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Tick-borne encephalitis (TBE) virus was isolated from the brains and spinal cords, blood, livers, lymph nodes and kidneys from Macaca rhesus monkeys showing acute and subacute fatal encephalitis. In subacute encephalitis, virus titres in the CNS were lower than in acute disease (3.0--6.2 against 3.8--8.3 log LD50/ml). TBE virus localization in chronic encephalitis was largely the same as in acute and subacute disease. In monkeys with a chronic course and stable paralysis of the upper extremity, infectious TBE virus was isolated on day 383 from subcortical ganglia and spinal cord. In lymph nodes and spleen, it could be detected only by a combination of methods (co-cultivation in association with fluorescent antibody technique and complement-fixation test, explantation of organ fragments) more sensitive than is the inoculation of mice with organ homogenates. TBE virus was detected by the same methods on day 90 in the CNS and internal organs of a monkey with chronic encephalitis in the stage of remission.

Fifty monkeys (Macaca rhesus) inoculated with tick-borne encephalitis (TBE)virus intracerebrally or subcutaneously were examined. The efficiencies of different virus detection methods at 90 to 783 days after inoculation were: explantation of organs - 41.2%; co-cultivation of trypsinized organ cells and indicator cells in the presence of 5-bromo-2-iododeoxyuridine with detection of the virus-specific antigen by immunofluorescence - 43.7%, detection of infectious virus and complement-fixing antigen - 13.6%; immunofluorescence examination of organ impression smears - 29.3%; and examination of organ homogenates with detection of virus pathogenic for mice - 1.7%. the latter method was the least sensitive for the detection of persisting TBE virus, in spite of that in the first 3 weeks of infection its efficacy was 88.1% in examinations of clinically ill monkeys and 23.8% in the inapparent form of the infection.

In 28 Macaca rhesus monkeys inoculated subcutaneously (s.c.) with different strains and mutants of tick-borne encephalitis (TBE) virus and developing asymptomatic infection, TBE virus and the virus-specific antigen were found at different intervals up to 302 days post inoculation (p.i.) in the CNS and internal organs (liver, spleen, lymph nodes, kidneys). When cyclophosphane (CP) was used as an immunosuppressor, no significant changes in virus distribution were observed with the exception of more frequent isolations at early intervals from kidneys and at late intervals from spleen. With or without CP administration virus was found in the spinal cord at 3--6 days, in the cerebellum and subcortical ganglia at 11--14 days, in the cerebral cortex at 19 days p.i. Early after inoculation the virus was more frequently isolated from the CNS than from the internal organs; later (93--302 days p.i.) the persisting virus or virus-specific antigen were predominantly found in internal organs. The set of sensitive methods used facilitated to detect the persistence of TBE virus in noninfectious form in monkeys with asymptomatic infection.

The properties of tick-borne encephalitis (TBE) virus persisting for 90-383 days after intracerebral and subcutaneous inoculation of Macaca rhesus monkeys were studied, namely (1) the type of infection produced directly in the tissues of the experimental monkeys; (2) the activating effect of co-cultivation and explantation procedures; and (3) the phenotype of the isolates by a set of markers. The virus was detected and analysed in 52 instances. Directly in monkey tissues the virus induced a productive infection rarely (5.8%) but more frequently (71.2%) an abortive infection detectable by immunofluorescence (presence of virus-specific antigen). In 23% of instances a nonproductive infection was observed in monkey tissues. Like abortive infection it could be activated by the co-cultivation of cells and explantation procedures. The latter exerted a more marked activating effect than co-cultivation. The strains isolated from monkey tissues in productive infection or activated by explanation or co-cultivation were heterogeneous in their properties. The following virus phenotypes were found: virus highly virulent for mice, cytocidal and antigenically complete; a cytocidal virus of low virulence, possessing haemagglutinin; and a cytocidal virus apathogenic for mice, devoid of haemagglutinin but synthesizing complement-fixing antigen and an antigen detectable by immunofluorescence.