American Journal of Infectious Diseases

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

Viviana Falcon, Ivon Menéndez, Nelson Acosta-Rivero, Mineko Shibayama, Maria-C de la Rosa, Jose Luna- Munoz, Magdalena Miranda-Sanchez, Jorge V. Gavilondo, Deliana Lopez, Santiago Duenas-Carrera, Bienvenido Gra, Glay Chinea, Luisa Tamayo Garcia, Waldo Garcia, Eduardo Vidal, Enrique Arus-Soler, Jose Silva, Felix Alvarez, Emilio F. Acosta, Jesus Seoane, Juan Morales-Grillo, Eduardo Penton, Juan Kouri and Victor Tsutsumi

DOI : 10.3844/ajidsp.2008.96.103

American Journal of Infectious Diseases

Volume 4, Issue 2

Pages 96-103

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.

Copyright

© 2008 Viviana Falcon, Ivon Menéndez, Nelson Acosta-Rivero, Mineko Shibayama, Maria-C de la Rosa, Jose Luna- Munoz, Magdalena Miranda-Sanchez, Jorge V. Gavilondo, Deliana Lopez, Santiago Duenas-Carrera, Bienvenido Gra, Glay Chinea, Luisa Tamayo Garcia, Waldo Garcia, Eduardo Vidal, Enrique Arus-Soler, Jose Silva, Felix Alvarez, Emilio F. Acosta, Jesus Seoane, Juan Morales-Grillo, Eduardo Penton, Juan Kouri and Victor Tsutsumi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.