infectpataogДальневосточный журнал инфекционной патологииFar Eastern Journal of Infectious Pathology2073-2899ФБУН Хабаровский НИИ эпидемиологии и микробиологии Роспотребнадзораinfectpataog-411Research ArticleОБЗОРЫСИСТЕМА АПОПТОЗА FAS/APO-1/CD95 И ЕЕ РОЛЬ В ПАТОГЕНЕЗЕ ВИЧ-ИНФЕКЦИИ И ПАРЕНТЕРАЛЬНЫХ ВИРУСНЫХ ГЕПАТИТОВ (ОБЗОР ЛИТЕРАТУРЫ)FAS/APO-1/CD95 INDUCED APOPTOSIS AND IT’S ROLE IN PATHOGENESIS OF HIV-INFECTION AND PARENTERAL VIRAL HEPATITIS (LITERATURE REVIEW)БазыкинаЕ. A.BazykinaE. A.

Базыкина Елена Анатольевна – научный сотрудник лаборатории эпидемиологии и профилактики ВИЧ-инфекции и вирусных гепатитов

Хабаровск

Khabarovsk

adm@hniiem.ruТроценкоО. Е.TrotsenkoО. Е.

Хабаровск

Khabarovsk

ФБУН Хабаровский НИИ эпидемиологии и микробиологии РоспотребнадзораРоссияFBIS Khabarovsk research institute of epidemiology and microbiology of the Federal service for surveillance on consumers rights protection and human wellbeing (Rospotrebnadzor)Russian Federation2020010620250381318Copyright © Базыкина Е.A., Троценко О.Е., 20252025Базыкина Е.A., Троценко О.Е.Bazykina E.A., Trotsenko О.Е.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://infectpataog.elpub.ru/jour/article/view/411

Обзор литературы посвящен изучению влияния ВИЧ, вирусов парентеральных гепатитов В, С (ВГВ, ВГС) и человеческого пегивируса 1 типа (human pegivirus-1 – HPgV-1), ранее известного как GBV-C или вирусный гепатит G, на систему апоптоза. При инфицировании человека ВИЧ, ВГВ и ВГС происходит дисрегуляция процессов апоптоза, что считается одним из звеньев патогенеза как состояний, спровоцированных указанными возбудителями, так и различных неопластических процессов. Обсуждается влияние дисрегуляции системы апоптоза на развитие поражения печени и возникновение гепатоцеллюлярной карциномы, вызванной ВГС. В отличие от других вирусов HPgV-1 обладает благоприятным влиянием на течение ВИЧ-инфекции, что связано с многими процессами, происходящими в организме инфицированного пациента, например, с изменением синтеза хемокинов группы RANTES, влиянием антител к белку E2 HPgV-1 на ход инфекционного процесса. Особый упор сделан на изучении влияния Fas-индуцированного пути апоптоза, являющегося основным патогенетическим звеном ВИЧ-инфекции, ведущим к лавинообразной гибели CD4+ лимфоцитов. Обсуждается влияние белков ВИЧ (gp 120, Vpr, Nef) на прогрессию заболевания. Углубленное изучение механизмов, лежащих в основе нарушения запрограммированной гибели клеток, может привести к созданию новых подходов в диагностике и лечении различных патологических процессов, в частности, ВИЧ-инфекции и вирусных гепатитов.

The current literature review highlights the issues concerning influence of HIV and hepatitis B and C viruses (HBV, HCV), human pegivirus type 1 (HPgV-1) previously known as GBV-C or hepatitis G virus on programmed cell death. Different infections such as HIV, HBV and HCV can provoke dysregulation in apoptosis, which is known to play a part in their pathogenesis as well as induce neoplastic processes in human organism. The article discusses influence of disruption of apoptosis on liver injury and hepatic hepatocellular carcinoma formation specifically induced by HCV. Unlike other viruses, HPgV-1 infection process can favor HIV-infection course. For example, it is known that HPgV-1 alters HIV-infection state due to induction of RANTES chemokines and HPgV-1 viral E2 glycoprotein secretion. Particular emphasis was drawn on the Fas-induced apoptosis that is a fundamental part of HIV pathogenesis and triggers massive death of CD4+ lymphocytes. Influence of HIV proteins (gp 120, Vpr, Nef) on progression of the disease was also discussed. A thorough study of mechanisms that induce disruption of programmed cell death can lead to invention of innovative approaches of diagnosis and treatment of variety of pathologic processes including HIVinfection and viral hepatitis.

