[Virus persistence in hepatitis A in monkeys]

Area of Science:

• Hepatology
• Virology
• Primate Models

Background:

• Hepatitis A virus (HAV) infection typically presents as acute hepatitis.
• The potential for chronic HAV infection and its long-term sequelae in animal models remains less understood.

Purpose of the Study:

• To investigate the long-term clinical and virological course of Hepatitis A in non-human primates.
• To determine the persistence and pathogenicity of HAV in experimentally and spontaneously infected monkeys.
• To establish the etiological link between HAV persistence and chronic disease manifestations.

Main Methods:

• Long-term observation of cynomolgus monkeys (Macaca fascicularis) and African green monkeys (Cercopithecus aethiops).
• Assessment of spontaneous and experimentally induced Hepatitis A.
• Utilized radioimmunoassay, enzyme immunoassay, immune electron microscopy, and molecular hybridization to detect HAV persistence.
• Monitored liver morphology, alanine aminotransferase (ALT) levels, and fecal HAV shedding.

Main Results:

• Two forms of Hepatitis A were identified: acute and chronic, with some animals exhibiting 2-6 waves of undulating chronic illness.
• Relapses (1-3) occurred at 2-4 or 6-11.5 months post-infection.
• Persistent HAV was detected for 7-20 months, with morphological liver changes lasting 7-28 months.
• Persisting HAV was confirmed to remain pathogenic in the primate hosts.

Conclusions:

• Hepatitis A virus can establish persistent infections in non-human primates, leading to chronic disease and late relapses.
• This study provides the first virological evidence demonstrating the etiological role of HAV in chronic Hepatitis A and its relapses.
• Persistent HAV in monkeys retains its infectivity and pathogenicity, highlighting the complexity of Hepatitis A virus infections.