Hepatitis B virus

Hepatitis B virus, abbreviated HBV, is a partially double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B. Hepatitis B virus, abbreviated HBV, is a partially double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B. In addition to causing hepatitis, infection with HBV can lead to cirrhosis and hepatocellular carcinoma. It has also been suggested that it may increase the risk of pancreatic cancer. Viral infection by Hepatitis B virus (HBV) causes many hepatocyte changes due to the direct action of a protein encoded by the virus, HBx, and to indirect changes due to a large increase in intracellular reactive oxygen species (ROS) after infection. HBx appears to dysregulate a number of cellular pathways. HBx causes dysregulation in part by binding to genomic DNA, changing expression patterns of miRNAs, affecting histone methyltransferases, binding to SIRT1 protein to activate transcription, and cooperating with histone methylases and demethylases to change cell expression patterns. HBx is partly responsible for the approximate 10,000-fold increase in intracellular ROS upon chronic HBV infection. Increased ROS can be caused, in part, by localization of HBx to the mitochondria where HBx decreases the mitochondrial membrane potential. In addition, another HBV protein, HBsAg, also increases ROS through interactions with the endoplasmic reticulum. The increase in reactive oxygen species (ROS) after HBV infection causes inflammation, which leads to a further increase in ROS. ROS cause more than 20 types of DNA damage. Oxidative DNA damage is mutagenic. In addition, repair of the DNA damage can cause epigenetic alterations at the site of the damage during repair of the DNA. Epigenetic alterations and mutations may cause defects in the cellular machinery that then contribute to liver disease. By the time accumulating epigenetic and mutational changes eventually cause progression to cancer, epigenetic alterations appear to have a larger role in this carcinogenesis than mutations. Only one or two genes, TP53 and perhaps ARID1A, are mutated in more than 20% of liver cancers while 41 genes each have hypermethylated promoters (repressing gene expression) in more than 20% of liver cancers, with seven of these genes being hypermethylated in more than 75% of liver cancers. In addition to alterations at the sites of DNA repair, epigenetic alterations are also caused by HBx recruiting the DNA methyltransferase enzymes, DNMT1 and/or DNMT3A, to specific gene loci to alter their methylation levels and gene expression. HBx also alters histone acetylation that can affect gene expression. Several thousand protein-coding genes appear to have HBx-binding sites. In addition to protein coding genes, about 15 microRNAs and 16 Long non-coding RNAs are also affected by the binding of HBx to their promoters. Each altered microRNA can affect the expression of several hundred messenger RNAs (see microRNA). Hepatitis B virus is classified as the type species of the Orthohepadnavirus, which contains eight other species. The genus is classified as part of the Hepadnaviridae family, which contains one other genus, Avihepadnavirus. This family of viruses have not been assigned to a viral order. Viruses similar to hepatitis B have been found in all apes (orangutan, gibbons, gorillas and chimpanzees), in Old World monkeys, and in a New World woolly monkeys suggesting an ancient origin for this virus in primates. The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes present on its envelope proteins. These serotypes are based on a common determinant (a) and two mutually exclusive determinant pairs (d/y and w/r). The viral strains have also been divided into ten genotypes (A–J) and forty subgenotypes according to overall nucleotide sequence variation of the genome. The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination. The serotypes and genotypes do not necessarily correspond. Genotype D has 10 subgenotypes.