Hepatitis B virus molecular biology and pathogenesis

Abstract

As obligate intracellular parasites, viruses need a host cell to provide a milieu favorable to viral replication. Consequently, viruses often adopt mechanisms to subvert host cellular signaling processes. While beneficial for the viral replication cycle, virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis, including, for oncogenic viruses, cell transformation and cancer progression. Included among these oncogenic viruses is the hepatitis B virus (HBV). Despite the availability of an HBV vaccine, 350–500 million people worldwide are chronically infected with HBV, and a significant number of these chronically infected individuals will develop hepatocellular carcinoma (HCC). Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC. Globally, HCC is the second highest cause of cancer-associated deaths, underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC. HBV is the prototype member of the Hepadnaviridae family; members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts. The extremely small and compact hepadnaviral genome, the unique arrangement of open reading frames, and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae. In this review, we provide a comprehensive description of HBV biology, summarize the model systems used for studying HBV infections, and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC. For example, the HBV X protein (HBx), a key regulatory HBV protein that is important for HBV replication, is thought to play a cofactor role in the development of HBV-induced HCC, and we highlight the functions of HBx that may contribute to the development of HBV-associated HCC.

Study on the relationship of demographic characteristics of rs1053004 in STAT3 Gene in pationts with HCC following chronic HBV infection

“…In other words, the variable of age could have a predictive role in development of HCC. Lamontagne in a study stated that development of a HBVpositive chronic infection is related to the age of the patients, in a way that younger patients are at more risks for developing this infection (27). Results of the present study are in line with the results of Lamontagne study.…”

Chronic hepatitis B and non‐alcoholic fatty liver disease: Conspirators or competitors?

“…Accumulating evidence has shown the promotive role of HBx in hepatic steatosis. HBx is an HBV‐encoded 17 kDa regulatory protein that is involved with HBV replication and carcinogenesis . It was initially found to promote intracellular lipid accumulation through β1,4‐N‐acetylglucosaminyltransferase‐III‐mediated inhibition of ApoB secretion .…”

“…HBx is an HBV-encoded 17 kDa regulatory protein that is involved with HBV replication and carcinogenesis. 90 It was initially found to promote intracellular lipid accumulation through β1,4-N-acetylglucosaminyltransferase-III-mediated inhibition of ApoB secretion. 91 HBx-mediated upregulation of CCAAT enhancer binding protein (C/EBP) expression and activity.…”

The Regulatory Role of MicroRNA in Hepatitis-B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) Pathogenesis

“…In this disrupted tissue, HBV-HCC may develop from cells that are able to survive in cirrhotic livers and that are more resistant to adverse conditions, viral infection, and apoptosis [18]. In this regard, the HBx protein is thought to play a key role in the development of HCC because it can inhibit the TP53 function in early carcinogenesis, and may contribute to the accumulation of aberrant replacement cells by downregulating apoptosis [18,140]. The HBx transactivating protein promotes cell cycle progression, inactivates negative growth regulators, tumor suppressors, and senescence-related factors [141,142].…”