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Hepatitis D

Hepatitis D is a highly defective virus since it cannot produce infective virions without the help of a co-infecting helper virus. This helper virus is hepatitis B virus that supplies the HBsAg surface protein. In budding out of the cell, HDV acquires a membrane containing HBsAg. 
HDV is similar to a plant viroid in that it has a small circular RNA genome (1,700 bases) but unlike the plant viroids, the RNA encodes a protein called the delta antigen. This complexes with the RNA. The RNA is single stranded negative sense and is a covalently closed circle. Because of a large amount of base pairing, the RNA takes on a rod-like structure .
HDV can only form an infectious particle if the cell in which it replicates is co-infected with HBV since the latter provides the surface HBsAg which is required for reinfection of another cell. The HBsAg of HDV binds to the same surface receptor as HBV and the virus fuses with the cell membrane. The tropism of HDV is therefore the same as HBV. The RNA genome is coated with delta antigen, the only protein encoded by the RNA. The delta antigen, which is exposed when the envelope is lost, has a nuclear localization signal that targets the genome to the nucleus. Here the genome is copied by host cell RNA polymerase II, the enzyme that normally makes mRNA.

 RNA polymerase II is used by some other viruses to copy their genomes, for example, the retroviruses, but in that case the polymerase copies DNA to RNA (which is the normal function of the enzyme in the uninfected cell). In HDV replication, the polymerase is copying RNA to RNA. 
The negative sense genomic RNA is copied to a positive strand that is also circular. The genomic RNA can also be transcribed into a linear 5’ capped and 3’ polyadenylated mRNA which is smaller than the genomic RNA and contains the small open reading frame from which the delta antigen is translated; or it can be generated from the circular positive sense genomic-sized RNA by an autocatalytic process that cleaves the RNA. Thus, the RNA is acting as a ribozyme, that is a catalytic RNA .

Delta antigen, translated from the mRNA has two forms that differ in size by 19 amino acids (195 compared to 214 residues). The formation of the large delta antigen happens by a rather strange mechanism in which a host cell enzyme called double stranded RNA-activated adenosine deaminase converts a UAG (stop) codon into a UGG that allows translation to proceed to the next stop codon. 
The small delta antigen is involved in the replication of the genome but the larger form suppresses replication. This leads to the promotion of viral particle assembly.

tags:hepatitis D,virus is hepatitis B virus that supplies the HBsAg ,Delta antigen,


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