[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.

[The results of serological research to determine hepatitis A and B markers in the blood sera of the population of the Republic of Guinea]. / Rezul'taty serologicheskikh issledovanii po opredeleniiu markerov gepatitov A i B v syvorotakh krovi naseleniia Gvineiskoi Respubliki.

The results of examinations of sera from apparently normal urban and rural residents of the Guinea Republic (GR) for markers of viral hepatitis A (anti-HAV) and B (HBsAg) are presented. The number of HBsAg-positive subjects was 16 +/- 1% (1199 serum specimens were examined by direct enzyme immunoassay, EIA, and HI test), the rate of HBsAg findings in sera from children (less than 16 years) and adults (greater than or equal to 16) did not differ significantly (p less than 0.05). The rate of a HBsAg carrier state did not depend on sex and residence of the subjects under study (p less than 0.05). The detection rate of total (IgM + IgG) anti-HAV antibody was 67 +/- 2% (812 serum specimens were examined by a variant of EIA block). The detection rate and titres of anti-HAV in children were higher than in adults, and in urban residents higher than in rural subjects (p less than 0.05). The results of detection of HBsAg and total anti-HAV antibody in the sera of GR residents are close to those obtained in examinations of sera from the populations of countries bordering GR in Western Africa (Senegal, Mali, Liberia) and are typical of Africa as a whole.

[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.

[Susceptibility of Macaca rhesus to infection with hepatitis A virus strains isolated from man and monkeys]. / Vospriimchivost' makak rezusov k zarazheniiu shtammami virusa gepatita A, vydelennymi ot cheloveka i obez'iany.

The results of infection of Macaca rhesus monkeys with hepatitis A virus (HAV) strains isolated from monkeys and man are presented. After inoculation of monkeys with human NAV strains the infection could not be reproduced whereas simian HAV strains were found to be pathogenic for M. rhesus monkeys both on experimental inoculation and during natural contacts with infected monkeys in the animal house.

[Epizootic hepatitis A among African green monkeys kept in a vivarium]. / Epizootiia gepatita A sredi afrikanskikh zelenykh martyshek, soderzhashchikhsia v usloviiakh vivariia.

The results of observations on the pattern of spread of hepatitis A virus and immune response to it in African green monkeys (Cercopithecus aethiops) kept in the animal house are presented. The infection in the monkeys was found to be characterized by all virological, serological, and biochemical parameters inherent in hepatitis A virus. The results indicated that hepatitis A in monkeys may run both asymptomatic and clinically manifest course, and the spread of infection in the animal house sequentially involves most seronegative animals into the epidemic process.

[Study of human and simian hepatitis A virus isolated by an immunoenzyme method using polyclonal and monoclonal antibodies]. / Issledovanie izoliatov virusa gepatita A chelovecheskogo i obez'ian'ego proiskhozhdeniia immunofermentnym metodom s ispol'zovaniem poliklonal'nykh i monoklonal'nykh antitel.

Hepatitis A viruses (HAV) isolated from man and Old World monkeys varied in their interaction with monoclonal antibodies (MCA) in enzyme immunoassay. All human HAV isolates reacted with the MCA under study (HIC19, H7C27, and K3-4C8), whereas the viruses isolated directly from monkeys did not react with H7C27 MCA and some of them also with H1C19 MCA. Simian HAV strains became capable of reacting with H7C27 MCA and H1C19 MCA after adaptation to cell culture. In tests with human and simian immune sera (polyclonal antibody to HAV) a number of human isolates interacted with human serum antibodies much more intensively and with simian serum antibodies.

[Spontaneous hepatitis A with a fatal outcome in rhesus monkeys]. / Spontannyi gepatit A so smertel'nym iskhodom u makak.

