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Subacute sclerosing panencephalitis (SSPE) agent in hamsters
Abstract:
A hamster-adapted SSPE agent was shown to cause a productive infection in weanling hamster brain, which changed to a cell-associated or defective infection coincident with the appearance of measles antibodies in serum. Antibodies to measles hemagglutinin, hemolysin and neucleocapsid antigens developed in serum, which also contained neutralizing activity for regular measles virus. The agent recovered from the brains prior to the appearance of serum antibodies was infectious in cell-free media, capable of rapidly destroying Vero-cell cultures and able to progressively destroy primary hamster brain cultures. In contrast the agent recovered from the brain after serum antibodies were present, was infectious only within cells destroyed Vero-cells ineffectively and spread slowly through primary brain tissue cultures releasing minute amounts of extracellular virus intermittently. Nevertheless, infected giant cells in the primary brain cultures contained both the HA & HL measles antigens in their cytoplasmic membranes. This in vivo conversion of a productive to a cell-associated cerebral infection appeared to be caused by the host antibody response and may mirror the initial events of human SSPE and possibly other slow or latent measles infections of the CNS.
Insights
A hamster-adapted SSPE agent shifted from productive to cell-associated infection after measles antibodies appeared. This host antibody response may mimic early human Subacute Sclerosing Panencephalitis (SSPE) and other latent measles infections.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Subacute Sclerosing Panencephalitis (SSPE) is a severe, slow neurological complication of measles virus infection.
- The pathogenesis of SSPE and other latent measles infections of the central nervous system (CNS) remains incompletely understood.
- Understanding the interplay between the virus and host immune response is crucial for deciphering disease progression.
Purpose of the Study:
- To investigate the in vivo and in vitro effects of host antibody response on a hamster-adapted SSPE agent.
- To characterize the changes in viral infectivity and cell association during infection.
- To explore potential parallels between the observed phenomena and human SSPE.
Main Methods:
- Infection of weanling hamsters with a hamster-adapted SSPE agent.
- Monitoring of serum measles antibodies and viral characteristics in brain tissue.
- In vitro culture of infected brain cells (Vero and primary hamster brain cultures).
- Analysis of viral infectivity, cell destruction, and antigen presence (HA & HL) in cell cultures.
Main Results:
- The SSPE agent initially caused productive infection, transitioning to cell-associated/defective infection upon antibody appearance.
- Pre-antibody agent was cell-free infectious, rapidly destroying cell cultures.
- Post-antibody agent was cell-associated, inefficiently destroying cells with intermittent extracellular virus release.
- Infected giant cells showed measles HA & HL antigens in cytoplasmic membranes.
Conclusions:
- Host antibody response in vivo induces a shift from productive to cell-associated SSPE agent infection.
- This conversion may represent early events in human SSPE and other latent CNS measles infections.
- The findings highlight the critical role of the immune system in modulating viral persistence and disease manifestation in the CNS.