski, J.L.; Keller, T.R.; Stump, D.D.; Branch, A.D. Evidence for a new hepatitis C virus antigen encoded in an overlapping reading frame. RNA, 2001, 7(5), 710-721.
[http://dx.doi.org/10.1017/S1355838201010111] [PMID: 11350035]
[52]
Xu, Z.; Choi, J.; Yen, T.S.; Lu, W.; Strohecker, A.; Govindarajan, S.; Chien, D.; Selby, M.J.; Ou, J. Synthesis of a novel hepatitis C virus protein by ribosomal frameshift. EMBO J., 2001, 20(14), 3840-3848.
[http://dx.doi.org/10.1093/emboj/20.14.3840] [PMID: 11447125]
[53]
Ajorloo, M.; Bamdad, T.; Hashempour, T.; Alborzi, A.M.; Mozhgani, S.H.; Asadi, R.; Haj-sheykholeslami, A.; Merat, S. Detection of specific antibodies to HCV-ARF/CORE+1 protein in cirrhotic and non-cirrhotic patients with hepatitis C: a possible association with progressive fibrosis. Arch. Iran Med., 2015, 18(5), 304-307.
[PMID: 25959912]
[54]
Dalagiorgou, G.; Vassilaki, N.; Foka, P.; Boumlic, A.; Kakkanas, A.; Kochlios, E.; Khalili, S.; Aslanoglou, E.; Veletza, S.; Orfanoudakis, G.; Vassilopoulos, D.; Hadziyannis, S.J.; Koskinas, J.; Mavromara, P. High levels of HCV core+1 antibodies in HCV patients with hepatocellular carcinoma. J. Gen. Virol., 2011, 92(Pt 6), 1343-1351.
[http://dx.doi.org/10.1099/vir.0.023010-0] [PMID: 21307221]
[55]
Komurian-Pradel, F.; Rajoharison, A.; Berland, J.L.; Khouri, V.; Perret, M.; Van Roosmalen, M.; Pol, S.; Negro, F.; Paranhos-Baccalà, G. Antigenic relevance of F protein in chronic hepatitis C virus infection. Hepatology, 2004, 40(4), 900-909.
[http://dx.doi.org/10.1002/hep.20406] [PMID: 15382175]
[56]
Alam, S.S.; Nakamura, T.; Naganuma, A.; Nozaki, A.; Nouso, K.; Shimomura, H.; Kato, N. Hepatitis C virus quasispecies in cancerous and noncancerous hepatic lesions: The core protein-encoding region. Acta Med. Okayama, 2002, 56(3), 141-147.
[PMID: 12108585]
[57]
Budkowska, A.; Kakkanas, A.; Nerrienet, E.; Kalinina, O.; Maillard, P.; Horm, S.V.; Dalagiorgou, G.; Vassilaki, N.; Georgopoulou, U.; Martinot, M.; Sall, A.A.; Mavromara, P. Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection. PLoS One, 2011, 6(1)e15871
[http://dx.doi.org/10.1371/journal.pone.0015871] [PMID: 21283512]
[58]
Ogata, S.; Nagano-Fujii, M.; Ku, Y.; Yoon, S.; Hotta, H. Comparative sequence analysis of the core protein and its frameshift product, the F protein, of hepatitis C virus subtype 1b strains obtained from patients with and without hepatocellular carcinoma. J. Clin. Microbiol., 2002, 40(10), 3625-3630.
[http://dx.doi.org/10.1128/JCM.40.10.3625-3630.2002] [PMID: 12354856]
[59]
Yeh, C.T.; Lo, S.Y.; Dai, D.I.; Tang, J.H.; Chu, C.M.; Liaw, Y.F. Amino acid substitutions in codons 9-11 of hepatitis C virus core protein lead to the synthesis of a short core protein product. J. Gastroenterol. Hepatol., 2000, 15(2), 182-191.
