Apoptosis of hepatitis B virus infected hepatocytes prevents release of infectious virus.

[Guest guest]

J Virol. 2010 Aug 18. [Epub ahead of print]

Apoptosis of hepatitis B virus infected hepatocytes prevents release of

infectious virus.

Arzberger S, Hösel M, Protzer U.

Institute of Virology, Technische Universität München/Helmholtz Zentrum München,

Trogerstr. 30, D-81675 Munich, Germany; Molecular

Infectiology at the Center for Molecular Medicine Cologne (ZMMK), Institute for

Medical Microbiology, Immunology and Hygiene, University of Cologne,

f-Stelzmann-Str. 19-21, D-50935 Koeln, Germany.

Abstract

Apoptosis of infected cells is critically involved in antiviral defence.

Apoptosis, however, may also support the release and spread of viruses. Although

elimination of infected hepatocytes is required to combat hepatitis B virus

(HBV) infection, it is still unknown which consequences hepatocyte apoptosis has

for the virus and whether or not it is advantageous for the virus. To study

this, we designed a cell culture model consisting of both HBV-producing cell

lines and primary human hepatocytes serving as an infection model. We showed

that the release of mature, enveloped virions was 80 to 90 % reduced 24 h after

induction of apoptosis in HBV replicating hepatoma cells or HBV infected

hepatocytes. Importantly, HBV particles released from apoptotic hepatocytes were

immature and non-enveloped and proved not to be infectious. We found an inverse

correlation between the strength of an apoptotic stimulus and infectivity of the

virus particles released: the more potent the apoptotic stimulus, the higher was

the ratio of non-enveloped capsids to virions, and the lower was their

infectivity. Furthermore, we demonstrated that HBV replication and particularly

expression of the HBx protein transcribed from the viral genome during

replication does not sensitize cells towards apoptosis. Our data clearly reject

the hypothesis that apoptosis of infected hepatocytes facilitates propagation of

HBV. They rather indicate that HBV needs to prevent apoptosis of its host

hepatocyte to ensure the release of infectious progeny and thus virus spread in

the liver.

PMID: 20719950

[Guest guest]

J Virol. 2010 Aug 18. [Epub ahead of print]

Apoptosis of hepatitis B virus infected hepatocytes prevents release of

infectious virus.

Arzberger S, Hösel M, Protzer U.

Institute of Virology, Technische Universität München/Helmholtz Zentrum München,

Trogerstr. 30, D-81675 Munich, Germany; Molecular

Infectiology at the Center for Molecular Medicine Cologne (ZMMK), Institute for

Medical Microbiology, Immunology and Hygiene, University of Cologne,

f-Stelzmann-Str. 19-21, D-50935 Koeln, Germany.

Abstract

Apoptosis of infected cells is critically involved in antiviral defence.

Apoptosis, however, may also support the release and spread of viruses. Although

elimination of infected hepatocytes is required to combat hepatitis B virus

(HBV) infection, it is still unknown which consequences hepatocyte apoptosis has

for the virus and whether or not it is advantageous for the virus. To study

this, we designed a cell culture model consisting of both HBV-producing cell

lines and primary human hepatocytes serving as an infection model. We showed

that the release of mature, enveloped virions was 80 to 90 % reduced 24 h after

induction of apoptosis in HBV replicating hepatoma cells or HBV infected

hepatocytes. Importantly, HBV particles released from apoptotic hepatocytes were

immature and non-enveloped and proved not to be infectious. We found an inverse

correlation between the strength of an apoptotic stimulus and infectivity of the

virus particles released: the more potent the apoptotic stimulus, the higher was

the ratio of non-enveloped capsids to virions, and the lower was their

infectivity. Furthermore, we demonstrated that HBV replication and particularly

expression of the HBx protein transcribed from the viral genome during

replication does not sensitize cells towards apoptosis. Our data clearly reject

the hypothesis that apoptosis of infected hepatocytes facilitates propagation of

HBV. They rather indicate that HBV needs to prevent apoptosis of its host

hepatocyte to ensure the release of infectious progeny and thus virus spread in

the liver.

PMID: 20719950