|
Type Species |
(HAV) |
Physicochemical and Physical Properties
Viruses are very stable, resistant to acid pH and elevated temperatures (60°C for 10 minutes). Buoyant density in CsCl is 1.32-1.34 g/cm3.
There is little similarity between the genome sequences of hepatoviruses and those of other picornaviruses, although the IRES is distantly related to the type 2 IRES. The 5
-NTR contains a 5-terminal hairpin, two putative pseudoknots, and a short (~40 nts) pyrimidine-rich (i.e., not pure polyC) tract upstream of the IRES. Nucleotide sequence identity between different HAV strains is generally greater than 80%. Avian encephalomyelitis virus (AEV) RNA contains the shortest of all picornavirus 5-NTRs, at 494 nts.
In contrast to other picornaviruses, protein 1A is extremely small, does not appear to be myristoylated at its N-terminus, and may not be a component of the mature virus particle. Immature HAV may contain uncleaved 1D2A (PX) precursor protein.
Genome Organization and Replication
The polyprotein contains only a single proteinase (3Cpro). There is no clearly defined L protein, and 2A has no proteolytic activity. The primary cleavage of the polyprotein occurs at the 2A/2B junction, and is catalysed by 3Cpro. The 1D/2A cleavage may be directed by an unknown cellular proteinase, or the VP1 protein may be subject to C-terminal trimming as in cardioviruses. Replication occurs slowly, with little CPE, and with low yields of virus compared to most other picornaviruses. The IRES differs from those of other picornaviruses in that its activity is dependent on intact eIF4G.
Hepatitis A viruses are strongly conserved in their antigenic properties. Most antibodies are directed against a single, conformationally defined immunodominant antigenic site that is comprised of amino acid residues of the VP3 and VP1 proteins on the surface of the virion.
HAV infects epithelial cells of the small intestine and hepatocytes of primates. Virus is predominantly replicated within the liver, excreted via the bile and present in feces in high titer. Viral shedding is maximal shortly before the onset of clinical signs of hepatitis, which probably represents immunopathologically mediated liver injury. Clinical manifestations are fever, jaundice, light stools, abdominal pain, and occasionally diarrhoea. Hepatoviruses generally establish persistent infection when inoculated on to any of a wide range of primate cells in vitro, but persistent infection does not occur in vivo and the viruses are not associated with chronic hepatitis. HAVs can be divided into two distinct biotypes that are phylogenetically distinct and have different preferred hosts (all species of primates: humans, chimpanzees, owl monkeys and marmosets, for one biotype, vs. green monkeys and cynomolgus monkeys for the other). These two biotypes share cross-reacting antigens, but have biotype-specific epitopes that can be distinguished by monoclonal antibodies. AEV causes encephalomyelitis in young chickens, pheasants, quail and turkeys. It can be transmitted both vertically and by the fecal-oral route; field strains are enterotropic.
List of Species Demarcation Criteria in the Genus
Members of a Hepatovirus species have:
|
greater than 70% amino acid identity in the P1, |
|
greater than 70% amino acid identity in 2C + 3CD, |
|
greater than 75% sequence identity over the genome as a whole, |
|
cross-protective antigens, |
|
a defined tissue tropism and host range, |
|
a similar genome base composition which varies by no more than 1%, |
|
a common genome layout. |
Official virus species names are in italics. Tentative virus species names, alternative names ( ), strains or serotypes are not italicized. Virus names, genome sequence accession numbers [ ], and assigned abbreviations ( ) are:
|
Hepatitis A virus (1 serotype, 2 strains) |
(HAV) | |
|
Human hepatitis A virus |
[M14707] |
(HHAV) |
|
Simian hepatitis A virus |
[D00924] |
(SHAV) |
Tentative Species in the Genus
|
Avian encephalomyelitis-like virus (1 serotype) |
[AJ225173] |
(AEV) |
|
|  |
