Nucleotide sequence of an infectious molecularly cloned genome of ground squirrel hepatitis virus

Abstract

We have determined the complete nucleotide sequence of an infectious cloned genome of ground squirrel hepatitis virus (GSHV), a nonpathogenic member of the hepadnavirus group. The genome is 3,311 base pairs long and contains the major open reading frames described for the related human and woodchuck hepatitis B viruses (HBV and WHV, respectively). These reading frames include genes for the major structural proteins (the surface and core antigens), unassigned open reading frames (A and B), the longer of which is presumed to encode the viral DNA polymerase, and an open reading frame preceding and continuous with the surface antigen gene. The arrangement of these open reading frames is similar to that encountered in the genomes of HBV and WHV: all of the reading frames are encoded on the same strand, they are positioned in the same fashion with respect to each other, and a large portion (at least 51%) of the genome can be translated in two reading frames. Comparisons of the predicted translational products of the three mammalian hepadnaviruses reveal 78% amino acid homology between the proteins of GSHV and WHV and 43% homology between those of GSHV and HBV. In addition, a perfect direct repeat of 10 to 11 base pairs, separated by ca. 46 to 223 base pairs, is present in the three mammalian viruses and in duck hepatitis B virus; the position of the repeats near the 5' termini of the two strands of virion DNA suggests a role in viral replication.

The X protein of the hepatitis B virus acts as a transcription factor when targeted to its responsive element.

“…The strong repression of the enhancer activity of XRE obtained under these conditions suggests that the truncated C/EBP (the DB gene) is efficiently expressed in transfected cells and that the protein product is translocated to the nuclei and binds to XRE. The possibility that this protein binds to additional sites within the reporter plasmid was not excluded in our experiments, but this should not Seeger et al, 1984) and woodchuck hepatitis virus (WHBV, Kodama et al, 1985). Identical amino acids are boxed.…”

Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region

“…This affects the ORF for HBcAg (cD153 and cR154), but not hepatitis B e antigen (HBeAg) (not shown), because this length polymorphism is located immediately carboxyterminal of the HBeAg processing site. None of the other human or ape HBV genotypes have this 2 amino acid insertion, but remarkably, there is a 5 amino acid insertion present at the same position in rodent hepadnaviruses (woodchuck hepatitis virus, 59 Arctic ground squirrel hepatitis virus, 60 and ground squirrel hepatitis virus 61 ; not shown). Because the efficiency of the backwards scanning mechanism depends on the distance between the 3Ј end of the core ORF and initiation of the polymerase ORF 43 (143 nucleotides for genotype B-G, 149 for genotype A, 158 for rodent hepatitis viruses), these length polymorphisms might help control the translation of the polymerase protein from the pregenomic mRNA in a genotype-dependent manner.…”

Signals for ribosomal frameshifting in the rous sarcoma virus gag-pol region

“…The original truncation plasmids were cleaved with Pvul (which cuts in the vector) and Pstl and were ligated to a complementary Pvul-Pstl fragment from an SP6 promoter-containing plasmid (Melton et al, 1984) carrying the complete GS-sAg gene. The Pstl site in GS-sAg corresponds to position 1518 in Seeger et al (1984). SP6 transcription reactions, rabbit reticulocyte translations.…”