[http://dx.doi.org/10.1046/j.1440-1746.2000.02066.x] [PMID: 10735543]
[60]
Moradpour, D.; Penin, F.; Rice, C.M. Replication of hepatitis C virus. Nat. Rev. Microbiol., 2007, 5(6), 453-463.
[http://dx.doi.org/10.1038/nrmicro1645] [PMID: 17487147]
[61]
Kushima, Y.; Wakita, T.; Hijikata, M. A disulfide-bonded dimer of the core protein of hepatitis C virus is important for virus-like particle production. J. Virol., 2010, 84(18), 9118-9127.
[http://dx.doi.org/10.1128/JVI.00402-10] [PMID: 20592070]
[62]
Shih, C.M.; Chen, C.M.; Chen, S.Y.; Lee, Y.H. Modulation of the trans-suppression activity of hepatitis C virus core protein by phosphorylation. J. Virol., 1995, 69(2), 1160-1171.
[PMID: 7815494]
[63]
Hunter, T.; Karin, M. The regulation of transcription by phosphorylation. Cell, 1992, 70(3), 375-387.
[http://dx.doi.org/10.1016/0092-8674(92)90162-6] [PMID: 1643656]
[64]
Lu, W.; Ou, J.H. Phosphorylation of hepatitis C virus core protein by protein kinase A and protein kinase C. Virology, 2002, 300(1), 20-30.
[http://dx.doi.org/10.1006/viro.2002.1524] [PMID: 12202202]
[65]
Montaldo, C.; Mattei, S.; Baiocchini, A.; Rotiroti, N.; Del Nonno, F.; Pucillo, L.P.; Cozzolino, A.M.; Battistelli, C.; Amicone, L.; Ippolito, G.; van Noort, V.; Conigliaro, A.; Alonzi, T.; Tripodi, M.; Mancone, C. Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload. Proteomics, 2014, 14(9), 1107-1115.
[http://dx.doi.org/10.1002/pmic.201300422] [PMID: 24616218]
[66]
Kobayashi, J.; Yamada, S.; Kawasaki, H. Distribution of vitronectin in plasma and liver tissue: Relationship to chronic liver disease. Hepatology, 1994, 20(6), 1412-1417.
[http://dx.doi.org/10.1002/hep.1840200606] [PMID: 7527001]
[67]
Huang, Y-P.; Cheng, J.; Zhang, S.L.; Wang, L.; Guo, J.; Liu, Y.; Yang, Y.; Zhang, L.Y.; Bai, G.Q.; Gao, X.S.; Ji, D.; Lin, S.M.; Shao, Q. Screening of hepatocyte proteins binding to F protein of hepatitis C virus by yeast two-hybrid system. World J. Gastroenterol., 2005, 11(36), 5659-5665.
[http://dx.doi.org/10.3748/wjg.v11.i36.5659] [PMID: 16237761]
[68]
Drouet, C.; Bouillet, L.; Csopaki, F.; Colomb, M.G. Hepatitis C virus NS3 serine protease interacts with the serpin C1 inhibitor. FEBS Lett., 1999, 458(3), 415-418.
[http://dx.doi.org/10.1016/S0014-5793(99)01194-1] [PMID: 10570951]
[69]
Corey, K.E.; Shah, N.; Misdraji, J.; Abu Dayyeh, B.K.; Zheng, H.; Bhan, A.K.; Chung, R.T. The effect of angiotensin-blocking agents on liver fibrosis in patients with hepatitis C. Liver Int., 2009, 29(5), 748-753.
[http://dx.doi.org/10.1111/j.1478-3231.2009.01973.x] [PMID: 19220742]
[70]
Abdel-Aziz, A. Angiotensin-1 Converting Enzyme (ACE) insertion/deletion polymorphism in Egyptian patients with coronary artery disease. Int. J. Biochem. Res., 2012, 2, 106-119.
[http://dx.doi.org/10.9734/IJBCRR/2012/1622]
[71]
Guillaud, O. Angiotensin blockade does not affect fibrosis progression in recurrent hepatitis C after liver transplantation. Transplant.Proc.,, Elsevier,. 2013.
