Hepatit B Virüsü: Yapı ve Patogenez

Hepatit B virüsü, hepadnaviridae ailesinin bir üyesidir. Bu virüs kronik ve akut hepatit hastalıklarına neden olmaktadır. Hepatit B taşıyıcılarının %17 den fazlası karaciğer kanseri ve siroz açısından yüksek risk taşıyan kronik hastalardır. Çeşitli aşıların mevcut olmasına rağmen, HBV hala dünya genelinde önemli bir sağlık problemidir. Anormal konakçı immün yanıtlarının HBV kalıcılığına katkıda bulunan bir faktör olduğuna ve konakçıdaki persistan viral popülasyonlardaki farklılıkların, çeşitli terapötiklerin yanı sıra antiviral immün yanıtlara karşı duyarlılıkla veya dirençle bağlantılı olabileceğine işaret etmektedir ve bu da HBV tedavisini zorlaştırmaktadır. Hepatit B virüsünün tamamının üretilmesi pratik olarak mümkün olmadığından antijenik yapılar, rekombinant DNA teknolojisi ile elde edilmektedir. Aşı geliştirme söz konusu olduğunda, çeşitli popülasyonlara özgü çeşitli viral alt tiplere atfedilen yerel özellikleri hedefleyen aşılar geliştirme çabalarına yönelik araştırmalara yönlenmek akıllıca olacaktır. HBV alt tipinin ana sınıflandırması 4 serotipe (adr, adw, ayr, and ayw) ayrılır. Türkiye'de en yaygın ve tahminen 3,3 milyon Hepatit B vakası bulunan, ayw serotipidir. Aşı geliştirmeye faydalı olabilecek hedefleri göstermek amacıyla, hepatit B virüsünü ve virüsün patojenitezinde bağışıklık sisteminin rolünü tartışacağız.

Anahtar Kelimeler:

Hepatit B, Aşılar, Enfeksiyon

Hepatitis B Virus: Structure and Pathogenesis

The hepatitis B virus is a member of the hepadnaviridae family. This virus causes chronic and acute hepatitis diseases. More than 17% of hepatitis B carriers are chronic patients at high risk for liver cancer and cirrhosis. Although various vaccines are available, HBV is still a major health problem worldwide. It points out that abnormal host immune responses are a contributing factor to HBV persistence and that differences in persistent viral populations in the host may be associated with susceptibility or resistance to antiviral immune responses as well as various therapeutics, complicating HBV treatment. Since it is practically not possible to produce the whole hepatitis B virus, antigenic structures are obtained by recombinant DNA technology. When it comes to vaccine development, it would be wise to focus research on efforts to develop vaccines that target local traits attributed to various viral subtypes unique to various populations. The main classification of the HBV subtype is divided into 4 serotypes (adr, adw, Ayr, and ayw). The ayw serotype is the most common in Türkiye, with an estimated 3.3 million cases of hepatitis B. We will discuss the hepatitis B virus and the immune system's part in the pathogenesis of viruse, to illustrate targets that could be beneficial for vaccine development.

Keywords:

Hepatitis B, Vaccines, infection,

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Bertoletti A, Ferrari C, Fiaccadori F, Penna A, Margolskee R, Schlicht HJ, Fowler P, Guilhot S, Chisari FV. 1991. HLA class Irestricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proc Natl Acad Sci, 88(23): 10445-10449. DOI: 10.1073/pnas.88.23.10445.
Bozdayı A, Aslan N, Bozdayı G, Türkyılmaz AR, Sengezer T, Wend U, Erkan Ö, Aydemir F, Zakirhodjaev S, Orucov Ş, Bozkaya H, Gerlich W, Karayalçın S, Yurdaydın C, Uzunalimoğlu Ö. 2004. Molecular epidemiology of hepatitis B, C and D viruses in Turkish patients. Arch Virol, 149: 2115–2129 DOI: 10.1007/s00705-004-0363-2.
Brown SE, Stanley C, Howard CR, Zuckerman AJ, Steward MW. 1986. Antibody responses to recombinant and plasma derived hepatitis B vaccines. Br Medic J, 292: 159-161.
Chisari FV, Isogawa M, Wieland SF. 2010. Pathogenesis of hepatitis B virus infection. Pathol Biol, 58: 258-266.
Clem A.S. 2011. Fundamentals of Vaccine Immunology. J Global Infect Diseas, 3(1): 73-78.
Cregg JM, Tschopp JF, Stillman C, Siegel R, Akong M, Craig WS, Buckholz RG, Madden KR, Kellaris PA, Davis GR, Smiley BL, Cruze J, Torregrossa R, Velicȩlebi G, Thill GP. 1987. High–level expression and efficient assembly of hepatitis B surface antigen in the methylotrophic yeast, pichia pastoris. Nat Biotechnol, 5: 479. DOI: 10.1038/nbt0587-479.
Dansako H, Ueda Y, Okumura N. 2016. The cyclic GMP-AMP synthetase-STING signaling pathway is required for both the innate immune response against HBV and the suppression of HBV assembly. FEBS J, 283(1): 144-156.
Emini EA, Ellis RW, Miller WJ, McAleer WJ, Scolnick EM, Gerety RJ. 1986. Production and ımmunological analysis of recombinant hepatitis B vaccine. J Infect, 13: 3-9. DOI: 10.1016/S0163-4453(86)92563-6.
Goldsby R, Kindt TJ, Osborne BA, Kuby J. 2003. Chapter 2: Cells and organs of the ımmune system. W. H. Freeman and Company, New York, US, pp: 24-56.
GPR. 2021. Global progress report on HIV, viral hepatitis and sexually transmitted infections: Accountability for the global health sector strategies 2016–2021: actions for impact 15 July 2021 Global report. URL: https://apps.who.int/iris/bitstream/handle/10665/342808/9789240030985-eng.pdf (erişim tarihi: 17 Ocak 2023).
Gregoire C, Chasson L, Luci C, Tomasello E, Geissmann F, Vivier E, Walzer T. 2007. The trafficking of natural killer cells. Immunol Rev, 220: 169-182.
Gupta RK, Siber GR. 1995. Adjuvants for human vaccine- current status, problems and feature prospects. Vaccine, 13: 1263-1276.
Herrscher C, Roingeard P, Blanchard E. 2020. Hepatitis B virus entry into cells. Cells, 9(6): 1486. DOI: 10.3390/cells9061486.
Hilleman MR, Ellis R. 1986. Vaccines made from recombinant yeast cells. Vaccine, 4: 75-76. DOI: 10.1016/0264-410 X (86)90040-X.
Hilleman MR. 1987. Overview of the pathogenesis, prophylaxis, and therapeusis of viral hepatitis B, with focus on reduction to practical applications. Vaccine, 19: 1837-1848.
Inoue T, Tanaka Y. 2020. Cross-protection of hepatitis B vaccination among different genotypes. Vaccines, 8(3): 456.
Jones LS, Peek LJ, Power J, Markham A, Yazzie B, Middaugh CR. 2005. Effects of adsorption to aluminum salt adjuvants on the structure and stability of model protein antigens. J Biol Chem, 280: 13406-13414.
Karlmark KR, Wasmuth HE, Trautwein C, Tacke F. 2008. Chemokine-directed immune cell infiltration in acute and chronic liver disease. Expert Rev Gastroenterol Hepatol, 2(2): 233-242.
Leonard J. 1981. The ghost of yellow jack. Harvard Mag, 83: 20-27.
Li Y, Zhou J, Li T. 2022. Regulation of the HBV Entry Receptor NTCP and its Potential in Hepatitis B Treatment. Front Mol Biosci, 9: 879817. DOİ: 10.3389/fmolb.2022.879817.
