LIPID INFILTRATION OF HEPATOCYTES IN THE MORPHOGENESIS OF CHRONIC HEPATITIS C
https://doi.org/10.15372/SSMJ20190419
Abstract
The aim of the study was to investigate structurally functional features of lipidic infiltration of hepatocytes in a morphogenesis of chronic hepatitis C. Material and methods. A clinical and morphological study of 199 patients with HCV infection markers (139 men and 60 women aged from 20 till 65 years) was conducted. In all cases, a comprehensive study including analysis of blood biochemical parameters, serological markers of HCV replication in blood and liver, viremia level, number of the infected hepatocytes and HCV genotypes was performed. Diagnostic complex included clinical, biochemical, immunoserological methods. Results and discussion. The results of the analysis of structural and functional features of lipid-containing hepatocytes and indicators of replication of virus particles of chronic hepatitis C are provided. For its reproduction HCV enters into complex relationships with the metabolic apparatus of the cell, in which lipid metabolism and related structures – lipid droplets play an important role. The only structural marker that correlates with indicators of virus replication is subcytolemmal small-vesicular lipid infiltration, which can reflect a virus-induced increase in lipid metabolism in the host cell for the effective production of infectious active viral particles.
About the Authors
D. L. NepomnyashchikhRussian Federation
doctor of medical sciences
630091, Novosibirsk, Krasny av., 52
O. A. Postnikova
Russian Federation
doctor of biological sciences
630091, Novosibirsk, Krasny av., 52
E. E. Abramova
Russian Federation
candidate of medical sciences, assistant
630091, Novosibirsk, Krasny av., 52
O. I. Dorovskaya
Russian Federation
630087, Novosibirsk, Nemirovicha-Danchenko str., 130
References
1. Nepomnyashchikh G.I., Aydagulova S.В., Postnikova О.А., Nepomnyashchikh D.L., Nokhrina Zh.V., Vinogradova E.V. Morphogenesis of chronic hepatitis C and infectious-viral cirrhosis. Klinicheskie persperktivy gastroenterologii, gepatologii = Clinical prospects of gastroenterology, hepatology. 2012; (2): 13–21. [In Russian].
2. Ivashkin V.T., Pavlov C.S. Hepatic fibrosis. Moscow: GEОТАР-Меdiа, 2011. 168 p. [In Russian].
3. Nepomnyashchikh G.I., Bakarev M.A., Nepomnyashchikh D.L., Yudanov A.V., Kapustina V.I., Migus’kina E.I., Postnikova О.А., Vinogradova E.V., Nokhrina Zh.V., Savchenko S.А. Role of lipid infiltration of hepatocytes in the morphogenesis of chronic hepatitis C. Bull. Exp. Biol. Med. 2013; 151 (8): 250–254.
4. Nepomnyashchikh G.I., Postnikova О.А., Bakarev M.A., Nepomnyashchikh D.L., Kapustina V.I. Structural and functional features of lipid-containing hepatocytes in hepatitis C. Bull. Exp. Biol. Med. 2012; 153 (5): 751–754.
5. Nepomnyashchikh G.I. Biopsy in hepatology: General pathology and pathomorphology. Moscow, 2014. 192 p. [In Russian].
6. Burlone M.E., Budkowska A. Hepatitis C virus cell entry: role of lipoproteins and cellular receptors. J. Gen. Virol. 2009; 90: 1055–1070.
7. Nepomnyashchikh G.I., Aydagulova S.В., Postnikova О.А., Nepomnyashchikh D.L., Nokhrina Zh.V., Vinogradova E.V. Morphogenesis of chronic hepatitis C and infectious-viral cirrhosis. Klinicheskie persperktivy gastroenterologii, gepatologii = Clinical prospects of gastroenterology, hepatology. 2012; (2): 13–21. [In Russian].
8. Dubuisson J., Helle F., Cocquerel L. Early steps in the hepatitis C virus life cycle. Cell. Microbiol. 2008; 10: 821–827.
9. Nepomnyashchikh G.I., Bakarev M.A., Nepomnyashchikh D.L., Yudanov A.V., Kapustina V.I., Migus’kina E.I., Postnikova О.А., Vinogradova E.V., Nokhrina Zh.V., Savchenko S.А. Role of lipid infiltration of hepatocytes in the morphogenesis of chronic hepatitis C. Bull. Exp. Biol. Med. 2013; 151 (8): 250–254.