[http://dx.doi.org/10.1016/j.transproceed.2013.01.067]
[72]
McCaughan, G.W.; George, J. Fibrosis progression in chronic hepatitis C virus infection. Gut, 2004, 53(3), 318-321.
[http://dx.doi.org/10.1136/gut.2003.026393] [PMID: 14960506]
[73]
Dall’Olio, F.; Malagolini, N.; Chiricolo, M. β -Galactoside α2, 6-sialyltransferase and the sialyl α2, 6-galactosyl-linkage in tissues and cell lines, in Glycobiology Protocols. Springer, 2006, 157-170.
[74]
Kitazume, S.; Oka, R.; Ogawa, K.; Futakawa, S.; Hagiwara, Y.; Takikawa, H.; Kato, M.; Kasahara, A.; Miyoshi, E.; Taniguchi, N.; Hashimoto, Y. Molecular insights into β-galactoside α2,6-sialyltransferase secretion in vivo. Glycobiology, 2009, 19(5), 479-487.
[http://dx.doi.org/10.1093/glycob/cwp003] [PMID: 19150807]
[75]
Gangadharan, B.; Antrobus, R.; Dwek, R.A.; Zitzmann, N. Novel serum biomarker candidates for liver fibrosis in hepatitis C patients. Clin. Chem., 2007, 53(10), 1792-1799.
[http://dx.doi.org/10.1373/clinchem.2007.089144] [PMID: 17702858]
[76]
Gangadharan, B.; Bapat, M.; Rossa, J.; Antrobus, R.; Chittenden, D.; Kampa, B.; Barnes, E.; Klenerman, P.; Dwek, R.A.; Zitzmann, N. Discovery of novel biomarker candidates for liver fibrosis in hepatitis C patients: A preliminary study. PLoS One, 2012, 7(6)e39603
[http://dx.doi.org/10.1371/journal.pone.0039603] [PMID: 22761838]
[77]
Huang, Y.; Li, L.Z.; Zhang, C.Z.; Yi, C.; Liu, L.L.; Zhou, X.; Xie, G.B.; Cai, M.Y.; Li, Y.; Yun, J.P. Decreased expression of zinc-alpha2-glycoprotein in hepatocellular carcinoma associates with poor prognosis. J. Transl. Med., 2012, 10(1), 106.
[http://dx.doi.org/10.1186/1479-5876-10-106] [PMID: 22625427]
[78]
Granato, M.; Lacconi, V.; Peddis, M.; Di Renzo, L.; Valia, S.; Rivanera, D.; Antonelli, G.; Frati, L.; Faggioni, A.; Cirone, M. Hepatitis C virus present in the sera of infected patients interferes with the autophagic process of monocytes impairing their in-vitro differentiation into dendritic cells. Biochim. Biophys. Acta, 2014, 1843(7), 1348-1355.
[http://dx.doi.org/10.1016/j.bbamcr.2014.04.003] [PMID: 24726834]
[79]
Sloane, B.F. Cathepsin B and cystatins: Evidence for a role in cancer progression. Semin. Cancer Biol., 1990, 1(2), 137-152.
[PMID: 2103490]
[80]
Ye, F.; Xin, Z.; Han, W.; Fan, J.; Yin, B.; Wu, S.; Yang, W.; Yuan, J.; Qiang, B.; Sun, W.; Peng, X. Quantitative proteomics analysis of the hepatitis C virus replicon high-permissive and low-permissive cell lines. PLoS One, 2015, 10(11)e0142082
[http://dx.doi.org/10.1371/journal.pone.0142082] [PMID: 26544179]
[81]
Berg, C.P.; Schlosser, S.F.; Neukirchen, D.K.; Papadakis, C.; Gregor, M.; Wesselborg, S.; Stein, G.M. Hepatitis C virus core protein induces apoptosis-like caspase independent cell death. Virol. J., 2009, 6(1), 213.
[http://dx.doi.org/10.1186/1743-422X-6-213] [PMID: 19951438]