Lunsdorf H, Gurramkonda C, Adnan A, Khanna N, Rinas U. 2011. Virus-like particle production with yeast: Ultrastructural and ımmunocytochemical ınsights into pichia pastoris producing high levels of the hepatitis B surface antigen. Microb Cell Fact, 10: 48. DOI: 10.1186/1475-2859-10-48.
Maepa BM, Roelofse I, Ely A, Arbuthnot P. 2015. Progress and prospects of Anti-HBV gene therapy development. Int J Molec Sci, 16(8): 17589-17610. DOI: 10.3390/ijms160817589.
Maini MK, Boni C, Lee CK, Larrubia JR, Reignat S, Ogg GS, King AS, Herberg J, Gilson R, Alisa A, Williams R, Vergani D, Naoumov NV, Ferrari C, Bertoletti A. 2000. The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med, 191: 1269-1280.
Moss B, Smith GL, Gerin JL, Purcell RH. 1984. Live recombinant vaccinia virus protects chimpanzees against hepatitis B. Nature, 311: 67-69.
Ottone S, Nguyen X, Bazin J, Berard C, Jimenez S, Letourneur O. 2007. Expression of hepatitis B surface antigen major subtypes in pichia pastoris and purification for ın vitro diagnosis. protein expr. Purif, 56: 177-188. DOI: 10.1016/ j.pep.2007.07.008.
Rehermann B, Fowler P, Sidney J, Person J, Redeker A, Brown M, Moss B, Sette A, Chisari FV. 1995. The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J Exp Medic, 181: 1047-1058.
Rehermann B, Nascimbeni M. 2005. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol, 3: 215-229.
Romano L, Zanetti A R. 2022. Hepatitis B Vaccination: A Historical Overview with a Focus on the Italian Achievements. Viruses, 14: 1515. https://doi.org/10.3390/v14071515.
Seaman WE. 2000. Natural killer cells and natural killer T cells. Arthritis Rheum, 43(6): 1204-1217.
Shouval D, Ilan Y, Adler R, Deepet R, Panet A, Even-Chen Z, Gorecki M, Gerlich W H. 1994. Improved immunogenicity in mice of a mammalian cell-derived recombinant hepatitis B vaccine containing pre-S and pre-S2 antigens as compared with conventional yeast-derived vaccines. Vaccine, 12: 1453-1459.
Stephenne J. 1988. Recombinant versus plasma-derived hepatitis B vaccines: Issues of safety, ımmunogenicity and cost-effectiveness. Vaccine, 6: 299-303. DOI: 10.1016/0264-410X (88)90173-9.
Stephenne J. 1990. Development and production aspects of a recombinant yeast-derived hepatitis B vaccine. Vaccine, 8: S69-S73. DOI: 10.1016/0264-410X (90)90221-7.
Tarafdar S, Virata ML, Yan H, Zhong L, Deng L, Xu Y, He Y, Struble E, Zhang P. 2021. Multiple epitopes of hepatitis B virus surface antigen targeted by human plasma‐derived immunoglobulins coincide with clinically observed escape mutations. J Med Virol, 94(2): 649-658. DOI: 10.1002/jmv.27278.
Thimme R, Wieland S, Steiger C, Ghrayeb J, Reimann KA, Purcell RH, Chisari FV. 2003. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. J Virol, 77: 68-76.
Tsui LV, Guidotti LG, Ishikawa T, Chisari FV. 1995. Posttranscriptional clearance of hepatitis B virus RNA by cytotoxic T lymphocyte-activated hepatocytes. Proc Natl Acad Sci, 92: 12398-123402.
Valenzuela P, Medina A, Rutter WJ, Hammerer G, Hall BD. 1982. Synthesis and assembly of hepatitis B virus surface antigen particles in yeast. Nature, 298: 347-350.
Vogel R, Powell MF. 1995. A compendium of vaccine adjuvants and excipients. Pharm Biotechnol, 6: 141-228.
Wei L, Ploss A. 2021. Hepatitis B virus cccDNA is formed through distinct repair processes of each strand. Nat Commun, 12(1): 1-13.
WHO. 2017. World Health Organization. Global Hepatitis Report, Geneva, 2017. URL: https://www.who.int/publications/i/ item/ 9789241565455 (erişim tarihi: 23 Şubat 2023).
Zhang Q, Zhang X, Chen T, Wang X, Fu Y, Jin Y, Sun X, Gong T, Zhang Z. 2015. A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus. Nanoscale, 7(20): 9298-9310. DOI: 10.1039/C4NR04730C.