Delta virus

The ribozymes were widely modified and can be further subdivided according to their structural features in group I ribozymes, hammerhaed ribozymes, hairpin ribozymes, ribonucelase P (RNase P), and hepatitis delta virus ribozymes. 

IFN-Based Treatment of Hepatitis D/Delta Virus Infection.226... 

Worldwide, 15 million HBsAg carriers are also infected with hepatitis D/delta virus (HDV) (Gaeta et al. 2000). This situation represents a major therapentic challenge, as most of these patients have advanced liver disease, inclnding cirrhosis in 60-70% of cases, and hepatocellular carcinoma (Fattovich et al. 2000 Saracco et al. 1987). No specific HDV inhibitors have been developed, and IFN-a-based treatment is more difficnlt in HBV-HDV infection than in HBV monoinfection. HDV RNA levels in sernm can be nsed to monitor treatment efficacy. The endpoint of therapy is HDV RNA clearance and ALT normalization, and this is sometimes achieved after the end of treatment. A snstained response can lead to HBsAg clearance from serum. 

Fattovich G, Giustina G, Christensen E, Pantalena M, Zagni I, Realdi G, Schalm SW (2000) Influence of hepatitis delta virus infection on morbidity and mortahty in compensated cirrhosis type B. Gut 46 420 26... 

Saracco G, Rosina F, Brunetto MR, Amoroso P, Caredda F, Farci P, Piantino P, Bonino F, Rizzedo M (1987) Rapidly progressive HBsAg-positive hepatitis in Italy. The role of hepatitis delta virus infection. J Hepatol 5 274-281... 

In mid-1997 an international conference took place in Santa Cruz, USA, in which, for the first time, the exclusive topic was structural aspects of RNA molecules. A report covering this meeting contains an impressive graphic which shows the RNA structures, RNA/DNA complexes, and RNA/protein complexes contained in the brookhaven database as a function of the year of their publication [29]. Between 1988 and 1993 there were just 20. However, in 1996 alone no less than 41 structures appeared. These new dimensions were headed by the crystal structural elucidation of the first larger RNA molecule since the first crystal structure of tRNA in 1973 [30], the 48 nucleotide long hammerhead ribo-zyme (HHR) [31-33]. This landmark achievement was followed by a crystal structure analysis of the P4-P6-domain of a group I intron [34-36] and, more recently, a crystal structure of the hepatitis delta virus ribozyme [37]. 

The hepatitis delta virus (HDV) ribozyme is part of the circular single stranded RNA genome of the hepatitis delta virus which consists of a total of 1700 nucleotides. The HDV ribozyme is required for the processing of multimers of the genomic linear RNA transcripts to unit length by catalyzing a transesterification reaction that results in self cleavage [23]. 

Fig. 3. The hepatitis delta virus ribozyme. A Secondary structure of the genomic HDV ribo-zyme RNA used for the determination of the crystal structure [37]. The color code is reflected In the three dimensional structure B of this ribozyme. PI to P4 indicate the base-paired regions. Nucleotides in small letters indicate the U1 A binding site that was engineered into the ribozyme without affecting the overall tertiary structure. The yellow region indicates close contacts between the RNA and the U1 A protein...

HDV ribozymes are derived from the genomic and the antigenomic RNAs of hepatitis delta virus [99-102]. Studies by three groups have revolutionized our understanding of the mechanism of HDV ribozyme-catalyzed reactions [28, 103, 104]. They demonstrated recently that an intramolecular functional group, namely N3 at Gye in the antigenomic HDV ribozyme and N3 at C75 in the genomic HDV ribozyme, can, in fact, act as a true catalyst. However,... 

Isambert, H. and Siggia, E. D. (2000). Modeling RNA folding paths with pseudoknots application to hepatitis delta virus ribozyme. Proc. Natl. Acad. Sci. USA 97, 6515-6520. 

Immunization against infection caused by all known subtypes of hepatitis B virus. As hepatitis D (caused by the delta virus) does not occur in the absence of hepatitis B infection, because risk factors tor hepatitis C are similar to those tor hepatitis B, immunization with hepatitis B vaccine is recommended for individuals with chronic hepatitis C. 

Perrotta, A.T. and Been, M.D. (1993) Assessment of disparate structural features in three models of the hepatitis delta virus ribozyme. Nucleic Acids Res., 21, 3959-3965. 

Fig. 1.1.1. Example of an RNA sequence that can adopt two different defined folds, each associated with a specific biological activity (HDV hepatitis delta virus).

The RNA oligomers studied by these authors [115, 116] are several evolved sequences (hepatitis delta virus), synthetic polymers (poly-U), and various random RNA sequences. The random sequences are obtained from the HDV sequence by a permutation of the nucleotides in which base composition is fixed [115, 116]. The lengths of all RNA oligonucleotide fragments are 85 nucleotides [115, 116],... 

The hepatitis D virus, also known as the Delta virus, is replication defective in humans it can only replicate in the presence of HBV, and is acquired in the same way. Infection may occur at the same time as the hepatitis B infection (co-infection) or an individual infected with hepatitis B may acquire hepatitis D at a later date (superinfection). The combination of hepatitis B with hepatitis D significantly increases the risk of progression to chronic hepatitis and cirrhosis. 

Shih IH, Been MD. Catalytic strategies of the hepatitis delta virus ribozymes. Annu. Rev. Biochem. 2002 71 887—917. 

Evidence for Acid/Base Catalysis in the Hepatitis Delta Virus Ribozyme Active Site... 

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