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Hepatitis A Virus

Virology

Hepatitis A virus (HAV) belongs to the genus Hepatovirus within the Picornaviridae family. Its single-stranded, positive-sense RNA genome is approximately 7.5 kb in length, with a lengthy 5’ untranslated RNA segment covalently linked to a small virally encoded protein, VPg (or 3B), at its 5’ terminus. Its RNA genome is packaged within an icosahedral protein capsid composed of 60 copies of each of 3 major structural proteins, VP1, VP2, and VP3. A fourth viral capsid protein (VP4), which is essential for virion formation, is not detected in mature viral particles. Seven HAV genotypes have been identified; four genotypes (I, II, III, and VII) are of human origin, and three (IV, V, VI) are of simian origin.

HAV structural proteins and their topography. Fig.1 HAV structural proteins and their topography. (Stuart, 2019)

Two Forms of HAVs

  • “Naked” HAV Virions

    • Naked, non-enveloped HAV virions shed in the faeces of infected individuals are small, 27 nm in diameter, icosahedral protein capsids within which the RNA genome is packaged. The antigenic structure of the capsid is highly conserved, and all human hepatoviruses form a single serotype.

  • Quasi-Enveloped HAV Virions

    • Only quasi-enveloped eHAV viruses are found in the blood of infected persons and in supernatant fluids of infected cell cultures. Quasi-enveloped eHAV virions are between 50 and 110 nm in diameter. The enveloping membranes completely occlude the capsid, preventing detection of capsid antigen in the absence of detergents and protecting it from antibody-mediated neutralization. Quasi-enveloped virions resemble exosomes and present no viral glycoproteins (peplomers) on the membrane surface, a feature that distinguishes them from conventional enveloped viruses.

Two different forms of infectious HAV virions. Fig.2 Two different forms of infectious HAV virions. (Shin, 2018)

Pathogenesis

  • The virus appears to replicate first in the gastrointestinal tract and then spreads to the liver.
  • The virus first multiplies in the intestinal epithelium and then enters the bloodstream and then migrates to liver parenchymal cells.
  • HAV attaches to liver cell through Ig-like cellular receptor on the host cell and enter inside the cell by receptor-mediated endocytosis.
  • Inside the endosome, the virus releases VPg protein which creates pores on the endosomal membrane and releases viral genome in the host’s cytoplasm and damages the hepatocytes.
  • The classic findings in the hepatocytes include mononuclear infiltrate, balloon-ing, degeneration, and acidophilic (Councilman-like) bodies.

Symptom

The clinical manifestations of HAV infection range from asymptomatic infection to acute liver failure, but it does not progress to chronic hepatitis. The development of symptomatic hepatitis is associated with patient age. Relatively few children under 6 years of age manifest hepatitis symptoms, whereas the majority of adults develop symptoms that persist for 2-8 weeks. The onset of hepatitis A is often abrupt with fever, malaise, nausea or vomiting, abdominal discomfort, and then dark urine and jaundice. Less commonly, pruritus, diarrhea, arthralgia, or skin rash develop.

Epidemiology

  • Worldwide, the endemicity of HAV infection varies according to regional hygienic standards; the highest prevalence of infection occurs in regions with the lowest socioeconomic levels.
  • Most transmission occurs among close contacts in households and extended family settings.
  • HAV transmission has been associated with contaminated food and water.

Prevention and Treatment

  • Vaccines

    • Vaccines have been developed to cure and prevent further infection of the hepatitis A virus. There are two types of hepatitis A vaccines. Both activate antibodies either injecting inactivated Hepatovirus A or to live but weakened virus.

  • Treatment

    • There is no specific medication or treatment for hepatitis A.

Anti-HAV Products and Services

Creative Biolabs now provides numerous HAV antibodies targeting various proteins such as VP-1, VP-3, core protein, surface protein, etc. We also provide other hepatitis virus antibodies, referred to as types B, C, D and E. Visit the ViroAntibody supply page for further details. We also provide fully comprehensive services including ViroAntibody Neutralization Assays, ViroAntibody Discovery Services, ViroAntibody Engineering Services, ViroAntibody Customized Services. Please feel free to contact us for further information.

References

  1. Stuart, D.I.; et al. Hepatitis A virus capsid structure. Cold Spring Harb Perspect Med, 2019, 9(5) :a031807.
  2. Shin, E.C.; Jeong, S.H. Natural history, clinical manifestations, and pathogenesis of hepatitis A. Cold Spring Harb Perspect Med, 2018, 8(9): a031708.

All products and services are intended for Research Use Only, and NOT to be used in diagnostic or therapeutic procedures.

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