The complete genomic sequence of hepatitis delta virus genotype IIb prevalent in Okinawa, Japan

Abstract

The Miyako Islands, located in the southernmost part of Japan, have been reported to be endemic for hepatitis delta virus (HDV). The majority of HDV patients in this area exhibit a relatively mild course of infection that evolves into a quiescent cirrhotic condition. The entire nucleotide sequence of the Miyako isolate (L215) of HDV obtained from a cirrhotic patient infected with HDV was determined. This isolate, L215, comprises 1682 nt and encodes 213 aa of the hepatitis delta antigen. Phylogenetic analysis showed that L215 is closely related to the Taiwanese genotype IIb HDV isolate. In addition, the predicted folding structure of the antigenomic RNA substrate was different from those of the published genotype II sequences.Hepatitis delta virus (HDV) is a unique, viroid-like human pathogen that needs to be associated with hepatitis B virus infection (Monjardino, 1996). It was first detected in the liver cell nuclei of patients with hepatitis B surface antigen (HBsAg)-positive chronic liver disease (Rizzetto et al., 1977). HDV has a single-stranded, negative-sense, circular RNA genome of 1?7 kb in length (Wang et al., 1986(Wang et al., , 1987Makino et al., 1987;Saldanha et al., 1990;Imazeki et al., 1991;Casey et al., 1993;Lee et al., 1996;Wu et al., 1998). The RNA genome encodes two proteins, 24 and 27 kDa, referred to as the small hepatitis delta antigen (S-HDAg) and the large hepatitis delta antigen (L-HDAg), respectively (Bonino et al., 1986;Bergmann & Gerin, 1986). S-and L-HDAg share the same initiation codon but use different termination codons (Wang et al., 1986;Weiner et al., 1988). Each HDAg is translated from a distinct mRNA species, arising from a unique RNA-editing event. The two forms of HDAg have distinct and opposing functions: S-HDAg is required for HDV replication, whereas L-HDAg inhibits HDV replication and is required for virion formation (Gerin et al., 2001).Based on geographical origin and genomic divergence, HDV strains are divided into at least three genotypes: I, II and III (Casey et al., 1993;Lai, 1995). Recently, Wu et al. (1998) reported a novel strain of genotype II in Taiwan and proposed genotypes IIa and IIb. The Miyako Islands, which are located in the southernmost part of Japan, about 390 km east of Taiwan, are one of the areas in Japan that is endemic for HDV (Sakugawa et al., 1995(Sakugawa et al., , 1997a(Sakugawa et al., , b, 1999Nakasone et al., 1998;Arakawa et al., 2000). The majority of patients with chronic HDV-related liver disease in the Miyako Islands exhibit a relatively mild course of infection that evolves to a quiescent cirrhotic condition (Sakugawa et al., 1997a). Sakugawa et al. (1999) sequenced the 645 nt of HDAg (position 940-1584; numbering according to Wang et al., 1987) of six strains of genotype II, collected from patients with HDV-related chronic liver disease in the Miyako Islands, and reported the presence of genotype IIb. However, the entire genome sequence of the Miyako isolate has not been reported. Hence, we describe the entire nucleotide sequence o...

Genetic diversity and worldwide distribution of the deltavirus genus: A study of 2,152 clinical strains

“…). HDV‐4a (formerly HDV‐IIb) and HDV‐4b (formerly HDV‐IIb‐M) originated from Taiwan and Japan, respectively (Fig. ; http://onlinelibrary.wiley.com/doi/10.1002/hep.29574/suppinfo).…”

Quantitation of the Level of Hepatitis Delta Virus RNA in Serum, by Real‐Time Polymerase Chain Reaction—and Its Possible Correlation with the Clinical Stage of Liver Disease

“…In the Miyako Islands, HBV ge-notype B and HDV genotype II are prevalent [28,29]. These genotypes are reported to be linked to liver disease that is milder than that associated with other genotypes [30].…”

Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD

“…This size range includes hepatitis δ, a satellite virus with a genome of 1,682 nt (Ma et al 2003), circoviruses found in both plants and animals (16-22 nm, ∼2,500 nt), and circovirus-like Anneloviruses of primates. The latter are commensal and, like TSE agents, can also persist in myeloid cells.…”