title: Hepatitis B Virus Protein X Induces Degradation of Talin-1.
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.
authors: Department of Blood-borne Infections, Sanquin Research, 1006 AD Amsterdam, The Netherlands.|Department of Experimental Immunology, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors: Maarten A A
authors: MA
authors: van de Klundert
authors: Department of Plasma Proteins, Sanquin Research, 1006 AD Amsterdam, The Netherlands. m.vandenbiggelaar@sanquin.nl.
authors: Maartje
authors: M
authors: van den Biggelaar
authors: Department of Experimental Immunology, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. n.a.kootstra@amc.uva.nl.
authors: Neeltje A
authors: NA
authors: Kootstra
authors: Department of Blood-borne Infections, Sanquin Research, 1006 AD Amsterdam, The Netherlands. h.l.zaaijer@amc.uva.nl.
authors: Hans L
authors: HL
authors: Zaaijer
mesh_terms: D002460:Cell Line; D006515:Hepatitis B virus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D059748:Proteolysis; D016608:Talin / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C518832:TLN1 protein, human; D016608:Talin; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: HBV; HBV transcription; HBx; TLN1; hepatitis B virus; protein X; viral restriction