Hepatitis B Virus X protein is essential to initiate and maintain virus replication after infection.

[Guest guest]

J Hepatol. 2011 Mar 1. [Epub ahead of print]

Hepatitis B Virus X protein is essential to initiate and maintain virus

replication after infection.

Lucifora J, Arzberger S, Durantel D, Belloni L, Strubin M, Levrero M, Zoulim F,

Hantz O, Protzer U.

Institute of Virology, Technische Universität München / Helmholtz Zentrum

München, Trogerstrasse, 30, 81675 Munich, Germany.

Abstract

BACKGROUND AND AIMS: Molecular biology of Hepatitis B Virus (HBV) has been

extensively studied but the exact role of the hepatitis B X protein (HBx) in the

context of natural HBV infections remains unknown.

METHODS: Primary human hepatocytes and differentiated HepaRG cells allowing

conditional trans complementation of HBx were infected with wild type (HBV(wt))

or HBx deficient (HBV(x-)) HBV particles and establishment of HBV replication

was followed.

RESULTS: We observed that cells inoculated with HBx-deficient HBV particles

(HBV(x-)) did not lead to productive HBV infection contrary to cells inoculated

with wild type HBV particles (HBV(wt)). Although equal amounts of nuclear

covalently closed circular HBV-DNA (cccDNA) demonstrated comparable uptake and

nuclear import, active transcription was only observed from HBV(wt) genomes.

Transcomplementation of HBx was able to rescue transcription from the HBV(x-)

genome and led to antigen and virion secretion even weeks after infection.

Constant expression of HBx was necessary to maintain HBV antigen expression and

replication. Finally, we demonstrated that HBx is not packaged into virions

during assembly but is expressed after infection within the new host cell to

allow epigenetic control of HBV transcription from cccDNA.

CONCLUSIONS: Our results demonstrate that HBx is required to initiate and

maintain HBV replication and highlight HBx as the key regulator during the

natural infection process.Copyright © 2011 European Association for the Study of

the Liver. Published by Elsevier B.V. All rights reserved.

PMID: 21376091 [PubMed - as supplied by publisher]

[Guest guest]

J Hepatol. 2011 Mar 1. [Epub ahead of print]

Hepatitis B Virus X protein is essential to initiate and maintain virus

replication after infection.

Lucifora J, Arzberger S, Durantel D, Belloni L, Strubin M, Levrero M, Zoulim F,

Hantz O, Protzer U.

Institute of Virology, Technische Universität München / Helmholtz Zentrum

München, Trogerstrasse, 30, 81675 Munich, Germany.

Abstract

BACKGROUND AND AIMS: Molecular biology of Hepatitis B Virus (HBV) has been

extensively studied but the exact role of the hepatitis B X protein (HBx) in the

context of natural HBV infections remains unknown.

METHODS: Primary human hepatocytes and differentiated HepaRG cells allowing

conditional trans complementation of HBx were infected with wild type (HBV(wt))

or HBx deficient (HBV(x-)) HBV particles and establishment of HBV replication

was followed.

RESULTS: We observed that cells inoculated with HBx-deficient HBV particles

(HBV(x-)) did not lead to productive HBV infection contrary to cells inoculated

with wild type HBV particles (HBV(wt)). Although equal amounts of nuclear

covalently closed circular HBV-DNA (cccDNA) demonstrated comparable uptake and

nuclear import, active transcription was only observed from HBV(wt) genomes.

Transcomplementation of HBx was able to rescue transcription from the HBV(x-)

genome and led to antigen and virion secretion even weeks after infection.

Constant expression of HBx was necessary to maintain HBV antigen expression and

replication. Finally, we demonstrated that HBx is not packaged into virions

during assembly but is expressed after infection within the new host cell to

allow epigenetic control of HBV transcription from cccDNA.

CONCLUSIONS: Our results demonstrate that HBx is required to initiate and

maintain HBV replication and highlight HBx as the key regulator during the

natural infection process.Copyright © 2011 European Association for the Study of

the Liver. Published by Elsevier B.V. All rights reserved.

