The Hepatitis A virus (HAV), or Hepatovirus A, is a member of the viral family Picornaviridae. It takes human and vertebrates as its natural hosts. HAV achieves about 1.4 million worldwide symptomatic cases per year and is the cause of Hepatitis A (formerly known as infectious hepatitis, an acute infectious disease of the liver). HAV is different from other picornaviruses, it targets the liver and can continue act as a source of mortality even after a successful vaccine. HAV can't shut down the protein synthesis of host cells, which is also different from other picornaviruses. HAV is usually stable both physically and genetically. However, its codon usage is highly deoptimized and its growth in tissue culture is usually poor, which makes the HAV very difficult to study.
HAV isolates all belong to a single serotype, seven genetic groups now have been defined, four for humans (genotype number: I-III, and VII) and three for simian (genotype number: IV-VI). For human genotype I-III, six subtypes are identified as IA, IB, IIA, IIB, IIIA, and IIIB. Most of the human isolates belong to the genotype I, and genotype III have been reported to exist in both humans and simians.
Fig.1 The structure of HAV capsid (PDB Data base)
HAV is a nonenveloped picornavirus which contains only a single-stranded RNA packed within a protein capsid. The structure of HAV capsid has been solved by X-Ray Crystallography in 2015 (Xiangxi Wang et al. Nature. 2015 Jan 1; 517(7532): 85–88.). Major proteins of HAV are VP1-3, which contain eight-stranded anti-parallel β-barrels, follow the expected pseudo T=3 arrangement and form the pentameric assemblies to construct the capsid. The extend surface of HAV capsid is smooth without canyon. And the HAV capsid particle surface is negatively charged in total.
Fig.2 Negative stain electron microscopy of HAV particles (Xiangxi Wang et al. Nature. 2015 Jan 1; 517(7532): 85–88.)
HAV enters human and other natural hosts through blood and fecal-oral. After ingestion, HAV were transferred into blood system through epithelium of the oropharynx or intestine. Then the HAV is able to be carried into the liver tissues, where its target cell lies. The multiply of HAV occurs in the cytoplasma of the hepatocytes and liver macrophages cells (Kupffer cells). The virus exits the host cell through lysis or viroporins. Then the virus was released in stool through bile. Its incubation period is 15–50 days and the appearance of symptoms or anti-HAV IgM antibodies in the blood is about 11 days later than the release of HAV in large quantities.
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