Analysis of the full-length genome of genotype 4 hepatitis E virus isolates from patients with fulminant or acute self-limited hepatitis E

• Published in: Journal of medical virology Vol. 78; no. 4; pp. 476 - 484
• Main Authors: Inoue, Jun, Nishizawa, Tsutomu, Takahashi, Masaharu, Aikawa, Tatsuya, Mizuo, Hitoshi, Suzuki, Kazuyuki, Shimosegawa, Tooru, Okamoto, Hiroaki
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2006; Wiley-Liss
• Subjects: Acute Disease; Aged; Base Sequence; Biological and medical sciences; full-length genome; fulminant hepatitis; Fundamental and applied biological sciences. Psychology; Genome, Viral; Genotype; Hepatitis E - physiopathology; Hepatitis E - virology; Hepatitis E virus; Hepatitis E virus - classification; Hepatitis E virus - genetics; Hepatitis E virus - isolation & purification; Hepatitis E virus - pathogenicity; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Molecular Sequence Data; Mutation; Phylogeny; Sequence Analysis, DNA; Severity of Illness Index; silent mutation; Viral diseases; Viral hepatitis; Virology; Human; full-length genome; silent mutation; Acute; Hepatic disease; Genotype; fulminant hepatitis; Hepatitis E virus; Infection; Virus; Calicivirus; Caliciviridae; Viral disease; Digestive diseases; Isolate; Mutation; Genome; Viral hepatitis E
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.20565

It was suggested that hepatitis E virus (HEV) genotype 4 is associated more closely with the severity of hepatitis E than genotype 3, although the virological basis remains unknown. The aim of this study was to examine whether genomic differences among genotype 4 HEVs are responsible for the development of fulminant hepatitis. Full‐length sequences of genotype 4 HEVs from three patients with fulminant hepatitis and six patients with acute self‐limited hepatitis were determined. The sequences were analyzed with those of 13 genotype 4 HEV isolates whose entire nucleotide sequence is known. Analysis of 22 full‐length sequences (fulminant hepatitis, 5; acute hepatitis, 17) revealed that C at nt 1816 and U at nt 3148 (U3148), both of which do not change the amino acid sequences, were significantly associated with fulminant hepatitis (P = 0.0489, respectively). When partial nucleotide sequences containing nt 1816 or nt 3148 were determined in 16 additional HEV isolates of genotype 4, a closer association between U3148 and fulminant hepatitis (P = 0.0018) was observed. The comparison of 86 HEV isolates of all four genotypes showed that U3148 had a stronger association with fulminant hepatitis than other nucleotides at nt 3148 (P = 0.0006). Patients infected with HEV with U3148 had a significantly lower value of the lowest prothrombin activity (P = 0.0293). Nt 3148 is located within the RNA helicase domain, and 22‐nt sequence including nt 3148 was well conserved among all genotypes. A silent substitution of U3148 in HEV may be associated with the development of fulminant hepatitis. Further studies are needed to clarify the underlying mechanism. J. Med. Virol. 78:476–484, 2006. © 2006 Wiley‐Liss, Inc.