Abstract
Background
In our recent study of the full-length hepatitis A virus (HAV) genome from some patients with fulminant hepatitis and acute hepatitis, possible associations were suggested between the severity of hepatitis A and the amino acid substitutions in the nonstructural protein 2B. We therefore analyzed HAV 2B from many patients with various clinical disease severities.
Methods
Serum samples from 30 Japanese patients with sporadic hepatitis A from five widely separated regions of Japan, comprising nine patients with fulminant hepatitis (FH), six with severe acute hepatitis (AHs), and 15 with acute hepatitis (AH), were examined for HAV RNA. The entire sequences of HAV 2B were analyzed.
Results
Compared with the sequence of the wild-type HAV strain GBM, nucleotide sequences of 2B had homology of 94.5 ± 1.0% in FH, 95.2 ± 1.2% in AHs, and 95.1 ± 1.8% in AH. Deduced amino acid sequences had homology of 97.5 ± 2.1% in FH, 97.9 ± 2.4% in AHs, and 98.5 ± 1.3% in AH. Differences were not statistically significant among the three groups. The average number of amino acid mutations between amino acids 100 and 200 was 5.0 ± 5.2 per case in FH, 4.0 ± 6.0 in AHs, and 1.9 ± 2.9 in AH. The differences between FH and AH, AHs and AH, and between severe cases (FH and AHs) and nonsevere cases (AH) were not statistically significant (P = 0.13, P = 0.45, and P = 0.10, respectively).
Conclusions
There were no obvious differences in the sequences among FH, AHs, and AH throughout the 2B region, but there seemed to be more mutations in the strains obtained from FH and AHs patients than in those obtained from AH patients in the central part of HAV 2B.
Similar content being viewed by others
References
Y Takahashi K Okuda (1993) ArticleTitleFulminant and subfulminant hepatitis in Japan Indian J Gastroenterol 12 19–21 Occurrence Handle8005630
K Fujiwara T Ehata O Yokosuka F Imazeki M Ohto Y Ohtake et al. (1995) ArticleTitleThe recent increase of severe type A hepatitis in Chiba area Int Hepatol Commun 3 S37 Occurrence Handle10.1016/0928-4346(95)90299-M
K Fujiwara O Yokosuka T Ehata F Imazeki H Saisho (2000) ArticleTitlePCR-SSCP analysis of 5′ nontranslated region of hepatitis A viral RNA: comparison with clinicopathological features of hepatitis A Dig Dis Sci 45 2422–7 Occurrence Handle10.1023/A:1005607512633 Occurrence Handle1:CAS:528:DC%2BD3MXisVynt7w%3D Occurrence Handle11258569
JI Cohen JR Ticehurst RH Purcell A Buckler-White BM Baroudy (1987) ArticleTitleComplete nucleotide sequence of wild-type hepatitis A virus: comparison with different strains of hepatitis A virus and other picorna viruses J Virol 61 50–9 Occurrence Handle1:CAS:528:DyaL2sXpslSnsw%3D%3D Occurrence Handle3023706
K Fujiwara O Yokosuka T Ehata F Imazeki H Saisho M Miki et al. (1997) ArticleTitleFrequent detection of hepatitis A viral RNA in serum during the early convalescent phase of acute hepatitis A Hepatology 26 1634–9 Occurrence Handle10.1002/hep.510260636 Occurrence Handle1:STN:280:DyaK1c%2FlvVKiug%3D%3D Occurrence Handle9398009
K Fujiwara O Yokosuka K Fukai F Imazeki H Saisho M Omata (2001) ArticleTitleAnalysis of full-length hepatitis A virus genome in sera from patients with fulminant and self-limited acute type A hepatitis J Hepatol 35 112–9 Occurrence Handle10.1016/S0168-8278(01)00074-5 Occurrence Handle1:CAS:528:DC%2BD3MXmtVylsLY%3D Occurrence Handle11495028
