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Experimental hepatitis E: pathogenesis in cynomolgus macaques (Macaca fascicularis)
C F Longer1, S L Denny, J D Caudill
1Dept. of Virus Diseases, WRAIR, Washington DC, 20307-5100.
The Journal of Infectious Diseases
|September 1, 1993
Summary
This study details experimental hepatitis E in macaques, revealing an early phase of virus replication and liver damage, followed by an antibody response and persistent pathology. Understanding hepatitis E virus (HEV) pathogenesis is crucial.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- The pathogenesis of experimental hepatitis E remains incompletely understood.
- Accurate documentation of disease progression is essential for developing effective interventions.
Purpose of the Study:
- To meticulously document the chronological events in experimental hepatitis E.
- To elucidate the interplay between hepatitis E virus (HEV) replication, host immune response, and liver pathology.
Main Methods:
- Intravenous inoculation of cynomolgus macaques with HEV-containing material (bile or feces).
- Comprehensive analysis of serum, bile, and liver specimens using light microscopy, immune electron microscopy, immunofluorescence microscopy, EIA, and PCR.
- Monitoring of histopathologic changes, HEV antigen (HEVAg), HEV RNA, alanine aminotransferase (ALT) levels, and antibody to HEV (anti-HEV).
Main Results:
- Histopathologic changes, HEV antigen (HEVAg) in the liver, HEV in bile, and elevated ALT levels were observed by the third week post-inoculation.
- Widespread pathologic changes occurred in the fourth week, with peak ALT values and the appearance of anti-HEV noted in the fifth or sixth week.
- HEVAg diminished by the sixth week, while pathological changes persisted, indicating a protracted disease course.
Conclusions:
- Experimental hepatitis E exhibits a biphasic course: an initial phase of HEV replication and hepatitis onset, followed by a later phase characterized by anti-HEV production and progressive liver damage.
- The findings support a model where viral replication drives initial hepatitis, and the subsequent immune response correlates with disease progression.