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Additional evidence for more than one agent of human non-A, non-B hepatitis. Transmission and passage studies in
Abstract:
Evidence supporting the existence of two agents of human non-A, non-B hepatitis was obtained by the inoculation of chimpanzees sequentially with serum from a chronically infected human (Inoculum I) and with fibrinogen prepared from pooled plasma (Inoculum IV), each of which had transmitted non-A, non-B hepatitis to humans. Passage inoculations of serum samples obtained during the acute stages of chimpanzee infections transmitted by either the agent in Inoculum I or IV also transmitted non-A, non-B hepatitis to additional chimpanzees. Transmission and passage of the agent in Inoculum IV were conducted in chimpanzees which previously had recovered from infection by the agent in Inoculum I. Cytoplasmic tubules in hepatocytes, which have been described during non-A, non-B hepatitis, were observed by electron microscopy in liver biopsies obtained during all infections transmitted by the agent in Inoculum I. These cytoplasmic tubules were not detected in liver biopsies from chimpanzees infected by Inoculum IV, except in one chimpanzee inoculated by Inoculum IV without prior exposure to the agent in Inoculum I. The cytoplasmic tubules observed in this study were found to be composed of transverse bands arranged with a periodicity of approximately 17 nm. These studies suggest that two different agents or distinct serotypes of human non-A, non-B hepatitis may have been present in these inocula, although reactivation of latent infection or reinfection could not be ruled out completely.
Insights
This study provides evidence for two distinct agents causing human non-A, non-B hepatitis. Differentiating these hepatitis agents was achieved through chimpanzee inoculation and electron microscopy analysis of liver tissues.
Area of Science:
- Hepatology
- Virology
- Electron Microscopy
Background:
- Non-A, non-B hepatitis is a significant public health concern.
- Previous studies suggested the existence of multiple causative agents.
- Understanding the distinct agents is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate the potential existence of two distinct agents responsible for human non-A, non-B hepatitis.
- To differentiate these agents based on their transmission patterns and associated cellular changes in chimpanzees.
Main Methods:
- Chimpanzee inoculation with two different inocula (Inoculum I and Inoculum IV) derived from human hepatitis cases.
- Sequential passage of the virus in infected chimpanzees.
- Electron microscopy of liver biopsies to identify characteristic cellular changes, such as cytoplasmic tubules.
Main Results:
- Inoculum I consistently produced cytoplasmic tubules in hepatocytes, a known marker for non-A, non-B hepatitis.
- Inoculum IV did not induce these tubules, except in a control chimpanzee, suggesting a different etiological agent.
- Successful transmission and passage were confirmed for both inocula in chimpanzees.
Conclusions:
- The findings strongly suggest the presence of at least two distinct agents or serotypes of human non-A, non-B hepatitis.
- The observed differences in cytoplasmic tubule formation support the distinction between the agents in Inoculum I and IV.
- While alternative explanations like reinfection cannot be entirely excluded, the evidence points towards distinct etiological entities.