Hepatitis D virus (HDV), also known as Delta virus, is an RNA virus that infects hepatocytes and causes hepatitis D. HDV can infect only individuals who have already infected by Hepatitis B virus. More than 15 million people all over the world were co-injected by HDV and HBV. Three genotypes (I–III) were identified. Genotype I was isolated in Europe, North America and part of Asia. Genotype II was isolated in Japan, Taiwan and part of Russia, and some genomes which are found in Asia-Pacific areas are difficult to be typed and are placed into genotype II as well. Genotype III was isolated only in South America (Colombia, Peru, and Venezuela).
Fig.1 Structure of HDV virion.
HDV is a small spherical RNA virus with a diameter of 36nm. It is an enveloped virus. Three kinds of HDV envelope protein (small, medium and large HDV antigens) and host lipids were identified from the outer envelope of HDV. The HDV capsid is covered by the envelope and consists of about 200 HDV antigen proteins (HDAg). The center region of HDAg was found to bind to the viral genome. HDV genome is a single-stranded RNA consists of about 1700 nucleotides, which makes HDV the smallest virus known to infect animals. This RNA is a negative sense, enveloped, closed circle RNA with high GC content, which is quite unique for animal virus.
HDV achieves the entry into hepatocytes through the NTCP bile transporter as well as the HBV. It recognizes the receptor with the association of the N-terminal domain of the large HBV antigen (HBsAg). After the entrance, HDV particles were uncoated to release the nucleocapsid to the nucleus through HDAg signaling. The virus uses the cellular RNA polymerases for HDA replication. Its RNA genome will be treated as double-stranded DNA by the RNA polymerases for replication due to the folded rod-like structure it is in. Three forms of RNA are produced: circular genomic RNA, circular complementary antigenomic RNA, and a linear polyadenylated antigenomic RNA. The linear polyadenylated antigenomic RNA contains the open reading frame for the HDAg.
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