Simulation of Viral Hepatitis E in Marmosets.

We developed a model of hepatitis E virus infection in common marmosets (Callithrix jacchus) and determined optimal route of infection, duration, clinical and virological characteristics of infection in laboratory animals. Using this model, we demonstrated that replication of hepatitis E virus primarily occurs in the liver, while virus replication presumed to take place in the intestine was not confirmed in this experiment.

[Role of hepatitis A and E viruses in the development of autoimmune diseases].

The mechanisms of development of autoimmune diseases may be associated with a complex of genetic, immune, hormonal, and infectious factors. Autoimmune diseases include a wide range of systemic and organ-specific diseases, including autoimmune hepatitis (AIH). It is currently assumed that the pathogenesis of AIH is due to compromised immune regulation in the presence of an exogenous triggering factor. Exogenous factors, such as viruses, may be triggers of AIH. There may be different ways of initiating an autoimmune response by viruses, which includes nonspecific T-lymphocyte activation and molecular mimicry. There is much evidence supporting the initiating role of hepatitis viruses in the development of AIH and other autoimmune diseases. The development of AIH symptoms during hepatitis A and E virus infections has been described elsewhere. The creation of animal models of viral hepatitis is required to confirm the hypothesis that the viruses trigger the development of AIH and other autoimmune manifestations.

[Primate models of human viral hepatitis].

The paper summarizes the updates available in the literature and the authors' own data on the etiology of hepatitis, its models, and experimental studies on susceptible simian types. A comparative analysis of the etiological agents--the causative agents of simian and human hepatitis will give a better insight into the evolution of its viruses.

[Viral hepatitis E. The problems of its study].

The paper presents the results of investigations of hepatitis E (HE), which have been made at the Department of Viral Hepatitides, M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences. M. S. Balayan's discovery of hepatitis E virus permitted etiological interpretation of the cases of so-called non-A, non-B hepatitis with its fecal and oral transmission. The detection of antibodies to HE virus among different groups of the population of Russia (i.e. a hepatitis E nonendemic region of the world) suggests that they are frequently detected in the absence of disease notification. The fact that viral HE RNA has been detected in the pigs and wild boars inhabiting in the country is evidence in favor of an assumption that the virus is spread among these animals. The hypothesis for HE as a zoonosis is discussed in the paper.

[The biochemical indices of the blood serum in experimental hepatitis A in tamarins]. / Biokhimicheskie pokazateli syvorotki krovi pri éksperiemental'nom gepatite A u tamarinov.

Serum biochemical parameters were studied in 42 healthy wild-caught adult tamarins (S. mystax), males and females, to determine the normal values. Blood samples were drawn repeatedly, and the serum was tested for aspartate aminotransferase, alanine aminotransferase, isocitric dehydrogenase, serum glucose, serum urea, triglyceride, cholesterol, albumin, and total protein. The results indicated that serum chemistry values were similar to those reported as normal for both humans and other Callitrichidae species. The study of serum biochemical parameters in tamarins with experimental hepatitis A indicated that serum enzyme activities alone reflected the hepatic damage, while other biochemical parameters were of no real clinical importance. The experimental results showed the levels of serum urea to be indicative of the pathological involvement of the kidneys in experimental hepatitis A in some cases.

[The immunogenicity of a cultured inactivated hepatitis A vaccine]. / Immunogennost' kul'tural'noi inaktivirovannoi vaktsiny gepatita A.

A trial of inactivated hepatitis A viral vaccine of heteroploid cell culture origin is described. The vaccine preparation was tested in guinea pigs and tamarins. The animals were immunized intramuscularly four or three times, respectively. The efficacy was judged by induction of anti-HAV antibody persisting for at least 12 months in guinea pigs, and development of immunity to subsequent virus challenge (monkeys only). The challenge dose of HAV was unable to produce any signs of HAV infection in the vaccinated tamarins, although the booster effect was observed in some animals. The study demonstrated that the tested batches of the vaccine were highly immunogenic.

[The modelling of hepatitis A and of enterally transmitted non-A, non-B hepatitis (hepatitis E) in Saguinus mystax tamarins]. / Modelirovanie gepatita A i énteral'no peredaiushchegosia gepatita ni A, ni B (gepatita E) na tamarinakh Saguinus mystax.

A comparative study of hepatitis infection caused by human hepatitis A virus (MS-1 strain), simian hepatitis A virus (AGM-27 strain), and enterically transmitted non-A, non-B hepatitis virus (Tashkent-1435 strain) was carried out. Susceptibility of tamarins to the AGM-27 and Tashkent-1435 as well as to MS-1 strain was demonstrated. All the strains induced an acute infection characterized by serum alanine aminotransferase (ALT) elevation, virus excretion and antibody response. Certain differences in the course of infection caused by these strains were observed in the duration of the incubation period and ALT profiles.

[A trial of a cultured inactivated vaccine against hepatitis A on Saguinus mystax tamarins]. / Ispytanie na tamarinakh Saguinus mystax kul'tural'noi inaktivirovannoi vaktsiny protiv gepatita A.

