Introduction
History
In 1977, an Italian doctor named Mario Rizzetto discovered a new nuclear antigen in the liver cells of patients infected with Hepatitis B Virus (HBV). The antigen was thought to be a new protein encoded by HBV, and it was labeled as the delta antigen. Subsequent research on chimpanzees, however, indicated that this antigen was derived from a new virus, named the Hepatitis Delta Virus (HDV).
Classification
HDV is the only virus in the genus, Deltaviridae. HDV is not classified into a viral family because it is a unique virus dependent on HBV. HDV is a co-infection of HBV. The envelope of HDV particles contains the Hepatitis B surface antigen (HBsAg). The production and transmission of HDV is entirely dependent on HBV to provide HBsAg. Thus, HDV is considered a satellite virus of HBV. Unlike a classical satellite virus, however, HDV does not share sequence similarity with HBV, and it can replicate independently of HBV.
There are at least three HDV genotypes: I, II, and III. HDV isolates of Genotype I have been reported in every part of the world, and the pathogenesis of Genotype I infections varies from fulminant hepatitis to asymptomatic chronic liver disease. The milder HDV II genotype is found primarily in Asia, including Japan, Taiwan, and Russia. Some sequences from Taiwan and the Okinawa islands have been assigned to a subtype of Genotype II, called Genotype IIB. HDV genotype III has been isolated only in northern South America (Peru, Venezuela, and Columbia) and is associated with severe acute hepatitis. Furthermore, HDV genotype I is the only genotype found in some locations, including Europe and North America. Multiple genotypes have been detected in Africa and in Asia. Mixed infections of genotypes I and II or II and IIb have been reported in Taiwan. Furthermore, 15 of 22 recently characterized African sequences formed new lineages and the other 7 are scattered within genotype I. Therefore, recent work has indicated that the current classification of HDV into only three genotypes is incomplete.
Molecular Biology
HDV consists of a single stranded, negative sense, circular RNA virus, with an envelope made up of HBAg. Virions are 35-43 nm and are roughly spherical, with no distinct nucleocapsid structure. The nucleocapsid is made up of 60 large and small delta antigens. These are the only proteins encoded by HDV. HDV relies on host cell machinery for replication, and the viral genome (and antigenome) serves as ribozymes for self-ligation and cleavage. Viral replication occurs in the nucleus of primary hepatocytes using a double-rolling circle mechanism. New virions can be assembled only in the presence of hepatitis B virus. The stages of the viral life cycle, including replication, assembly, and transport, depend on the ratio of small to large delta antigen.