K Fujiwara O Yokosuka T Ehata H Saisho N Saotome K Suzuki et al. (2002) ArticleTitleAssociation between severity of type A hepatitis and nucleotide variations in the 5′ nontranslated region of hepatitis A virus RNA: strains from fulminant hepatitis have fewer nucleotide substitutions Gut 51 82–8 Occurrence Handle10.1136/gut.51.1.82 Occurrence Handle1:CAS:528:DC%2BD38XlslOis78%3D Occurrence Handle12077097
M Jecht C Probst V Gauss-Muller (1998) ArticleTitleMembrane permeability induced by hepatitis A virus proteins 2B and 2BC and proteolytic processing of HAV 2BC Virology 252 218–27 Occurrence Handle10.1006/viro.1998.9451 Occurrence Handle1:CAS:528:DyaK1cXotFSiurw%3D Occurrence Handle9875331
Y Takahashi M Shimizu (1991) ArticleTitleAetiology and prognosis of fulminant viral hepatitis in Japan: a multicentre study. The Study Group of Fulminant Hepatitis J Gastroenterol Hepatol 6 159–64 Occurrence Handle10.1111/j.1440-1746.1991.tb01458.x Occurrence Handle1:STN:280:DyaK38%2FgtlCrtA%3D%3D Occurrence Handle1912424
H Okamoto S Okada Y Sugiyama T Tanaka Y Sugai Y Akahane et al. (1990) ArticleTitleDetection of hepatitis C virus RNA by a two-step polymerase chain reaction with two pairs of primers deduced from the 5′-noncoding region Jpn J Exp Med 60 215–22 Occurrence Handle1:STN:280:DyaK3M7lsFahuw%3D%3D Occurrence Handle1963453
K Fujiwara O Yokosuka F Imazeki H Saisho N Saotome K Suzuki et al. (2003) ArticleTitleAnalysis of the genotype-determining region of hepatitis A viral RNA in relation to disease severities Hepatol Res 25 124–34 Occurrence Handle10.1016/S1386-6346(02)00245-0 Occurrence Handle1:CAS:528:DC%2BD3sXitV2nu78%3D Occurrence Handle12644048
J Graff A Normann SM Feinstone B Flehmig (1994) ArticleTitleNucleotide sequence of wild type hepatitis A virus GBM in comparison with two cell culture-adapted variants J Virol 68 548–54 Occurrence Handle1:CAS:528:DyaK2cXhsFGhtL0%3D Occurrence Handle8254770
H Muraoka (1990) ArticleTitleClinical and epidemiological study on factors of serious development of viral hepatitis type A Nippon Shokakibyo Gakkai Zasshi 87 1383–91 Occurrence Handle1:STN:280:DyaK3M%2FhtlWhtA%3D%3D Occurrence Handle2214263
IR Willner MD Uhl SC Howard EQ Williams CA Riely B Waters (1998) ArticleTitleSerious hepatitis A: an analysis of patients hospitalized during an urban epidemic in the United States Ann Intern Med 128 111–4 Occurrence Handle1:STN:280:DyaK1c%2FosFygtA%3D%3D Occurrence Handle9441570
S Vento T Garofano C Renzini F Cainelli F Casali G Ghironzi et al. (1998) ArticleTitleFulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C N Engl J Med 338 286–90 Occurrence Handle10.1056/NEJM199801293380503 Occurrence Handle1:STN:280:DyaK1c%2Fpt1SksQ%3D%3D Occurrence Handle9445408
R Gosert D Egger K Bienz (2000) ArticleTitleA cytopathic and a cell culture adapted hepatitis A virus strain differ in cell killing but not in intracellular membrane rearrangement Virology 266 157–69 Occurrence Handle10.1006/viro.1999.0070 Occurrence Handle1:CAS:528:DyaK1MXotFGktrw%3D Occurrence Handle10612670