10. Masaki T., Suzuki R., Murakami K., Aizaki H., Ishii K., Murayama A., Date T., Matsuura Y., Miyamura T., Wakita T., Suzuki T. Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles. J. Virol. 2008; 82: 7964–7976.
11. Nepomnyashchikh G.I., Postnikova О.А., Bakarev M.A., Nepomnyashchikh D.L., Kapustina V.I. Structural and functional features of lipid-containing hepatocytes in hepatitis C. Bull. Exp. Biol. Med. 2012; 153 (5): 751–754.
12. McLauchlan J. Lipid droplets and hepatitis C virus infection. Biochim. Biophys. Acta. 2009; 1791: 552–559.
13. Burlone M.E., Budkowska A. Hepatitis C virus cell entry: role of lipoproteins and cellular receptors. J. Gen. Virol. 2009; 90: 1055–1070.
14. Miyanari Y., Atsuzawa K., Usuda N., Watashi K., Hishiki T., Zayas M., Bartenschlager R., Wakita T., Hijikata M., Shimotohno K. The lipid droplet is an important organelle for hepatitis C virus production. Nature Cell Biol. 2007; 9: 1089–1097.
15. Dubuisson J., Helle F., Cocquerel L. Early steps in the hepatitis C virus life cycle. Cell. Microbiol. 2008; 10: 821–827.
16. Negro F. Mechanisms and significance of liver steatosis in hepatitis C virus infection. World J. Gastroenterol. 2006; 12: 6756–6765.
17. Masaki T., Suzuki R., Murakami K., Aizaki H., Ishii K., Murayama A., Date T., Matsuura Y., Miyamura T., Wakita T., Suzuki T. Interaction of hepatitis C virus nonstructural protein 5A with core protein is critical for the production of infectious virus particles. J. Virol. 2008; 82: 7964–7976.
18. Ogawa K., Hishiki T., Shimizu Y., Funami K., Sugiyama K., Miyanari Y., Shimotohno K. Hepatitis C virus utilizes lipid droplet for production of infectious virus. Proc. Jpn. Acad. Ser. B. 2009; 85: 217–227.
19. McLauchlan J. Lipid droplets and hepatitis C virus infection. Biochim. Biophys. Acta. 2009; 1791: 552–559.
20. Popescu C.I., Dubuisson J. Role of lipid metabolism in hepatitis C virus assembly and entry. Biol. Cell. 2010; 102: 63–74.
21. Miyanari Y., Atsuzawa K., Usuda N., Watashi K., Hishiki T., Zayas M., Bartenschlager R., Wakita T., Hijikata M., Shimotohno K. The lipid droplet is an important organelle for hepatitis C virus production. Nature Cell Biol. 2007; 9: 1089–1097.
22. Roingeard P., Hourioux C. Hepatitis C virus core protein, lipid droplets and steatosis. J. Viral Hepat. 2008. 157–164.
23. Negro F. Mechanisms and significance of liver steatosis in hepatitis C virus infection. World J. Gastroenterol. 2006; 12: 6756–6765.
24. Von Hahn T., Rice C.M. Hepatitis C virus entry. J. Biol. Chem. 2008; 283: 3689–3693.
25. Ogawa K., Hishiki T., Shimizu Y., Funami K., Sugiyama K., Miyanari Y., Shimotohno K. Hepatitis C virus utilizes lipid droplet for production of infectious virus. Proc. Jpn. Acad. Ser. B. 2009; 85: 217–227.
26. Popescu C.I., Dubuisson J. Role of lipid metabolism in hepatitis C virus assembly and entry. Biol. Cell. 2010; 102: 63–74.
27. Roingeard P., Hourioux C. Hepatitis C virus core protein, lipid droplets and steatosis. J. Viral Hepat. 2008. 157–164.
28. Von Hahn T., Rice C.M. Hepatitis C virus entry. J. Biol. Chem. 2008; 283: 3689–3693.
Review
For citations:
Nepomnyashchikh D.L., Postnikova O.A., Abramova E.E., Dorovskaya O.I. LIPID INFILTRATION OF HEPATOCYTES IN THE MORPHOGENESIS OF CHRONIC HEPATITIS C. Сибирский научный медицинский журнал. 2019;39(4):150-154. (In Russ.) https://doi.org/10.15372/SSMJ20190419