Hepatitis B virus HBx protein - medicalspirit

[ArchivalUser]

some one please explain am not to clear about HBX- is it good or bad
HBX is it helping Hepatistus B virus bc it supresses P53 gene??
HbX prevents viral replication?

http://www.pnas.org/content/94/16/8744.abstract

Please let me know..

[ArchivalUser]

from UW:
HBV encodes for Hbx protein, a substance that distrupts growth control of infected cells by activating multiple growth promoting gene. HbX protein also binds to P53 , apprantly impeding it's growth suppressing activities..

some one please elaborate.......... Not to clear to me.

[ArchivalUser]

Persistent infection with hepatitis B virus (HBV) is a leading cause of human liver disease and is strongly associated with hepatocellular carcinoma, one of the most prevalent forms of human cancer. Apoptosis (programmed cell death) is an important mediator of chronic liver disease caused by HBV infection. It is demonstrated that the HBV HBx protein acutely sensitizes cells to apoptotic killing when expressed during viral replication in cultured cells and in transfected cells independently of other HBV genes. Cells that were resistant to apoptotic killing by high doses of tumor necrosis factor α (TNFα, a cytokine associated with liver damage during HBV infection, were made sensitive to very low doses of TNFα by HBx. HBx induced apoptosis by prolonged stimulation of N-Myc and the stress-mediated mitogen-activated-protein kinase kinase 1 (MEKK1) pathway but not by up-regulating TNF receptors. Cell killing was blocked by inhibiting HBx stimulation of N-Myc or mitogen-activated-protein kinase kinase 1 using dominant-interfering forms or by retargeting HBx from the cytoplasm to the nucleus, which prevents HBx activation of cytoplasmic signal transduction cascades. Treatment of cells with a mitogenic growth factor produced by many virus-induced tumors impaired induction of apoptosis by HBx and TNFα. These results indicate that HBx might be involved in HBV pathogenesis (liver disease) during virus infection and that enhanced apoptotic killing by HBx and TNFα might select for neoplastic hepatocytes that survive by synthesizing mitogenic growth factors.

[ArchivalUser]

I think : Since p53 regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer.
Hbx by inhibiting p53 is causing pathology in hepatocellular carcinoma.

????

[ArchivalUser]

The viral protein HbX activates the synthesis of insulin like growth factor 2 and receptors for insulin like growth factor 1, thereby stimulating cell proliferation.

[ArchivalUser]

nice one!
thanks

[ArchivalUser]

in addition...
HBx is a hepatitis B viral protein.
The protein is 154 amino acids long and interferes with transcription, signal transduction, cell cycle progress, protein degradation, apoptosis and chromosomal stability in the host.

+ HBx activate Ras-RAf MAP kinase signal cascade--->activates transcription factors AP-1 and NF-kappa B, and stimulates cell DNA synthesis.
+ HBx also increase activate CDK2 and CDC2----> activate cyclin E,A,B
+ HBx activate and increase synthesis insulin-like GF2 and receptor of insulin-like GF 1--->activate cell proliferation
+ HBx bind to p53, degenarate P53 and impede its activities/cell control

HBV intergated viral DNA into host cell genome considered trigger the neoplasm,
pathogenesis still unclear...