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Chapter 56 : Hepatitis D Virus
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Hepatitis delta virus (HDV) is the only member of the family Deltaviridae, genus Deltavirus. To establish infection in vivo, HDV depends on helper functions provided by hepatitis B virus (HBV). HDV encodes a single protein, the HDAg, which is translated from a 0.8-kb mRNA transcribed from the genomic RNA. The host range of HDV infection includes humans, chimpanzees, woodchucks, and ducks carrying HBV-related hepadnaviruses. A common feature of experimental HDV infection is the inhibition of HBV, shown by a decrease in the levels of HBsAg and HBV DNA in the serum and liver. The liver histologic pattern of hepatitis D is nonspecific and is similar to other types of viral hepatitis. The intralobular inflammatory cells were mainly macrophages containing periodic acid-Schiff-positive nonglycogenic granules. The main strategies for the prevention of HDV infection are (i) behavioral modifications to prevent disease transmission and (ii) active immunization against HBV. Changes in sexual practices in response to human immunodeficiency virus (HIV) infection have probably contributed to the declining incidence of HBV and HDV infection in the developed world and abroad, and improved methods for screening of blood products in blood banks have reduced the risk of transmission-associated hepatitis. HBV antisense oligonucleotides were constructed to alter HBV functions that are considered essential for HDV replication in vitro.
Schematic representation of HDV.
HDV RNA genome structure.
Sequence and secondary structure of the HDV genomic ribozyme. In the left box the specific on/off adaptor (SOFA) delta ribozyme module is shown. BL, blocker; BS, biosensor; ST, stabilizer. A search for ribozymes in the human genome map showed that a ribozyme segment structurally and biochemically related to the HDV ribozyme is contained in a conserved mammalian sequence residing in an intron of the CPEB3 gene, which belongs to a family of genes regulating mRNA polyadenylation ( 107 ). On the basis of these observations, it is thought that HDV ribozymes and the CPEB3 ribozyme are evolutionarily related and that HDV may have arisen from the human transcriptome.
HDAg gene and protein domains. ORF, open reading frame.
Serologic profile of HBV-HDV coinfection.
Serologic course of HDV superinfection evolving to chronicity.
Genotypes of HDV
Progression from chronic HDV hepatitis to cirrhosis and liver dysfunction
Death (free of transplantation) from HDV cirrhosis