The molecular and pathophysiological implications of hepatitis B X antigen in chronic hepatitis B virus infection

Abstract

Hepatitis B virus is considered one of the most significant environmental carcinogens in humans. Because the mechanisms of HBV replication and the development of hepatocellular carcinoma (HCC) are partially known, HBV-associated pathogenesis remains a challenge to increase its understanding. Evidence suggests that the regulatory protein hepatitis B virus X (HBx) mediates the establishment and maintenance of the chronic carrier state. HBx is a multifunctional and potentially oncogenic protein that is conserved among mammalian hepadnaviruses; it is produced very early after infection and throughout the chronic phase. HBx exerts its effects by interacting with cellular proteins and activating various signaling pathways. HBx stimulates the transcription of genes that regulate cell growth, apoptosis, and DNA repair. It also interacts with proteasome subunits and affects mitochondrial stability. Moreover, HBx participates in processes that are associated with the progression of chronic liver disease, including angiogenesis and fibrosis. This review discusses the function of HBx in the life cycle of HBV and its contribution to the pathogenesis of HCC.

Hepatitis B virus–triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response

“…[30][31][32][33][34] Indeed, HBx can alter the expression patterns of apoptosis-related genes to promote cell survival and persistence of the carrier state. 6,7 In the current study, we found that TNFRSF10B degradation induced by HBx leads to the downregulation of its cell surface expression with no effect on the expression of other apoptosis-related proteins such as CASP8, FADD, BIRC3/cIAP2 (baculoviral IAP repeat containing 3), CFLAR/c-FLIP (CASP8 and FADD like apoptosis regulator), and MCL1 (BCL2 family apoptosis regulator) (Fig. S3).…”

“…12,13,24 The essential function of HBx in HBV replication and liver inflammation is well known. 6,7 HBx is a multifunctional protein that affects multiple events in infected cells, including signal transduction, proteasome activity, cell proliferation, and apoptosis. 6,7,[25][26][27][28][29] Numerous lines of evidence suggest that HBx contributes to protection of infected hepatocytes from immune-mediated destruction.…”

“…6,7 HBx is a multifunctional protein that affects multiple events in infected cells, including signal transduction, proteasome activity, cell proliferation, and apoptosis. 6,7,[25][26][27][28][29] Numerous lines of evidence suggest that HBx contributes to protection of infected hepatocytes from immune-mediated destruction. 6,7 This function of HBx is mediated by the activation of intracellular signaling pathways dependent on NFKB (nuclear factor kappa B), MAPK8/JNK1 (mitogen-activated protein kinase 8), and PDPK1/PKB kinase (3-phosphoinositide dependent protein kinase 1), which promote growth and survival of infected cells.…”

“…6,7,[25][26][27][28][29] Numerous lines of evidence suggest that HBx contributes to protection of infected hepatocytes from immune-mediated destruction. 6,7 This function of HBx is mediated by the activation of intracellular signaling pathways dependent on NFKB (nuclear factor kappa B), MAPK8/JNK1 (mitogen-activated protein kinase 8), and PDPK1/PKB kinase (3-phosphoinositide dependent protein kinase 1), which promote growth and survival of infected cells. [30][31][32][33][34] Indeed, HBx can alter the expression patterns of apoptosis-related genes to promote cell survival and persistence of the carrier state.…”

“…5 HBV X protein (HBx) is an essential viral protein that is required for successful replication and maintenance of viral infection in mouse models and various cultured cell systems. 6,7 HBx can induce autophagy in liver cell lines by upregulating BECN1 (Beclin 1) expression. 8 HBx can trigger autophagy by directly interacting with the class III phosphatidylinositol 3-kinase (PtdIns3K) to favor virus replication.…”