ВИЧ-инфекцияпарентеральные вирусные гепатитыапоптозHIV infectionviral hepatitisapoptosisReferencesБобкова МР. «Иммунитет и ВИЧ-инфекция». - М.: Олимпия Пресс, 2006. - 240 с.Бобкова МР. «Иммунитет и ВИЧ-инфекция». - М.: Олимпия Пресс, 2006. - 240 с.Жаворонок СВ, Москалева НВ, Тумаш ОЛ, Барышников АЮ. Перспективы килинико-лабораторного использования растворимой формы антигена CD95 // Наука и инновации. – 2014. – № 3, Vol. 133. - P. 67-72.Жаворонок СВ, Москалева НВ, Тумаш ОЛ, Барышников АЮ. Перспективы килинико-лабораторного использования растворимой формы антигена CD95 // Наука и инновации. – 2014. – № 3, Vol. 133. - P. 67-72.Лаврик И, Краммер П. Решение «жизнь-или-смерть» в системе CD95: основные про- и антиапоптозные модуляторы // ACTA NATURAE. – 2009. –№ l. - Р.80-83Лаврик И, Краммер П. Решение «жизнь-или-смерть» в системе CD95: основные про- и антиапоптозные модуляторы // ACTA NATURAE. – 2009. –№ l. - Р.80-83Москалева НВ. Растворимая форма Fas/Apo-1-антигена в периферической крови при ВИЧинфекции / Н. В. Москалева, С. В. Жаворонок, О. Л. Тумаш // Актуальные вопросы инфекционной патологии: 6-й съезд инфекционистов Республики Беларусь, Витебск, 29-30 мая 2014 г. - Витебск: ВГМУ, 2014. - С. 129-130.Москалева НВ. Растворимая форма Fas/Apo-1-антигена в периферической крови при ВИЧинфекции / Н. В. Москалева, С. В. Жаворонок, О. Л. Тумаш // Актуальные вопросы инфекционной патологии: 6-й съезд инфекционистов Республики Беларусь, Витебск, 29-30 мая 2014 г. - Витебск: ВГМУ, 2014. - С. 129-130.Arokium H, Kamata M, Chen I. Virion-associated Vpr of human immunodeficiency virus type 1 triggers activation of apoptotic events and enhances Fas-induced apoptosis in human T cells // J Virol. – 2009. – № 83. Vol. 21. – P. 11283-11297. doi: 10.1128/JVI.00756-09;Arokium H, Kamata M, Chen I. Virion-associated Vpr of human immunodeficiency virus type 1 triggers activation of apoptotic events and enhances Fas-induced apoptosis in human T cells // J Virol. – 2009. – № 83. Vol. 21. – P. 11283-11297. doi: 10.1128/JVI.00756-09;Balasubramanian A, Koziel M, Groopman JE, Ganju RK. Molecular mechanism of hepatic injury in coinfection with hepatitis C virus and HIV // Clin Infect Dis. Suppl 1– 2005. – № 41. – P. 32–S37. doi:10.1086/429493Balasubramanian A, Koziel M, Groopman JE, Ganju RK. Molecular mechanism of hepatic injury in coinfection with hepatitis C virus and HIV // Clin Infect Dis. Suppl 1– 2005. – № 41. – P. 32–S37. doi:10.1086/429493Balestrieri E, Grelli S, Matteucci C, et al. Apoptosis-associated gene expression in HIV-infected patients in response to successful antiretroviral therapy // J Med Virol. – 2007. – № 79, Vol. 2. – P. 111-117. doi: 10.1002/jmv.20768.Balestrieri E, Grelli S, Matteucci C, et al. Apoptosis-associated gene expression in HIV-infected patients in response to successful antiretroviral therapy // J Med Virol. – 2007. – № 79, Vol. 2. – P. 111-117. doi: 10.1002/jmv.20768.Chavan SJ, Tamma SL, Kaplan M, et al. Reduction in T cell apoptosis in patients with HIV disease following antiretroviral therapy // Clin Immunol. – 1999. – № 93, Vol. 1. – P. 24-33. doi: 10.1006/clim.1999.4770.Chavan SJ, Tamma SL, Kaplan M, et al. Reduction in T cell apoptosis in patients with HIV disease following antiretroviral therapy // Clin Immunol. – 1999. – № 93, Vol. 1. – P. 24-33. doi: 10.1006/clim.1999.4770.Dockrell DH, Badley AD, Algeciras-Schimnich A, et al. Activation-induced CD4+ T cell death in HIV-positive individuals correlates