The RNAs of hepatitis delta virus are copied by RNA polymerase II in nuclear homogenates

Abstract

Human hepatitis delta virus has a single-stranded circular RNA genome that replicates by RNA-directed RNA synthesis. The virus encodes only a single protein, the delta antigen, which both is small (22 kDa) and lacks sequence homology to known RNA polymerases, suggesting that the virus employs a cellular polymerase for replication. Consistent with this suggestion, we have used homogenized nuclei from a human hepatoma cell line, HepG2, to demonstrate RNA-directed RNA synthesis from both genomic hepatitis delta virus RNA and its complement, the antigenomic RNA. RNA polymerase II was responsible for this transcription because the reaction was inhibited both by low doses of alpha-amanitin and by a monoclonal antibody specific for polymerase II. In addition, it was found that the majority of the RNA products were processed, presumably by self-cleavage and self-ligation, to produce covalently closed circular molecules.

Cell‐to‐cell movement of potato spindle tuber viroid

“…In this regard, it is of particular interest to note that hepatitis delta virus (HDV) RNA is similar to viroid RNA by being circular, single-stranded and assuming an unbranched rod-like structure (Kos et aL, 1986;Wang et aL, 1986). Replication of HDV RNA is carried out by the host RNA polymerase II and involves no DNA intermediate (Fu and Taylor, 1993;Macnaughton et al, 1991). However, either linearized or recircularized monomeric HDV cDNA can initiate HDV RNA transcription and replication, and this is a function of an endogenous promoter present in the cDNA (Macnaughton et al, 1993;Tai et aL, 1993).…”

Master of Disguise: Hepatitis Delta Virus Packaging and Spread Facilitated by Diverse Viral Envelope Proteins

“…(2) This delta antigen was later formally recognized as the hepatitis delta virus, and by 1993, its ability to replicate utilizing host RNA polymerase II without HBV's assistance was demonstrated. (3) Thus, using HBV glycoproteins, HDV can form an envelope encapsidating its negative sense, single-stranded circular RNA bound to HDAg. In this way, HDV can successfully enter, replicate, and exit hepatocytes expressing sodium-taurocholate cotransporting polypeptide, the HBV entry receptor.…”

Hepatitis Delta – 2019. Part I: the Aetiology, Epidemiology, Features of the Clinical Course and Outcomes

“…Лишь в 1993 г. были опубликованы результаты важнейшего исследования T.B. Fu и J. Taylor [11], позволившие расширить знания о роли HBV и гепатоцитов в репликации HDV. Транскрипция геномной и антигеномной вирусной РНК осуществляется при участии РНК-полимеразы двух гепатоцитов.…”

“…Предполагалось, что особая форма вирусной РНК может распознаваться РНК-полимеразой-2 как стандартная двухцепочечная ДНК. Конечный итог репликации -преобразование геномной и антигеномной РНК, катализированной рибозимом, с разъединением продукта транскрипции (геномная -антигеномная РНК) в форму циркулярной РНК вируса HDV [11][12][13][14]. Таким образом, HDV -дефектный РНК-вирус, требующий HBsAg от HBV для сборки вириона, его высвобождения и передачи.…”