This is the first report of virologically verified spontaneous hepatitis A in M. rhesus monkeys with severe involvement of the liver leading to the death of the animals. In 21 out of 23 dead monkeys morphological lesions in the liver have been characterized as acute hepatitis. In 6 (26%) animals no other pathological processes were found. In 15 animals hepatitis was combined with other diseases (dysentery, parasitic infestations, coronavirus infection). Antigen of hepatitis A virus was detected by an enzyme immunoassay in the intestinal contents of 8 monkeys and in the livers of 3 of them. Immune electron microscopic studies detected in the intestines some virus particles morphologically and antigenically similar to human hepatitis A virus.

[Spontaneous hepatitis similar to hepatitis A in African green monkeys]. / Spontannyi gepatit, skhodnyi s gepatitom A, u afrikanskikh zelenykh martyshek.

Circulation of a virus similar to human hepatitis A virus by antigenic and some other properties was observed among African green monkeys imported from their natural habitats. In some of the monkeys this virus caused a disease similar to hepatitis A in many features.

[Signs of natural infection with hepatitis A in brown macaques (Macaca arctoides)]. / Priznaki estestvennoi infektsii gepatita A u burykh makak.

The results of examinations of stump-tailed monkeys (M. arctoides) held in captivity are presented. The presence and levels of anti-HAV and anti-HAV class M in the blood sera of monkeys were determined by the enzyme-immunoassay (EIA), and alanine aminotransferase (AIAT) activity was measured. HAV in stool specimens collected from the monkeys was detected by immune electron microscopy and EIA. In the first examination, 2 out of 10 monkeys were found to have anti-HAV and one of them to have anti-HAV class M. In repeat examination of 4 monkeys 32 days later, two of them showed an increase in AIAT and 3 had HAV in stools. In the 3rd examination in 91 days, all the four animals had anti-HAV and anti-HAV class M. Besides, three seronegative monkeys out of the ten examined initially, showed only total anti-HAV in 91 days. At the time of the 3rd blood specimen collection, 16 more monkeys were examined and all of these had anti-HAV but not anti-HAV class M. It is assumed that natural infection of stumptailed monkeys in captivity with a virus antigenically identical to HAV is possible.

[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.

[Adaptation of hepatitis A virus strain (JaM-55) originally pathogenic for monkeys to a cell culture]. / Adaptatsiia shtamma virusa gepatita A (IaM-55), iskhodno patogennogo dlia obez'ian, k kletochnoi kul'ture.

The results of adaptation of hepatitis A viral strain JaM-55 to the culture of embryo kidney cells FRhk-4 from macaque Rhesus are presented. The viral strain was isolated from a M. fascicularis suffering from spontaneous hepatitis. Before inoculating the cell culture the virus was passaged twice in the M. arctoides capable of reproducing hepatitis. FRhk-4 cell line inoculation by the monkey liver extract, containing the strain HAV-YaM-55, resulted in isolation of single viral particles of hepatitis A in the preparations obtained at the first 3 passages by the 28-31 day of cultivation. Beginning from the fourth passage the abrupt increase in the number of viral particles and hepatitis A antigen was registered. There were no traces of cytopathogenic effect at any level of viral passages in the inoculated cell culture. The adapted virus contains hepatitis A viral RNA identified by spot hybridization with the cloned cDNA of hepatitis A virus.

[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.

[Viruses in the feces of patients with viral hepatitis and other enterovirus infections]. / Virusy v fekaliiakh bol'nykh virusnym gepatitom i drugimi énterovirusnymi infektsiiami.

Direct and immune electron microscopy was used to determine the frequency of finding of hepatitis A virus (HAV) and other viral agents in feces of patients in relation to the diagnosis and epidemiological situation. HAV-containing excretions from patients were analysed ultrastructurally. The highest frequency of HAV detection was established in patients in a water-borne and food-borne outbreak of hepatitis A (HA) and was 40.9% and 36.9%, respectively. In patients with HA diagnosis in the period of a seasonal rise of HA incidence HAV particles were found in 11.8%, and in the interseasonal period in 5%. Apart from HAV particles, in a small per cent of patients with HA diagnosis adenovirus and enterovirus particles were found. In patients with the disease diagnosed as hepatitis B (HB) only adenovirus and enterovirus particles were found. In contrast to the patients with HAV and HB diagnosis, the patients who were combined into a conditional "non-hepatitis" group were found to have, in addition to HAV (in the period of seasonal rise of HA incidence), adenovirus and enterovirus particles, also particles of astrovirus, coronavirus, and rotavirus. In fecal specimens of patients containing typical HAV particles structures were found resembling individual fragments of empty HAV particles, antibody-covered 17-22 nm and 27 nm spherical structures poorly reacting with antibody.