with Fas susceptibility, CD4+ T cell count, and HIV plasma viral copy number // AIDS Res Hum Retroviruses. – 1999. – № 15, Vol 17. – p. 1509-1518. doi: 10.1089/088922299309793.Dockrell DH, Badley AD, Algeciras-Schimnich A, et al. Activation-induced CD4+ T cell death in HIV-positive individuals correlates with Fas susceptibility, CD4+ T cell count, and HIV plasma viral copy number // AIDS Res Hum Retroviruses. – 1999. – № 15, Vol 17. – p. 1509-1518. doi: 10.1089/088922299309793.Ehrhard S, Wernli M, Kaufmann G, et al. Effect of antiretroviral therapy on apoptosis markers and morphology in peripheral lymph nodes of HIV-infected individuals // Infection. – 2008. – №36, Vol. 2. – P. 120- 129. doi: 10.1007/s15010-008-7368-9.Ehrhard S, Wernli M, Kaufmann G, et al. Effect of antiretroviral therapy on apoptosis markers and morphology in peripheral lymph nodes of HIV-infected individuals // Infection. – 2008. – №36, Vol. 2. – P. 120- 129. doi: 10.1007/s15010-008-7368-9.Feuth T, Van Baarle D, Hoepelman AI, et al. Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV-HCV coinfected patients, irrespective of liver disease severity // Apoptosis. – 2014. – № 19, Vol. 7. – P. 1128–1135. doi:10.1007/s10495-014-0992-1Feuth T, Van Baarle D, Hoepelman AI, et al. Activation of extrinsic apoptosis pathway in HCV monoinfected and HIV-HCV coinfected patients, irrespective of liver disease severity // Apoptosis. – 2014. – № 19, Vol. 7. – P. 1128–1135. doi:10.1007/s10495-014-0992-1Fukumori T, Akari H, Yoshida A, et al. Regulation of cell cycle and apoptosis by human immunodeficiency virus type 1 Vpr // Microbes Infect. – 2000. –№ 2, Vol 9. – P. 1011-1017. doi: 10.1016/s1286-4579(00)01255-7.Fukumori T, Akari H, Yoshida A, et al. Regulation of cell cycle and apoptosis by human immunodeficiency virus type 1 Vpr // Microbes Infect. – 2000. –№ 2, Vol 9. – P. 1011-1017. doi: 10.1016/s1286-4579(00)01255-7.Grelli S, Campagna S, Lichtner M, et al. Spontaneous and anti-Fas-induced apoptosis in lymphocytes from HIV-infected patients undergoing highly active anti-retroviral therapy // AIDS. – 2000. - № 14, Vol. 8. – P. 939-949. doi: 10.1097/00002030-200005260-00005.Grelli S, Campagna S, Lichtner M, et al. Spontaneous and anti-Fas-induced apoptosis in lymphocytes from HIV-infected patients undergoing highly active anti-retroviral therapy // AIDS. – 2000. - № 14, Vol. 8. – P. 939-949. doi: 10.1097/00002030-200005260-00005.Hammam O, Mahmoud O, Zahran M et al. The Role of Fas/Fas Ligand System in the Pathogenesis of Liver Cirrhosis and Hepatocellular Carcinoma // Hepatitis Monthly. – 2012. – № 12, Vol. 11: e6132. doi:10.5812/hepatmon.6132Hammam O, Mahmoud O, Zahran M et al. The Role of Fas/Fas Ligand System in the Pathogenesis of Liver Cirrhosis and Hepatocellular Carcinoma // Hepatitis Monthly. – 2012. – № 12, Vol. 11: e6132. doi:10.5812/hepatmon.6132Holm GH, Gabuzda D. Distinct mechanisms of CD4+ and CD8+ T-cell activation and bystander apoptosis induced by human immunodeficiency virus type 1 virions // J Virol. – 2005. – № 79, Vol, 10. – P. 6299-6311. doi: 10.1128/JVI.79.10.6299-6311.2005.Holm GH, Gabuzda D. Distinct mechanisms of CD4+ and CD8+ T-cell activation and bystander apoptosis induced by human immunodeficiency virus type 1 virions // J Virol. – 2005. – № 79, Vol, 10. – P. 6299-6311. doi: 10.1128/JVI.79.10.6299-6311.2005.Ikomey GM, Okomo-Assoumou MC, Atashili J, et al. Plasma concentrations of soluble Fas receptors (Fas) and Fas ligands (FasL) in relation to CD4+ cell counts in HIV-1 positive and negative patients in Yaounde, Cameroon // BMC Res Notes. – 2012. – №5. – Р. 322. doi: 10.1186/1756-0500-5-322.Ikomey GM, Okomo-Assoumou MC, Atashili J, et al. Plasma concentrations of soluble Fas receptors (Fas) and Fas ligands (FasL) in relation to CD4+ cell counts in HIV-1 positive and negative patients in Yaounde, Cameroon // BMC Res Notes. – 2012. – №5. – Р. 322. doi: 10.1186/1756-0500-5-322.Li-Weber M, Weigand MA, Giaisi M, et al. Vitamin E inhibits CD95 ligand expression and protects T cells from activation-induced cell death // J Clin Invest. 2002. – № 110, Vol. 5. – P. 681-690. doi: 10.1172/JCI15073.Li-Weber M, Weigand MA, Giaisi M, et al. Vitamin E inhibits CD95 ligand expression and protects T cells from activation-induced cell death // J Clin Invest. 2002. – № 110, Vol. 5. – P. 681-690. doi: 10.1172/JCI15073.Macias J, Japón MA, Sáez C, et al. Increased hepatocyte Fas expression and apoptosis in HIV and hepatitis C virus coinfection // J Infect Dis. – 2005. – № 192, Vol 9. – P. 1566-1576. doi: 10.1086/491736.Macias J, Japón MA, Sáez C, et al. Increased hepatocyte Fas expression and apoptosis in HIV and hepatitis C virus coinfection // J Infect Dis. – 2005. – № 192, Vol 9. – P. 1566-1576. doi: 10.1086/491736.Matarrese P, Gambardella L, Cassone A, et al. Mitochondrial membrane hyperpolarization hijacks activated T lymphocytes toward the apoptotic-prone phenotype: homeostatic mechanisms of HIV protease inhibitors // J Immunol. - 2003. – № 170, Vol. 12. – P. 6006-6015. doi: 10.4049/jimmunol.170.12.6006.Matarrese P, Gambardella L, Cassone A, et al. Mitochondrial membrane hyperpolarization hijacks activated T lymphocytes toward the apoptotic-prone phenotype: homeostatic mechanisms of HIV protease inhibitors // J Immunol. - 2003. – № 170, Vol. 12. – P. 6006-6015. doi: 10.4049/jimmunol.170.12.6006.Moenkemeyer M, Schmidt RE, Wedemeyer H, et al. GBV-C coinfection is negatively correlated to Fas expression and Fas-mediated apoptosis in HIV-1 infected patients // J Med Virol. – 2008. – № 80, Vol. 11. – P. 1933–1940. doi:10.1002/jmv.21305Moenkemeyer M, Schmidt RE, Wedemeyer H, et al. GBV-C coinfection is negatively correlated to Fas expression and Fas-mediated apoptosis in HIV-1 infected patients // J Med Virol. – 2008. – № 80, Vol. 11. – P. 1933–1940. doi:10.1002/jmv.21305Moretti S, Alesse E, Marcellini S, et al. Combined antiviral therapy reduces HIV-1 plasma load and improves CD4 counts but does not interfere with ongoing lymphocyte apoptosis // Immunopharmacol Immunotoxicol. – 1999. – № 21, Vol. 4. – P. 645-665. doi: 10.3109/08923979909007132.Moretti S, Alesse E, Marcellini S, et al. Combined antiviral therapy reduces HIV-1 plasma load and improves CD4 counts but does not interfere with ongoing lymphocyte apoptosis // Immunopharmacol Immunotoxicol. – 1999. – № 21, Vol. 4. – P. 645-665. doi: 10.3109/08923979909007132.Munshi N, Balasubramanian A, Koziel M, et al. Hepatitis C and human immunodeficiency virus envelope proteins cooperatively induce hepatocytic apoptosis via an innocent bystander mechanism // J Infect Dis. – 2003. – № 188, Vol. 8. – P. 1192–1204. doi:10.1086/378643Munshi N, Balasubramanian A, Koziel M, et al. Hepatitis C and human immunodeficiency virus envelope proteins cooperatively induce hepatocytic apoptosis via an innocent bystander mechanism // J Infect Dis. – 2003. – № 188, Vol. 8. – P. 1192–1204. doi:10.1086/378643Nair MPN, Mahajan