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Hepatitis A

Hepatitis A virus

I. Organism Information

A. Taxonomy Information
  1. Species:
    1. Hepatitis A virus :
      1. GenBank Taxonomy No.: 208726
      2. Description: Human hepatitis A virus (HAV) belongs to the family Picornaviridae and is the unique member of the genus Hepatovirus. HAV is a major cause of acute hepatitis (AH) worldwide that sometimes leads to fulminant hepatic (FH) failure, evolving in most countries on an endemo-epidemic mode. However, in some countries, notably in Europe, hygienic improvement led to a fall in HAV seroprevalence during last decades exposing populations to a risk of HAV outbreaks (Mackiewicz et al., 2005). Only one serotype of HAV has been identified and a single infection confers lifelong immunity. However, genetic heterogeneity between HAV isolates from different parts of the world has enabled the classification of HAV strains into seven different genotypes, designated I to VII. Four of these have been associated with human disease, I, II, III, and VII. Most human HAV strains belong to genotypes I and III, with 80% of them being genotype I. Genotypes I and III are further divided into subtypes A and B. Genotypes II and VII are represented only by one human strain each, and genotypes IV, V, and VI include strains recovered from simians (Arauz-Ruiz et al., 2001). Genotype IA appears to be the agent responsible for the majority of hepatitis A cases worldwide and has been isolated from all parts of the world. Genotype IB appears to occur in the Mediterranean region, whereas genotype III viruses have been isolated from diverse sources such as Panamanian owl monkeys, drug abusers in Sweden and patients from India and Nepal. Single representatives of genotype II and VII were isolated from individual patients from Sierra Leone and France (Lu et al., 2004). Several studies have indicated that HAV strains in North America mainly belong to subtype IA (Arauz-Ruiz et al., 2001).
      3. Variant(s):
        • Hepatitis A virus (STRAIN HM-175) :
          • GenBank Taxonomy No.: 12098
          • Description: Genotype IB (Apaire-Marchais et al., 1995, Costa-Mattioli et al., 2003). The HM-175 strain was derived from a fecal sample collected in November 1976 from a 35-year old Australian male with serologically confirmed hepatitis A. The term HM175 has subsequently been used to designate strains of HAV which have been recovered from infected nonhuman primates and cell cultures inoculated with the original fecal extract and their progeny (Gust and Feinstone 1988). Attenuated mutants of HM175, CR326, and H2 are the best characterized candidates for live virus vaccines, but variants of strains GBM and MBB and chimeras between simian AGM27 and human HM175 strains also are being evaluated (Hollinger and Emerson, 2001).
        • Hepatitis A virus (STRAIN 18F) :
          • GenBank Taxonomy No.: 12096
          • Parent: Hepatitis A virus
          • Description: Genotype IB (Apaire-Marchais et al., 1995, Costa-Mattioli et al., 2003). HM175/18f virus is one of several cell culture-adapted HM175 variants which were rescued from persistently infected BS-C-1 cells and which have a rapid replication phenotype associated with cytopathic effects (rrlcpe+) in cultured monkey kidney cells. The nucleotide sequences of these viruses demonstrate the presence of numerous mutations from the sequence of the more slowly replicating noncytopathic (rrlcpe-) parent virus. The HM175/18f virus represents an independent isolate of the HM175 strain of HAV (Zhang et al., 1995).
        • Hepatitis A virus (STRAIN CR326) :
          • GenBank Taxonomy No.: 12097
          • Description: Genotype IA (Hollinger and Emerson, 2001, Costa-Mattioli et al., 2003) CR326 was derived from a pool of sera collected from a 9-year old child during a prospective study of the epidemiology and the mode of transmission of viral hepatitis in semi-urban and rural areas of Alajuela, Costa Rica (Gust and Feinstone 1988). Attenuated mutants of HM175, CR326, and H2 are the best characterized candidates for live virus vaccines, but variants of strains GBM and MBB and chimeras between simian AGM27 and human HM175 strains also are being evaluated (Hollinger and Emerson, 2001).
        • Hepatitis A virus (strain GA76) :
          • GenBank Taxonomy No.: 31706
          • Description: Genotype IIIA (Costa-Mattioli et al., 2001, Costa-Mattioli et al., 2003). Human isolates of hepatitis A (HAV) are a single serotype; however, recent genetic surveys using limited nucleotide sequencing have provided evidence that more than one genotype is responsible for HAV infection in different parts of the world. One of these genotypes was originally isolated from Panamanian owl monkeys (strain PA21), but has subsequently been found associated with human cases of HAV from Sweden in 1979 (H-122) and the United States of America in 1976 (GA76). HAV infected stool specimens from Nepal and northern India during 1989 and 1990 were found to contain virus whose genetic makeup was related to the PA21 and GA76 isolates. This genotype of HAV appears to be circulating in some parts of the world where HAV is hyperendemic, and is a potential cause of hepatitis A infection within a susceptible population (Khanna et al., 1992).