[Combination of radioimmunological and immunoelectron microscopic methods for detecting hepatitis A virus]. / Kombinatsiia radioimmunologicheskogo i immunoélektronno-mikroskopicheskogo metodov dlia obnaruzheniia virusa gepatita A.

The possibility of combined performance of radioimmunoassay (RIA) and immune electron microscopy (IEM) in one preparation using protein A of Staphylococcus aureus for hepatitis A virus (HAV) detection in fecal specimens from hepatitis A patients within a short time (40-50 min) has been demonstrated. In the examinations of one preparation by RIA and IEM, their sensitivity was found to be approximately similar. According to RIA, a high content of HAV antigen was observed in those preparations where in addition to typical particles there were structures resembling individual fragments of empty HAV particles coated with antibody.

Enzyme-immunoassay in the diagnosis of human hepatitis A: specific and non-specific reactions.

Solid-phase enzyme-immunoassay (EIA) used for the detection of hepatitis A virus (HAV) often reveals a non-specific activity which can be reduced or fully eliminated in the presence of normal serum. The factor responsible for this activity appeared to be a non-viral EIA-active material (NVEAM) that non-specifically reacted with normal serum of some mammalian species (human, monkey, rabbit, cattle). The HAV and NVEAM have been separated by CsC1 gradient centrifugation, where the HAV banded in a narrow zone at 1.34 g/cm3, whereas the NVEAM could be found in a wider zone with an average density of 1.31 g/cm3. Non-immunological character of the non-specific activity was demonstrated by the inhibitory effect of weak non-ionic detergents (0.05% Tween 20 or bile, 1:500). The conditions for preferential binding of the HAV by immune sera and elimination of non-specific reaction have been determined.

[Viral hepatitis with clinical and epidemiological manifestations similar to hepatitis A but of a different etiology]. / Virusnyi gepatit, skodnyi po klinike i épidemiologii s gepatitom A, no otlichaiushchiisia ot nego étiologicheski.

A case of viral hepatitis in man, appearing as the result of infection caused by pooled concentrated suspensions of fecal samples collected from patients having had repeated hepatitis infection during the period of 1-2 years, is described. Though this infection was similar to hepatitis A in many clinical and epidemiological signs, the possibility of its etiologic relationship with hepatitis virus A was positively excluded; there was also no evidence of the participation of hepatitis virus B in the process. Immunoelectron microscopy of excretions collected at the acute stage of the disease revealed the presence of spherical viral particles 27-30 nm in diameter. Antibodies capable of reacting with these particles were detected in the sera of patients having had 2 kinds of hepatitis and in the sera of patients having the 1 kind of hepatitis in the focus of infection where repeated cases of hepatitis had been observed. No such antibodies were found in the sera of patients with hepatitis A alone and in the set of standard sera specific to viruses causing hepatitis A and hepatitis non A, non B. The authors believe that 2 kinds of hepatitis with the fecal-oral mechanism of transmission exist and propose to name their causative agents hepatitis viruses A, type 1 and type 2.

[Human rotavirus in cell culture: its isolation and passage]. / Rotavirus cheloveka v kul'ture kletok: vydelenie i passirovanie.

Rotavirus was isolated from feces of patients and passaged in green monkey kidney cell subculture using the factors affecting the initiation of infection of tissue culture cells with human rotavirus. The effective factors were found to include the presence of low concentrations of trypsin in the infected culture and virus centrifugation of a cell layer which agreed with the data by Almeida et al. (1978) and Shoub and Bertran (1978) obtained in other cell systems. Immune electron microscopy was used to detect the virus in cell cultures and to prove its specificity.