An in situ hybridization, molecular biological and immunohistochemical study of hepatitis delta virus in woodchucks

✍ Scribed by Spyros Dourakis; Peter Karayiannis; Robert Goldin; Michael Taylor; John Monjardino; Howard C. Thomas

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 612 KB
• Volume: 14
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840140321

✦ Synopsis

The presence of hepatitis delta virus genomic RNA and hepatitis delta antigen was investigated in woodchuck liver and extrahepatic tissues by in situ hybridization using synthetic radiolabeled probes, Northern-blot analysis and immunohistochemical staining for hepatitis delta antigen. Hepatitis D virus RNA and hepatitis delta antigen were detected in the nuclei of infected hepatocytes but in none of the other tissues examined. Northern-blot analysis of total cell RNA confirmed these findings and revealed a series of hepatitis D virus transcripts, including full-length genomic RNA and dimers and trimers of hepatitis D virus RNA that may represent replicative intermediates. Use of single-stranded probes showed genome-size monomers and dimers to be both of genomic and antigenomic polarity, although dimers were found to be predominantly antigenomic. These findings document the strict hepatotropism of hepatitis D virus and support the rolling-circle model of genome replication for this unique, defective RNA virus. (HFZATOLOGY 1991;14:534-539.)

Hepatitis delta virus (HDV) is a 36-nm defective RNA virus that requires the presence of either human or woodchuck hepadnavirus for infection and propagation. The virus particle contains a circular, single-stranded RNA genome of about 1,700 nucleotides and a capsid that consists of delta antigen, which in turn is surrounded by HBsAg. The structure and properties of the genome (autocleavage, self-ligation) and the proposed mechanism for its replication (rolling circle) are similar to those described for the RNAs of the plant pathogens, the viroids (1-4). Although HDV's dependence on hepadnavirus infection is not fully understood, recent work suggests that the helper function of the latter may be limited to supplying the envelope to the hepatitis D viroid (5). Recent reports have suggested that hepadnaviruses and HDV may differ in tissue tropism; these