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Infectivity studies of hepatitis A and B in non-human primates
Abstract:
We have induced hepatitis A in marmosets of the subspecies Saguinus mystax following primary inoculation with human serum containing the MS-1 strain of hepatitis A virus (HAV) and in 3 further marmoset subpassages using infective marmoset serum from each preceding passage. In each passage acquisition of serum antibody against 17 nm virus-like particles recovered from acute illness stools of human volunteers who developed hepatitis following inoculation with the MS-1 strain of HAV, as well as from acute illness stools of hepatitis A cases from a common source epidemic of heaptitis A in Arizona could be demonstrated by immune electron microscopy (IEM). Particle-containing stool filtrates from the latter epidemic also induced hepatitis in chimpanzees after intravenous inoculation. Inoculation of partially purified particles from a single banding in CsCl2 has further resulted in the induction of hepatitis in S. mystax marmosets. We have successfully induced hepatitis in a series of chimpanzees inoculated with sera containing hepatitis B surface antigen (HBsAg) of varying subspecificities. Susceptibility appears universal in animals who are initially lacking in serum antibody (anti-HBs) and antibody induced following experimental infection is homologous in subspecificity to the subspecificities of the antigenic coat components of the HBsAg in the inoculum. Results of cross challenge experiments indicate that animals developing hepatitis following inoculation of HBsAg of one subspecificity set in the d/y-w/r system do not again develop hepatitis following inoculation with HBsAg of the alternate subspecificity set.
Insights
Hepatitis A virus (HAV) was successfully induced in marmosets and chimpanzees. Experimental infections confirmed antibody responses and provided insights into hepatitis B virus (HBV) subspecificities.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Hepatitis A virus (HAV) and hepatitis B virus (HBV) are significant human pathogens.
- Animal models are crucial for studying viral hepatitis pathogenesis and developing countermeasures.
Purpose of the Study:
- To establish a marmoset model for hepatitis A virus (HAV) infection.
- To investigate the induction of hepatitis in chimpanzees using hepatitis B surface antigen (HBsAg) with varying subspecificities.
Main Methods:
- Induction of hepatitis A in Saguinus mystax marmosets via inoculation with MS-1 strain HAV.
- Demonstration of anti-HAV antibodies using immune electron microscopy (IEM).
- Induction of hepatitis in chimpanzees using HBsAg with defined subspecificities.
Main Results:
- Successful induction of hepatitis A in marmosets and subsequent serial passages.
- Detection of virus-like particles and induction of homologous antibody responses in experimentally infected animals.
- Chimpanzees inoculated with specific HBsAg subspecificities developed homologous antibody responses and resistance to homologous challenge.
Conclusions:
- Marmosets are a suitable model for studying HAV infection and immune responses.
- Experimental HBV infection in chimpanzees elicits homologous antibody responses and cross-protection within specific subspecificities.
- Understanding HBsAg subspecificities is important for vaccine development and managing HBV infection.