SU Emerson C McRill B Rosenblum SM Feinstone RH Purcell (1991) ArticleTitleMutations responsible for adaptation of hepatitis A virus to efficient growth in cell culture J Virol 65 4882–6 Occurrence Handle1:CAS:528:DyaK3MXlsFaisLo%3D Occurrence Handle1651411
SU Emerson Y-K Huang C McRill M Lewis RH Purcell (1992) ArticleTitleMutations in both the 2B and 2C genes of hepatitis A virus are involved in adaptation to growth in cell culture J Virol 66 650–4 Occurrence Handle1:CAS:528:DyaK38XhtVSntbY%3D Occurrence Handle1309907
V Tedeschi RH Purcell SU Emerson (1993) ArticleTitlePartial characterization of hepatitis A viruses from three intermediate passage levels of a series resulting in adaptation to growth in cell culture and attenuation of virulence J Med Virol 39 16–22 Occurrence Handle10.1002/jmv.1890390105 Occurrence Handle1:STN:280:DyaK3s7jvFOqsA%3D%3D Occurrence Handle8380839
AW Funkhouser RH Purcell E D'Hondt SU Emerson (1994) ArticleTitleAttenuated hepatitis A virus: genetic determinants of adaptation to growth in MRC-5 cells J Virol 68 148–57 Occurrence Handle1:CAS:528:DyaK2cXht12gtrs%3D Occurrence Handle8254724
J Graff C Kasang A Normann M Pfisterer-Hunt SM Feinstone B Flehmig (1994) ArticleTitleMutational events in consecutive passages of hepatitis A virus strain GBM during cell culture adaptation Virology 204 60–8 Occurrence Handle10.1006/viro.1994.1510 Occurrence Handle1:CAS:528:DyaK2cXlslKnu78%3D Occurrence Handle8091685
F Beneduce G Psani M Divizia A Pana G Morace (1995) ArticleTitleComplete nucleotide sequence of a cytopathic hepatitis A virus strain isolated in Italy Virus Res 36 299–309 Occurrence Handle10.1016/0168-1702(95)00009-F Occurrence Handle1:CAS:528:DyaK2MXlsFKjtro%3D Occurrence Handle7653108
H Zhang S-F Chao LH Ping K Grace B Clarke SM Lemon (1995) ArticleTitleAn infectious cDNA clone of a cytopathic hepatitis A virus: genomic regions associated with rapid replication and cytopathic effect Virology 212 686–97 Occurrence Handle10.1006/viro.1995.1526 Occurrence Handle1:CAS:528:DyaK2MXosFWgtL8%3D Occurrence Handle7571438
G Raychaudhuri S Govindarajan M Shapiro RH Purcell SU Emerson (1998) ArticleTitleUtilization of chimeras between human (HM-175) and simian (AGM-27) strains of hepatitis A virus to study the molecular basis of virulence J Virol 72 7467–75 Occurrence Handle1:CAS:528:DyaK1cXlsVSmsLo%3D Occurrence Handle9696843
K Brack W Frings A Dotzauer A Vallbracht (1998) ArticleTitleA cytopathic, apoptosis-inducing variant of hepatitis A virus J Virol 72 3370–6 Occurrence Handle1:CAS:528:DyaK1cXhvVOhtLk%3D Occurrence Handle9525664
Fujiwara K, Yokosuka O, Imazeki F, Miki M, Suzuki K, Okita K, et al. Genetic analysis of hepatitis A virus protein 2C in sera from patients with fulminant and self-limited hepatitis A. Hepatogastroenterology (in press)
Author information
Authors and Affiliations
Additional information
An erratum to this article can be found online at http://dx.doi.org/10.1007/s00535-007-2154-5.
Rights and permissions
About this article
Cite this article
Fujiwara, K., Yokosuka, O., Imazeki, F. et al. Analysis of hepatitis A virus protein 2B in sera of hepatitis A of various severities. J Gastroenterol 42, 560–566 (2007). https://doi.org/10.1007/s00535-007-2039-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00535-007-2039-7