S, Hou J, et al. The stress hormone, cortisol, synergizes with HIV-1 gp-120 to induce apoptosis of normal human peripheral blood mononuclear cells // Cell Mol Biol (Noisy-le-grand). – 2000. – № 46, Vol. 7. – P. 1227-1238.Nair MPN, Mahajan S, Hou J, et al. The stress hormone, cortisol, synergizes with HIV-1 gp-120 to induce apoptosis of normal human peripheral blood mononuclear cells // Cell Mol Biol (Noisy-le-grand). – 2000. – № 46, Vol. 7. – P. 1227-1238.O'Connell J, Houston A, Bennett MW, et al. Immune privilege or inflammation Insights into the Fas ligand enigma // Nat. Med. – 2001. – № 7. – Р. 271–274.O'Connell J, Houston A, Bennett MW, et al. Immune privilege or inflammation Insights into the Fas ligand enigma // Nat. Med. – 2001. – № 7. – Р. 271–274.Pan T, Wu S, He X, et al. Necroptosis takes place in human immunodeficiency virus type-1 (HIV1)-infected CD4+ T lymphocytes // PLoS One. – 2014. – № 9, Vol. 4: e93944. doi: 10.1371/journal.pone.0093944.Pan T, Wu S, He X, et al. Necroptosis takes place in human immunodeficiency virus type-1 (HIV1)-infected CD4+ T lymphocytes // PLoS One. – 2014. – № 9, Vol. 4: e93944. doi: 10.1371/journal.pone.0093944.Poonia B., Pauza CD, Salvato MS. Role of the Fas/FasL pathway in HIV or SIV disease // Retrovirology. – 2009. – № 6. – Р. 91. doi:10.1186/1742-4690-6-91.Poonia B., Pauza CD, Salvato MS. Role of the Fas/FasL pathway in HIV or SIV disease // Retrovirology. – 2009. – № 6. – Р. 91. doi:10.1186/1742-4690-6-91.Purevjav E, Nelson DP, Varela JJ, et al. Myocardial Fas ligand expression increases susceptibility to AZT-induced cardiomyopathy // Cardiovasc Toxicol. – 2007. – № 7, Vol. 4. – P. 255-263. doi: 10.1007/s12012-007-9004-9.Purevjav E, Nelson DP, Varela JJ, et al. Myocardial Fas ligand expression increases susceptibility to AZT-induced cardiomyopathy // Cardiovasc Toxicol. – 2007. – № 7, Vol. 4. – P. 255-263. doi: 10.1007/s12012-007-9004-9.Raghuraman S, Abraham P, Daniel HD, et al. Characterization of soluble FAS, FAS ligand and tumor necrosis factor-alpha in patients with chronic HCV infection // J Clin Virol. – 2005. – № 34, Vol 1. – P. 63–70. doi:10.1016/j.jcv.2005.01.009Raghuraman S, Abraham P, Daniel HD, et al. Characterization of soluble FAS, FAS ligand and tumor necrosis factor-alpha in patients with chronic HCV infection // J Clin Virol. – 2005. – № 34, Vol 1. – P. 63–70. doi:10.1016/j.jcv.2005.01.009Restifo NP. Countering the 'counterattack' hypothesis // Nat. Med. – 2001. –№ 7, Vol 3. - P. 259 doi: 10.1038/85357.Restifo NP. Countering the 'counterattack' hypothesis // Nat. Med. – 2001. –№ 7, Vol 3. - P. 259 doi: 10.1038/85357.Roger PM, Breittmayer JP, Durant J, et al; Groupe d'Etudes Niçois Polyvalent en Infectiologie. Early CD4(+) T cell recovery in human immunodeficiency virus-infected patients receiving effective therapy is related to a down-regulation of apoptosis and not to proliferation // J Infect Dis. – 2002. – № 185, Vol. 4. – P. 463-470. doi: 10.1086/338573.Roger PM, Breittmayer JP, Durant J, et al; Groupe d'Etudes Niçois Polyvalent en Infectiologie. Early CD4(+) T cell recovery in human immunodeficiency virus-infected patients receiving effective therapy is related to a down-regulation of apoptosis and not to proliferation // J Infect Dis. – 2002. – № 185, Vol. 4. – P. 463-470. doi: 10.1086/338573.Schwarze-Zander C, Blackard JT, Rockstroh JK. Role of GB virus C in modulating HIV disease // Expert Rev Anti Infect Ther. – 2012. – № 10, Vol. 