Hepatitis B Virus Protein X Induces Degradation of Talin-1.

Maarten Van De Klundert,Maartje Van Den Biggelaar,Hans Zaaijer,Neeltje Kootstra

doi:10.3390/v8100281

Maarten Van De Klundert, Maartje Van Den Biggelaar + Show 2 more

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https://doi.org/10.3390/v8100281

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Journal: Viruses	Publication Date: Oct 19, 2016
Citations: 88	License type: CC BY 4.0

Affiliation: Sanquin, Academic Medical Center, University of Amsterdam

Abstract

In the infected human hepatocyte, expression of the hepatitis B virus (HBV) accessory protein X (HBx) is essential to maintain viral replication in vivo. HBx critically interacts with the host damaged DNA binding protein 1 (DDB1) and the associated ubiquitin ligase machinery, suggesting that HBx functions by inducing the degradation of host proteins. To identify such host proteins, we systematically analyzed the HBx interactome. One HBx interacting protein, talin-1 (TLN1), was proteasomally degraded upon HBx expression. Further analysis showed that TLN1 levels indeed modulate HBV transcriptional activity in an HBx-dependent manner. This indicates that HBx-mediated TLN1 degradation is essential and sufficient to stimulate HBV replication. Our data show that TLN1 can act as a viral restriction factor that suppresses HBV replication, and suggest that the HBx relieves this restriction by inducing TLN1 degradation.

Highlights

Hepatitis B virus (HBV) is a member of the Hepadnaviridae family, and infects hepatocytes in the human liver
Regarding the attenuated replication after transfection of R9∆HBx, hepatitis B virus (HBV) replication could be restored by cotransfection of our pHSV-HBx vector, showing that functional HBx is expressed from this vector [35] (Figure 1A)
HBx interacts with damaged DNA binding protein 1 (DDB1), a host protein often “hijacked” by viral accessory proteins to induce the degradation of a host protein that interferes with viral replication [22,23,24,25,26,27,28,29,30,31,33]

Summary

Introduction

Hepatitis B virus (HBV) is a member of the Hepadnaviridae family, and infects hepatocytes in the human liver. The core particle releases the partially double stranded HBV DNA genome in the nucleus, where it is subsequently repaired by host enzymes to form the HBV covalently closed circular DNA (cccDNA). This circular DNA template of about 3200 base pairs encodes one accessory protein called X (HBx). HBx expression is essential to initiate and maintain HBV replication in vivo [1,2,3,4]. In most hepatoma-derived cell lines, such as HepG2 cells, HBx expression stimulates HBV transcription but is not essential [11,13,14,15]

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