Ultrastructural Evidences of Hepatitis B Infection in Human Liver Biopsies Disclose Complex Assembly

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American Journal of Infectious Diseases 4 (2): 97-103, 2008

ISSN 1553-6203

© 2008 Science Publications

Corresponding Author: Viviana Falcon, Center for Genetic Engineering and

Biotechnology (CIGB), P.O. Box 6162,

Havana 10600, Cuba

97

Ultrastructural Evidences of Hepatitis B Infection in Human Liver Biopsies

Disclose Complex Assembly and Morphogenesis Pathways for Hepatitis B Virus

1Viviana Falcon, 1Ivon Menéndez, 1 Acosta-Rivero,

4Mineko Shibayama, 1Marýa-C de la , 4 Luna- Munoz,

4Magdalena Miranda-, 1 V. Gavilondo, 1Deliana ,

1Santiago Duenas-Carrera, 2Bienvenido Gra, 1Glay Chinea, 2a Tamayo ,

3Waldo , 2 Vidal, 2Enrique Arus-Soler, 1 Silva, 1Felix Alvarez,

5Emilio F. Acosta, 1Jesus Seoane, 1 Morales-Grillo, 1 Penton,

4 Kouri and 4Victor Tsutsumi

1Centro de Ingeniería Genética y Biotecnología, P.O. Box 6162, C.P. 10600, La

Habana, Cuba

2Institute of Gastroenterology, C.P. 10400, La Havana, Cuba

3General Hospital ‘‘Calixto ’’, C.P. 10400,La Havana, Cuba

4Centro de Investigaciones y Estudios Avanzados (CINVESTAV-IPN), México DF,

Mexico

5Escuela Latinoamericana de Ciencias Médicas, La Habana, 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.

FULL TEXT: http://www.scipub.org/fulltext/ajid/ajid4297-103.pdf

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