5. - P. 563–572. doi:10.1586/eri.12.37Schwarze-Zander C, Blackard JT, Rockstroh JK. Role of GB virus C in modulating HIV disease // Expert Rev Anti Infect Ther. – 2012. – № 10, Vol. 5. - P. 563–572. doi:10.1586/eri.12.37Sevilya Z, Chorin E, Gal-Garber O, et al. Killing of Latently HIV-Infected CD4 T Cells by Autologous CD8 T Cells Is Modulated by Nef // Front Immunol. – 2018. – № 9. – P.2068. doi: 10.3389/fimmu.2018.02068. PMID: 30254642;Sevilya Z, Chorin E, Gal-Garber O, et al. Killing of Latently HIV-Infected CD4 T Cells by Autologous CD8 T Cells Is Modulated by Nef // Front Immunol. – 2018. – № 9. – P.2068. doi: 10.3389/fimmu.2018.02068. PMID: 30254642;Shata MTM, Abdel-Hameed EA, Rouster SD, et al. HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles. Version 2 // Pathog Immun. – 2019. – № 4, Vol. 1. – P. 39-65. doi: 10.20411/pai.v4i1.267.Shata MTM, Abdel-Hameed EA, Rouster SD, et al. HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles. Version 2 // Pathog Immun. – 2019. – № 4, Vol. 1. – P. 39-65. doi: 10.20411/pai.v4i1.267.Sieg S, Smith D, Yildirim Z, Kaplan D. Fas ligand deficiency in HIV disease // Proc Natl Acad Sci USA. – 1997. – № 94, Vol. 11. – P. 5860-5865. doi: 10.1073/pnas.94.11.5860.Sieg S, Smith D, Yildirim Z, Kaplan D. Fas ligand deficiency in HIV disease // Proc Natl Acad Sci USA. – 1997. – № 94, Vol. 11. – P. 5860-5865. doi: 10.1073/pnas.94.11.5860.Silvestris F, Cafforio P, Frassanito MA, et al. Overexpression of Fas antigen on T cells in advanced HIV-1 infection: differential ligation constantly induces apoptosis // AIDS. – 1996.– №10, Vol. 2. – P. 131-141. doi: 10.1097/00002030-199602000-00002.Silvestris F, Cafforio P, Frassanito MA, et al. Overexpression of Fas antigen on T cells in advanced HIV-1 infection: differential ligation constantly induces apoptosis // AIDS. – 1996.– №10, Vol. 2. – P. 131-141. doi: 10.1097/00002030-199602000-00002.Strasser A., Jost P.J., Nagata S. The many roles of FAS receptor signaling in the immune system // Immunity. j.immuni. – 2009. – № 30, Vol. 2. – P. 180-192. doi:10.1016/2009.01.001.Strasser A., Jost P.J., Nagata S. The many roles of FAS receptor signaling in the immune system // Immunity. j.immuni. – 2009. – № 30, Vol. 2. – P. 180-192. doi:10.1016/2009.01.001.Wang XZ, Chen XC, Chen YX. Overexpression of HBxAg in hepatocellular carcinoma and its relationship with Fas/FasL system // World J. Gastroenterol. 2003. – № 9, Vol. 12. – P. 2671–2675. doi: 10.3748/wjg.v9.i12.2671.Wang XZ, Chen XC, Chen YX. Overexpression of HBxAg in hepatocellular carcinoma and its relationship with Fas/FasL system // World J. Gastroenterol. 2003. – № 9, Vol. 12. – P. 2671–2675. doi: 10.3748/wjg.v9.i12.2671.Wu NP, Li D, Bader A, et al. Effect of HIV-1 infection on apoptosis of CD4+ T lymphocytes mediated by Fas // Zhejiang Da Xue Xue Bao Yi Xue Ban. – 2003. –№ 32, Vol 2. – P. 90-93.Wu NP, Li D, Bader A, et al. Effect of HIV-1 infection on apoptosis of CD4+ T lymphocytes mediated by Fas // Zhejiang Da Xue Xue Bao Yi Xue Ban. – 2003. –№ 32, Vol 2. – P. 90-93.Xu XN, Laffert B, Screaton GR, et al. Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain // J Exp Med. 1999. – № 189, Vol. 9. – P.1489-1496. doi: 10.1084/jem.189.9.1489.Xu XN, Laffert B, Screaton GR, et al. Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain // J Exp Med. 1999. – № 189, Vol. 9. – P.1489-1496. doi: 10.1084/jem.189.9.1489.

The authors declare that there are no conflicts of interest present.