Activation of Intracellular Signaling by Hepatitis B and C Viruses: C-Viral Core Is the Most Potent Signal Inducer

[Guest guest]

Hepatology 2000 Aug;32(2):405-412

Activation of Intracellular Signaling by Hepatitis B and C Viruses: C-Viral

Core Is the Most Potent Signal Inducer.

Kato N, Yoshida H, Kioko Ono-Nita S, Kato J, Goto T, Otsuka M, Lan Kh,

Matsushima K, Shiratori Y, Omata M

Department of Gastroenterology, Faculty of Medicine, University of Tokyo,

Tokyo, Japan.

[Record supplied by publisher]

To clarify the effects of hepatitis C virus (HCV) infection on hepatocytes,

we analyzed and compared the induction of intracellular signals by HCV and

hepatitis B virus (HBV) proteins. We examined the influence of 7 HCV (core,

NS2, NS3, NS4A, NS4B, NS5A, and NS5B) and 4 HBV (precore, core, polymerase,

and X) proteins on 5 well-defined intracellular signaling pathways

associated with cell proliferation, differentiation, and apoptosis by use of

a reporter assay. Viral protein-expression vectors were cotransfected into

mammalian cells with reporter vectors having a luciferase gene driven by the

following inducible cis-enhancer elements: the cyclic adenosine

monophosphate response element, the serum response element (SRE), and the

binding sites for nuclear factor kappaB (NF-kappaB), activator protein 1

(AP-1), and serum response factor (SRF). In addition, the activation of

signals by HCV proteins was examined in a reporter plasmid having a natural

interleukin-8 (IL-8) promoter upstream of a luciferase gene. Of 11 HCV and

HBV proteins, HCV core had the strongest influence on intracellular signals,

especially NF-kappaB-, AP-1-, and SRE-associated pathways. HCV core's

activation level exceeded that of HBV X protein, a well-characterized

transactivator of these signals. Moreover, HCV core activated the IL-8

promoter through NF-kappaB and AP-1. For the other proteins, HCV NS4B showed

signal activation, but signals were activated at a lesser extent. The

luciferase reporter assay, a recently introduced technique, helped in the

elucidation of molecular events underlying the inflammatory and

proliferation process in the liver induced by HCV.

PMID: 10915750

[Guest guest]

Hepatology 2000 Aug;32(2):405-412

Activation of Intracellular Signaling by Hepatitis B and C Viruses: C-Viral

Core Is the Most Potent Signal Inducer.

Kato N, Yoshida H, Kioko Ono-Nita S, Kato J, Goto T, Otsuka M, Lan Kh,

Matsushima K, Shiratori Y, Omata M

Department of Gastroenterology, Faculty of Medicine, University of Tokyo,

Tokyo, Japan.

[Record supplied by publisher]

To clarify the effects of hepatitis C virus (HCV) infection on hepatocytes,

we analyzed and compared the induction of intracellular signals by HCV and

hepatitis B virus (HBV) proteins. We examined the influence of 7 HCV (core,

NS2, NS3, NS4A, NS4B, NS5A, and NS5B) and 4 HBV (precore, core, polymerase,

and X) proteins on 5 well-defined intracellular signaling pathways

associated with cell proliferation, differentiation, and apoptosis by use of

a reporter assay. Viral protein-expression vectors were cotransfected into

mammalian cells with reporter vectors having a luciferase gene driven by the

following inducible cis-enhancer elements: the cyclic adenosine

monophosphate response element, the serum response element (SRE), and the

binding sites for nuclear factor kappaB (NF-kappaB), activator protein 1

(AP-1), and serum response factor (SRF). In addition, the activation of

signals by HCV proteins was examined in a reporter plasmid having a natural

interleukin-8 (IL-8) promoter upstream of a luciferase gene. Of 11 HCV and

HBV proteins, HCV core had the strongest influence on intracellular signals,

especially NF-kappaB-, AP-1-, and SRE-associated pathways. HCV core's

activation level exceeded that of HBV X protein, a well-characterized

transactivator of these signals. Moreover, HCV core activated the IL-8

promoter through NF-kappaB and AP-1. For the other proteins, HCV NS4B showed

signal activation, but signals were activated at a lesser extent. The

luciferase reporter assay, a recently introduced technique, helped in the

elucidation of molecular events underlying the inflammatory and

proliferation process in the liver induced by HCV.

PMID: 10915750