Pathogenetic Aspects of Hepatitis A Virus Infection in Enterally Inoculated Marmosets

Authors:
  • KKKrzysztof K. Krawczynski
    Krzysztof K. Krawczynski
  • DBDaniel W. Bradley
    Daniel W. Bradley
  • BMBert L. Murphy
    Bert L. Murphy
  • JEJames W. Ebert
    James W. Ebert
  • TAThomas E. Anderson
    Thomas E. Anderson
  • IDIrene L. Doto
    Irene L. Doto
  • ANAdam Nowoslawski
    Adam Nowoslawski
  • WDWillem Duermeyer
    Willem Duermeyer
  • JMJames E. Maynard
    James E. Maynard
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Abstract
Experimental hepatitis A virus (HAV) infection was studied in marmosets after enteral (intragastric) inoculation with special reference to the primary sites of HAV replication and immunopathology of the disease. The experiment was carried out using 28 Saguinus mystax negative for antibody to HAV (anti-HAV) and with statistically uniform baseline values of serum isocitrate dehydrogenase (SICD) activity. Each animal was infected with 1 ml of a 15% w/v stool suspension that was derived from marmosets infected with the third or fourth passage of the MS-1 strain of HAV. The incubation period measured by the first significant SICD) elevation was 32 days in 11 of 13 marmosets. The animals were sacrificed 2, 4, 7, 11, 14, 18, 23, 28, and 32 days after inoculation and 1, 4, 8, 14, 21, 28, and 35 days after SICD elevation. HAV antigen, immunoglobulins, complement, and fibrin were identified in the liver, eight segments of the gastrointestinal tract, lymphoid system, and kidneys. HAV antigen was found only in the cytoplasm of hepatocytes and in gallbladder tile. These findings indicated that the liver was the sole and primary site of virus replication. Combined immunomorphologic and histopathologic observations also revealed that HAV antigen localization was associated with the sites of hepatocellular damage. There was no immunomorphologic evidence for humoral immune clearance of HAV antigen in the liver, lymphoid system, or kidneys.