        • Hepatitis A virus (STRAIN LCDC-1) :
          • GenBank Taxonomy No.: 12093
          • Description: Chinese strain of hepatitis A virus (HAV) (Andonov et al., 1989). There is an 18 bp deletion in the capsid protein, VP1 gene, compared to HAV strains HM-175, MBB, and CR-326 (NCBI Entrez).
        • Hepatitis A virus (STRAIN MBB) :
        • Hepatitis A virus isolate CF53/Berne :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: Genotype II (Apaire-Marchais et al., 1995). The CF53/Berne is a cell-adapted isolate of HAV donated to the Berne laboratory. The original virus was derived in 1979 from the stool of a patient in Clermont-Ferrand, France, who had sporadic hepatitis A 3 days after the onset of jaundice. The CF53/Berne isolate sequence was compared to the complete available sequences of four representative HAV genotypes [genotype IA (GBM), genotype IB (HM-175), genotype III (NOR-21), genotype V (AGM27) and genotype VII (SLF88)] and shown to be related closest to the SLF88 strain. This close relationship was maintained when the three major protein-encoding region (P1, P2 and P3) were analyzed separately. Evaluation of the more conserved 5' UTR revealed that the CF53/Berne isolate had over 96% identity to human HAV genotype VII, about 92% identity to the human genotype IA and IB and approximately 83% identity to the simian HAV genotype V sequence (Lu et al., 2004).
        • Hepatitis A virus strain SLF88 :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: Genotype VII (Apaire-Marchais et al., 1995, Ching et al., 2002, Costa-Mattioli et al., 2003). It was previously identified as genotype VII, genotype: IIB (NCBI Entrez). Human HAV genotype VII, designated SLF88 was responsible for two epidemiologically linked fulminant hepatitis A cases and is the only identified strain from Sierra Leone. Within hyper-endemic regions, such as the Amazon basin in South America, most of Africa, the Middle East and Central Asia and the Indian subcontinent, the majority of infections occur during childhood. In these areas, distinct outbreaks occur rarely and clinical disease related to HAV infection is uncommon, as children generally experience asymptomatic infection. SLF88 is the only wild-type virus from this part of Africa for which we have a complete genome sequence (Ching et al., 2002).
        • Hepatitis A virus isolate DL3 :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: Wild-Type Hepatitis A Virus isolate DL3 in China belonged to subgenotype IA (Liu et al., 2003) HAV (DL3) was isolated from a stool specimen collected from hepatitis A patient from Dalian, China. The sequence comparison and phylogenetic analysis revealed that DL3 is most similar to the isolates in Japan, suggesting the epidemiological link of hepatitis A happened in China and Japan (Liu et al., 2003).
        • Hepatitis A virus strain GBM :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: HAV strain GBM was recovered from a human fecal specimen, collected in the preicteric phase of the infection in Germany, and is named GBM wild type (GBM/WT) in this paper. The strain has been adapted for growth in HFS (human lung fibroblast cells) and/or FRhK-4 cells (fetal rhesus monkey kidney-derived cells) with a selection procedure for rapid growth and release of virus into cell culture supernatant. The comparison of the genome between the GBM wild type and HAV wild types HM175 and HAV-LA showed a 92 to 96.3% identity, whereas the identity was 99.3 to 99.6% between the GBM variants. Nucleotide differences between the wild-type and the cell culture-adapted variants, which were identical in both cell culture-adapted GBM variants, were localized in the 5' noncoding region; in 2B, 3B, and 3D; and in the 3' noncoding region (Graff et al., 1994). The alignment of the genome sequence of the GBM wild type with other HAV wild-type sequences has shown a 92% (HM175) to 96.3% (HAV-LA) identity and classifies the GBM strain as subgenotype IA within the seven genotypes of human HAV isolated from different geographical regions. The comparison of the consensus sequence, a 168-nucleotide region encoding the putative VPI-2A junction, shows that wild-type HAV-LA is also a member of subgenotype IA but differs in comparison with the sequence of GBM/WT (Graff et al., 1994).
        • Hepatitis A virus substrain GMB/FRhK :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: Two GBM variants, GBM/HFS and GBM/FRhK, were attained after cell culture propagation. GBM/FRhK was isolated and propagated in FRhK-4 cells and after 63 passages exhibited a strict host range behavior. The two GBM cell culture-adapted variants, GBM/FRhK and GBM/HFS, differ in their biologic characteristics. While GBM/FRhK showed a strict host range for FRhK-4 cells, GBM/HFS replicated in both cell types (Graff et al., 1994).
