Have you ever wondered why all the characters on The Simpsons are yellow? It seems the entire town of Springfield has been suffering a devastating and extremely widespread outbreak of Hepatitis. Hepatitis is an inflammation of the liver that impedes the liverís function in clearing the body of bilirubin, a breakdown product of the hemoglobin in blood. The accumulation of bilirubin in the body can lead to yellowing of the skin and whites of the eyes, a condition known as jaundice. (Of course that still doesnít account for the blue hair and four fingered freaks that are the Simpson family and their neighbors). Hepatitis can be caused by a number of different agents, including viruses, bacteria, protozoa, pharmaceuticals, and ethanol (alcohol). Many different viruses cause hepatitis including Yellow Fever, Rubella, Reovirus, hemorrhagic fever, some herpesviruses, and a number of different Hepatitis viruses. The Hepatitis viruses, including A, B, C, D, and E, belong to different viral families, are not related, and are transmitted in different ways, although they cause the same syndrome. Hepatitis A virus is a picornavirus transmitted fecal-orally. It mainly causes an acute infection from which most people recover quickly. Hepatitis B virus is transmitted parenterally, sexually, and vertically and it causes acute infection in the majority of cases, but it can also lead to chronic hepatitis, or worse, fulminant hepatitis and death. Hepatitis C presents similarly to B. It is usually less severe, yet leads to chronic infection more frequently. HBV and HCV can also lead to cirrhosis of the liver or hepatocellular carcinoma (HCC), a cancer of the liver. This is more likely to happen in HBV cases. Hepatitis D virus is the most interesting of all!
HDV is replicated in the nucleus by host cell DNA dependent RNA polymerase II via the "rolling circle" method, producing linear strings that are cleaved by delta virus ribozymes. Ribozymes are enzymes in which the catalytic activity is carried out by RNA. The delta agent is the only known animal virus to have ribozyme activity and the first instance in which host DNA dependent RNA polymerase was seen to use RNA as a template. The host polymerase begins RNA synthesis and passes the poly-A signal and self-cleavage domain. Some of the new (+) strands are then processed by cellular enzymes to be polyadenylated mRNA, which is used to produce the delta antigen. The other portion continues RNA synthesis beyond the cleavage point until the RNA undergoes self-cleavage, producing a (+) copy of the template, in which the poly-A site is ignored. After completion of the full (+) strand, the RNA undergoes self-ligation to become a circular loop. This (+) strand is then used to produce full length mRNA resulting in full length (-) copies being produced and then released by the ribozymes to self ligate, restoring the (-) sense circular genome. The replication thus results in the delta virus genomic (-) RNA and a (+) copy.
Picture from the WHO Hepatitis D page
HDV is actually a satellite virus of HBV, because HDV requires co-infection with HBV in order to proliferate. HDV is defective and requires the presence of HBV because although infectious HDV is enveloped, the virus does not encode its own envelope proteins. Therefore it borrows the HBV protein HBsAg (HB surface antigen). All three forms of HBsAg (S, M, and L) are found on the envelope of HDV, although S is seen in a much higher ratio. When HDV replicates, it temporarily supresses the production of HBV particles. Assembly can only occur in the presence of HBsAg (from HBV co-infection) and HDAg-L.