[Modeling hepatitis A in monkeys (results and prospects)].
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Biomedical subjects
Publications and source records attributed to Z V Shevtsova.
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The prolonged (up to 2 years) complex observation of 11 rhesus macaques (Macaca mulatta) with spontaneous hepatitis A and 14 rhesus macaques with experimental hepatitis A developing after their intravenous and/or oral infection with human hepatitis A virus (HAV). Both natural and experimental infection took a chronic course (15-18 months). In 13 monkeys showing morphological changes in the liver during the whole period of the disease elevated enzyme levels in the blood and virus shedding in feces were periodically observed. Only one monkey had acute hepatitis A which lasted 1.5 months. In 11 monkeys the disease took an undulating course with 1-2 relapses when virological, biochemical and morphological signs of the disease could be detected. Seroconversion was observed in all monkeys. Anti-HAV IgM antibodies were retained for not more than 6-7 months and total anti-HAV antibodies, during the whole period of observation. Relapses were found to induce no antibody formation. Evidence on the prolonged (up to 12-16 months) persistence of HAV in primates was obtained for the first time.
Detailed description of liver damage in two species of macaques (rhesus and fascicularis) and green monkeys with spontaneous hepatitis A (HA) induced by the virus similar to human hepatitis. A virus (HAV) is given. Evolution of histological changes was followed by serial liver biopsies. The picture of the hepatitis in the above monkey species resemble that of human NA as well as HA in other monkey species susceptible to HAV. Only in 8 of 21 monkeys the disease lasted for 2-5 months, others exhibited undulating and lingering course which lasted 8-19 months from the beginning of the infection. The lingering course of the infection was caused by HAV persistence in the host with its periodical elimination in faeces.
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The focus of this paper is characterization of Hepatitis A experimental model obtained for the first time in rhesus monkeys (M. mulatta) infected with fecal isolate from a patient with Hepatitis A (HAV-H1). Monkeys were susceptible to oral and intravenous routes of HAV inoculation. The disease could be reproduced regularly in 4 passages as a result of which HAV strain continuously pathogenic for M. mulatta has been established. All 17 infected monkeys developed Hepatitis A with characteristic (except jaundice) patterns: shedding of virus with the stool, elevations of serum alanine aminotransferase level, appearance of IgM anti-HAV, morphological changes developed in the liver. Our data have demonstrated that the course of experimental Hepatitis A infection in M. mulatta is similar (in many respects) to that observed in man.
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Virologic, serologic, biochemical, and morphological data characterizing spontaneous hepatitis A (HA) in cynomolgus macaques (Macaca fascicularis) and green monkeys (Cercopithecus aethiops) are reported. Experimental HA was induced in macaques as a result of infection with human hepatitis A virus (HAV-h). Disease similar to human HA was induced in cynomolgus macaques by HAV isolates from spontaneously sick rhesus (M. mulatta) and green monkeys. This experimental model of HA in macaques can be used for vaccine and anti-viral preparation testing.
Morphological, virological and serological data characteristic of spontaneous hepatitis A in macaques and green monkeys have been presented. The disease similar to human hepatitis A was induced in M. iris macaques, with the virus isolated from spontaneously infected rhesus monkeys. Experimental model of hepatitis A in macaques is likely to be used for the testing of vaccines and antiviral preparations.
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Two lymphoblastoid cell lines were established from baboons with lymphoid disease. Cells of these lines were positive for complement and Fc receptors but lacked sheep cell receptors, theraby indicating B-cell origin. The cells contained antigens which cross-reacted with Epstein-Barr virus (EBV), viral capsid antigen (VCA), early antigen (EA) and membrane antigen (MA). Both lines released virus with in vitro transforming activity for lymphocytes of several primate species including humans. Cells of the original lines and transformed cells showed no staining for EB nuclear antigen (EBNA). The virus was neutralized by anti-MA positive baboon and human sera. Baboon virus and EBV had different but overlapping in vitro host-cell ranges.
The results of pathomorphological investigation of the disease in small laboratory animals experimentally induced by the EMC-70 strain of encephalomyocarditis virus isolated from monkeys are presented. Irrespective of the mode of virus injection, the newborn and juvenile mice developed some lesions in the brown fat, transverse-striated muscles, as well as in the brain and heart. In guinea pigs the changes were characterized by the development of severe myocarditis and encephalitis accompanied by viral antigen accumulation. The disease induced by the EMC-70 strain could not be differentiated from the Coxsackie infection by the pathomorphological data. This fact should be taken into consideration in solving some problems pertinent to pathoanatomical diagnosis of viral diseases.
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