HBV Signaling

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Abstract

Infection with hepatitis B virus (HBV) continues to be a major health problem with about 400 million people chronically infected worldwide who are at high risk of developing liver cirrhosis and hepatocellular carcinoma (HCC) [1].

HBV is a member of the Hepadnaviridae family which includes small enveloped DNA viruses infecting primates, rodents, and birds [2,3]. One common characteristic of these viruses is their high species and cell-type specificity, as well as a unique genomic organization and replication mechanism. The genome of all hepadnaviruses is extremely compact consisting of four overlapping open reading frames (ORF). The S, Core and Pol ORFs encode viral proteins that are essential structural components of viral replication and assembly (envelope proteins (SHBs, MHBs and LHBs), core (HBc) and reverse transcriptase (RT)/polymerase (Pol)). The HBeAg, which is generated by the intracellular processing of the preC/Core protein at the endoplasmic reticulum (ER) levels as well as by intracellular and extracellular proteolysis of free HBc proteins, is thought to play an important role in HBV pathogenesis by influencing the host immune system . The X ORF encodes for the regulatory X protein (hepatitis B virus X protein (HBx)) which is an essential factor for viral replication and it is considered to be one of the most important determinants of HBV-induced hepatocarcinogenesis [4]. Whereas many aspects of viral replication have been elucidated, the initial phases of hepadnaviral infection (attachment of mature virions onto host cell membranes and viral entry) are still less understood, and the search for putative cellular receptors and coreceptors is still very active. An additional important feature of hepadnaviruses replication is the relative low fidelity of the ­enzimatic machinery that leads to high genomic heterogeneity and variability [2,3].

Keywords

Basal Core Promoter cccDNA Formation 
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© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Dipartimento di Medicina InternaSapienza Universita’ di RomaRomeItaly

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