Research Article Open Access

Ultrastructural Evidences of Hepatitis B Infection in Human Liver Biopsies Disclose Complex Assembly and Morphogenesis Pathways for Hepatitis B Virus

Viviana Falcon1, Ivon Menéndez1, Nelson Acosta-Rivero1, Mineko Shibayama2, Maria-C de la Rosa1, Jose Luna- Munoz2, Magdalena Miranda-Sanchez2, Jorge V. Gavilondo1, Deliana Lopez1, Santiago Duenas-Carrera1, Bienvenido Gra1, Glay Chinea1, Luisa Tamayo Garcia1, Waldo Garcia3, Eduardo Vidal1, Enrique Arus-Soler1, Jose Silva1, Felix Alvarez1, Emilio F. Acosta2, Jesus Seoane1, Juan Morales-Grillo1, Eduardo Penton1, Juan Kouri2 and Victor Tsutsumi2
  • 1 Institute of Gastroenterology, Cuba
  • 2 Centro de Investigaciones y Estudios Avanzados, Cuba
  • 3 General Hospital, Cuba

Abstract

Despite of recent advances on acknowledge of hepatitis B virus (HBV) structure and biology, little is known about the morphogenesis and release of virions. In this study, the ultrastructural analysis of HBV components in liver biopsies from chronically HBV-infected patients disclosed complex assembly and morphogenesis pathways for HBV. HBV core (HBcAg) and surface (HBsAg) antigens were specifically identified in all liver biopsies from HVB-infected patients. HBcAg containing core-like particles 24-28 nm in diameter were observed both in nucleus and cytoplasm of hepatocytes. Dane’s-like particles were detected either budding to or into the lumen of ER close to HBsAg containing tubular structures. Besides, Dane’s-like particles were detected in different vesicular compartments resembling multivesicular endosomes. Other kind of enveloped HBV-like particles similar to the previously described cobra-shaped and horn-shaped particles were also observed in hepatocytes. Some of these particles were connected to the vesicle membrane through a stalk 20-22 nm in diameter. On the other hand, spherical subviral particles (SVP) were frequently observed in cytoplasmic vesicles. Moreover, a minor proportion of enveloped HBV-like particles budding through the plasma membrane to the extracellular space and bile canaliculi were detected. Interestingly, Dane’s-like particles in the bile canaliculi and entering into ductular-like cells were shown. Strikingly, Dane’s-like particles close to tubular structures and specific immunolabeling for HBcAg both in cytoplasm and nuclei of stellate-like cells were detected. Remarkably, HVB-like particles appeared entering hepatocytes from large cytoplasmic processes of fibrocytes raising the interesting possibility of a cell to cell passage of HBV through direct transcellular migration.

American Journal of Infectious Diseases
Volume 4 No. 2, 2008, 96-103

DOI: https://doi.org/10.3844/ajidsp.2008.96.103

Submitted On: 16 November 2007 Published On: 30 June 2008

How to Cite: Falcon, V., Menéndez, I., Acosta-Rivero, N., Shibayama, M., de la Rosa, M., Luna- Munoz, J., Miranda-Sanchez, M., Gavilondo, J. V., Lopez, D., Duenas-Carrera, S., Gra, B., Chinea, G., Garcia, L. T., Garcia, W., Vidal, E., Arus-Soler, E., Silva, J., Alvarez, F., Acosta, E. F., Seoane, J., Morales-Grillo, J., Penton, E., Kouri, J. & Tsutsumi, V. (2008). Ultrastructural Evidences of Hepatitis B Infection in Human Liver Biopsies Disclose Complex Assembly and Morphogenesis Pathways for Hepatitis B Virus. American Journal of Infectious Diseases, 4(2), 96-103. https://doi.org/10.3844/ajidsp.2008.96.103

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Keywords

  • Hepatitis B virus
  • HBV morphogenesis
  • Dane's particles
  • electron microscopy