An experimental batch of inactivated hepatitis A vaccine was prepared using hepatitis A virus (HAV), HAS-15 strain, adapted to cell culture and purified by ultracentrifugation. The vaccine was tested in tamarins immunized intramuscularly three times one month apart. Three tamarins received a vaccine preparation containing 10 ng of immunogen each, three--100 ng each, and three animals were used as controls. The efficacy was judged by the anti-HAV antibody response in the vaccinated animals and development of immunity to subsequent virus challenge two months after the last immunization. The criteria of infection were: elevation of serum alanine aminotransferase, fecal excretion of HAV and production of specific antibody of IgM class. The immune response to 10 ng of the immunogen was lower than to 100 ng, however, both doses produced complete resistance to infection. The booster effect was observed in animals receiving 10 ng of the immunogen. The vaccine batch under study in the indicated doses was shown to have a good immunogenic potency and protective activity for tamarins.

[Development of an infection in monkeys as a result of their sequential natural and experimental exposure to the hepatitis A virus]. / Razvitie infektsii u obez'ian v rezul'tate posledovatel'nogo estestvennogo i éksperimental'nogo zarazheniia ikh virusom gepatita A.

The development of spontaneous outbreak of hepatitis A (HA) among African green monkeys kept under strict isolation conditions was studied. It was shown that in the case of introduction of HAV the infection involved all the susceptible monkeys, running a course with and without any increase in the level of activity of serum alanine aminotransferase (ALT) After inoculation of commercial gamma-globulin only the infection without the ALT activity increase developed and some monkeys had no signs of HA at all. Experimental reinfection with HAV was produced in monkeys having anti-HAV titres of less than or equal to 1:3500.

[Hepatitis A in Macaca fascicularis and M. arctoides infected by the Java monkey-55 strain of hepatitis A virus]. / Gepatit A u iavanskikh i burykh makak pri ikh zarazhenii shtammom virusa gepatita A IaM-55.

The results are presented dealing with experimental inoculation of M. fascicularis and M. arctoides with a strain of hepatitis A virus (HAV), YaM-55, isolated from a M. fascicularis with spontaneous hepatitis A, and parallel experiments on inoculation of these monkey species with HAV preparations (strain HAS-15) obtained as a result of the strain propagation in FRhK-4 cell culture and with specimens from human hepatitis A patients containing HAV particles. The YaM-55 strain of HAV was found to be capable of producing an infectious process quite similar to HA in the inoculated seronegative M. fascicularis and M. arctoides. Two different isolates of HAV derived from humans and the HAS-15 strain of HAV propagated for a long time in FRhK-4 cell culture failed to induce a disease in these monkey species. The classification of the YaM-55 strain with HAV was verified by specific serological studies and by molecular hybridization with cloned cDNA of HAV.

[Reproduction in monkeys of non-A, non-B hepatitis transmitted via the fecal and oral routes]. / Vosproizvedenie na obez'ianakh gepatita ni A, ni B, peredaiushchegosia fekal'no-oral'nym putem.

The paper presents the results of experimental infection of monkeys with virus-containing specimens from a patient with fecal-oral non-A-non-B hepatitis; the study was aimed at the determination of the possibilities of simulating this infection. Of the 8 monkeys infected with the material containing virus particles of fecal-oral non-A-non-B hepatitis 5 monkeys developed the infection manifested in virus excretion in fecal specimens, a rise in the level of serum aminotransferases, and typical histological lesions of the liver tissue. The infection could also be produced by inoculation of monkeys with virus-containing material from monkey. The above results indicate that the virus isolated from a human suffering from fecal-oral non-A-non-B hepatitis may induce in experimentally infected Macaca fascicularis monkeys a pathological process simulating viral hepatitis.

[Spontaneous hepatitis in the crab-eating macaque exposed to immunodepressants]. / Spontannyi gepatit u iavanskoi makaki, podvergnutoi vozdeistviiu immunodepressantov.

A case of spontaneous hepatitis was detected in experiments aimed at working out the conditions for reproduction of the immunosuppressed state in Macaca fascicularis with the purpose of subsequent infection of these monkeys with non A non B hepatitis virus transmitted by the fecal-oral route. One of 6 monkeys at the 8th day of the experiment was found to have developed an increase in the level of serum aminotransferases which grew progressively reaching high values by day 14. Fecal specimens from this monkey collected on the 5th day and later contained spherical virus-like structures 27 nm in diameter, antigenically identical with hepatitis A (HAV) virus. In the other 5 monkeys, no similar structures were found in fecal specimens throughout the experiment. The monkey with the signs of hepatitis was sacrificed on the 16th day of experiment, i. e. on the 8th day from the onset of hyperenzymemia. Immune electron microscopy of extracts of hepatic tissue and fecal specimens collected from this monkey has revealed 27 nm particles antigenically identical with HAV. The bulk of viral particles from the liver sedimented in cesium chloride buoyant density zone of 1.32 g/cm3, and from fecal specimens in the zone of 1.36 g/cm3. In the liver of this monkey, histological changes were found which are observed in acute hepatitis, and HAV antigen in hepatocyte cytoplasm was detected by the fluorescent antibody technique. It is suggested that the spontaneous disease of this monkey was due to natural infection with HAV which could be provoked by experimental immunosuppression.