PMID: 21376091 [PubMed - as supplied by publisher]

[Guest guest]

J Hepatol. 2011 Mar 1. [Epub ahead of print]

Hepatitis B Virus X protein is essential to initiate and maintain virus

replication after infection.

Lucifora J, Arzberger S, Durantel D, Belloni L, Strubin M, Levrero M, Zoulim F,

Hantz O, Protzer U.

Institute of Virology, Technische Universität München / Helmholtz Zentrum

München, Trogerstrasse, 30, 81675 Munich, Germany.

Abstract

BACKGROUND AND AIMS: Molecular biology of Hepatitis B Virus (HBV) has been

extensively studied but the exact role of the hepatitis B X protein (HBx) in the

context of natural HBV infections remains unknown.

METHODS: Primary human hepatocytes and differentiated HepaRG cells allowing

conditional trans complementation of HBx were infected with wild type (HBV(wt))

or HBx deficient (HBV(x-)) HBV particles and establishment of HBV replication

was followed.

RESULTS: We observed that cells inoculated with HBx-deficient HBV particles

(HBV(x-)) did not lead to productive HBV infection contrary to cells inoculated

with wild type HBV particles (HBV(wt)). Although equal amounts of nuclear

covalently closed circular HBV-DNA (cccDNA) demonstrated comparable uptake and

nuclear import, active transcription was only observed from HBV(wt) genomes.

Transcomplementation of HBx was able to rescue transcription from the HBV(x-)

genome and led to antigen and virion secretion even weeks after infection.

Constant expression of HBx was necessary to maintain HBV antigen expression and

replication. Finally, we demonstrated that HBx is not packaged into virions

during assembly but is expressed after infection within the new host cell to

allow epigenetic control of HBV transcription from cccDNA.

CONCLUSIONS: Our results demonstrate that HBx is required to initiate and

maintain HBV replication and highlight HBx as the key regulator during the

natural infection process.Copyright © 2011 European Association for the Study of

the Liver. Published by Elsevier B.V. All rights reserved.

PMID: 21376091 [PubMed - as supplied by publisher]

[Guest guest]

J Hepatol. 2011 Mar 1. [Epub ahead of print]

Hepatitis B Virus X protein is essential to initiate and maintain virus

replication after infection.

Lucifora J, Arzberger S, Durantel D, Belloni L, Strubin M, Levrero M, Zoulim F,

Hantz O, Protzer U.

Institute of Virology, Technische Universität München / Helmholtz Zentrum

München, Trogerstrasse, 30, 81675 Munich, Germany.

Abstract

BACKGROUND AND AIMS: Molecular biology of Hepatitis B Virus (HBV) has been

extensively studied but the exact role of the hepatitis B X protein (HBx) in the

context of natural HBV infections remains unknown.

METHODS: Primary human hepatocytes and differentiated HepaRG cells allowing

conditional trans complementation of HBx were infected with wild type (HBV(wt))

or HBx deficient (HBV(x-)) HBV particles and establishment of HBV replication

was followed.

RESULTS: We observed that cells inoculated with HBx-deficient HBV particles

(HBV(x-)) did not lead to productive HBV infection contrary to cells inoculated

with wild type HBV particles (HBV(wt)). Although equal amounts of nuclear

covalently closed circular HBV-DNA (cccDNA) demonstrated comparable uptake and

nuclear import, active transcription was only observed from HBV(wt) genomes.

Transcomplementation of HBx was able to rescue transcription from the HBV(x-)

genome and led to antigen and virion secretion even weeks after infection.

Constant expression of HBx was necessary to maintain HBV antigen expression and

replication. Finally, we demonstrated that HBx is not packaged into virions

during assembly but is expressed after infection within the new host cell to

allow epigenetic control of HBV transcription from cccDNA.

CONCLUSIONS: Our results demonstrate that HBx is required to initiate and

maintain HBV replication and highlight HBx as the key regulator during the

natural infection process.Copyright © 2011 European Association for the Study of

the Liver. Published by Elsevier B.V. All rights reserved.

PMID: 21376091 [PubMed - as supplied by publisher]