        • Hepatitis A virus substrain GBM/HFS :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: Two GBM variants, GBM/HFS and GBM/FRhK, were attained after cell culture propagation. GBM/HFS was propagated eight times in human embryonic kidney cells and then passaged 23 times in HFS cells and is used as an inactivated vaccine. No replication was observed in HFS cells. The two GBM cell culture-adapted variants, GBM/FRhK and GBM/HFS, differ in their biologic characteristics. While GBM/FRhK showed a strict host range for FRhK-4 cells, GBM/HFS replicated in both cell types. Furthermore, GBM/HFS has been shown to be attenuated after inoculation into chimpanzees (Graff et al., 1994).
        • Hepatitis A virus isolate LY6 :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: LY6, subgenotype IA was isolated from a sporadic self-limited Hepatitis A (Hu et al., 2002). Complete sequences of the genomes of two wild type (wt) Human hepatitis A virus (HHAV) isolates, LU38 and LY6 from China were determined and compared with those of wt HHAV isolates AH1, AH2, AH3, FH1, FH2, FH3, GBM, HM175, LA and MBB. Sequence comparison showed that LY6 shared the highest identities of 97.4% for nt (196 differences) and 98.7% for aa (28 differences) with H1 and the lowest identities of 91.2% for nt (642 differences) with HM175 and 97.7% for as (51 differences) with GBM. The subgenotyping revealed that the LU38 and LY6 isolates are of IA subgenotype. The phylogenetic analysis showed that LU38 is closest to AH1 and the LY6 to FH3, suggesting that the epidemiological link of hepatitis A (HA) had developed in China and Japan (Hu et al., 2002).
        • Hepatitis A virus isolate LU38/WR :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: LU38, subgenotype IA was isolated from patient with fulminant hepatitis A virus infection (Hu et al., 2002). Complete sequences of the genomes of two wild type (wt) Human hepatitis A virus (HHAV) isolates, LU38 and LY6 from China were determined and compared with those of wt HHAV isolates AH1, AH2, AH3, FH1, FH2, FH3, GBM, HM175, LA and MBB. Sequence comparison showed that LU38 shared the highest identities of 98.1% for nt (140 differences) and 99.2% for as (17 differences) with AH1, and the lowest identities of 91.4% for nt (741 differences) with HM175 and 98.1% for aa (43 differences) with GBM. The subgenotyping revealed that the LU38 and LY6 isolates are of IA subgenotype. The phylogenetic analysis showed that LU38 is closest to AH1 and the LY6 to FH3, suggesting that the epidemiological link of hepatitis A (HA) had developed in China and Japan (Hu et al., 2002).
        • Hepatitis A virus isolate AH1, isolate AH2, isolate AH3, :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: Genotype IA (Fujiwara et al., 2001) Isolated from patients with self-limited acute hepatitis A virus in Japan. By comparing with genotype IA, wild-type HAV strain GBM, the analysis of whole genomes from six cases showed no specific substitutions between FH and AH. Identical nucleotide sequences were observed at the 3' non-translated region (NTR) in all six cases. In 5'NTR, few nucleotide substitutions were found in FH compared to AH, and in the non-structural protein 2B region, there were more amino acid substitutions in FH than in AH (Fujiwara et al., 2001).
        • Hepatitis A virus isolate FH1, isolate FH2, isolate FH3, :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: Genotype IA (Fujiwara et al., 2001). Isolated from patients with fulminant hepatitis A virus in Japan. By comparing with genotype IA, wild-type HAV strain GBM, the analysis of whole genomes from six cases showed no specific substitutions between FH and AH. Identical nucleotide sequences were observed at the 3' non-translated region (NTR) in all six cases. In the 5'NTR, few nucleotide substitutions were found in FH compared to AH, and in the non-structural protein 2B region, there were more amino acid substitutions in FH than in AH (Fujiwara et al., 2001).
        • Hepatitis A virus strain FG :
          • GenBank Taxonomy No.: 208726
          • Parent: Hepatitis A virus
          • Description: An Italian cytopathic isolate (strain FG) of Hepatitis A. Sequence analysis revealed the presence of mutations common to either adapted or cytopathic variants of HAV. In particular, amino acid deletions in proteins VP1 and 3A were detected. Expression of protein 3A in E. coli showed that the N-terminal deletion renders this protein toxic to bacteria (Beneduce et al., 1995).
        • Hepatitis A virus (strain MSM1) :
          • GenBank Taxonomy No.: 386455
          • Parent: Hepatitis A virus
          • Description: [AUTHORS : Stene-Johansen K , Tjon G, Schreier E, Bremer V, Bruisten S, Ngui SL, King M, Pinto RM, Aragones L, Mazick A, Jensen I P, Sundqvist L, Blystad H, Norder H, Skaug K. TITLE : Molecular epidemiological studies show that hepatitis A virus is endemic among MSM in Europe JOURNAL : Unpublished] (NCBI Entrez).

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