Liquid-phase and solid-phase radioimmunoassay with herpes simlex virus type 1 nucleocapsids.

Liquid-phase radioimmunoassay (LPRIA) and solid-phase radioimmunoassay (SPRIA) are described utilizing either 125I-labelled or immobilized nucleocapsids (NC) of herpes simplex virus type 1 (HSV-1). These techniques appeared sensitive and specific for quantification of HSV-NC antigens and corresponding antibodies.

Hepatitis B and herpes viral components in the cerebrospinal fluid of chronic schizophrenic and senile demented patients.

Cerebrospinal fluids (CSF) or sera or both from 57 chronic schizophrenics and 18 senile demented patients were examined by various tests for HBsAg. both CSF and serum were positive in 2 schizophrenics while in six HBsAg was detected in the CSF only. Elevated values of circulating immune complexes were found in positive patients. Most CSF positive for HBsAg also contained neutralizing antibodies to Herpesvirus hominis type 1. Ultramicroscopic structures similar to hepatitis B virus (HBV) components and herpesviral particles were visualized in the CSF of one patient on electron microscope (EM) grids coated with anti-human IgG serum. Most HBsAg positive patients appeared to be liver-symptoms-free carriers. In the CSF of a 79 years old senile demented man HBsAg was proved serologically. Several herpesviral particles complexed with globular material and spherical structures for 15 to 25 nm in diameter were visualized in the same CSF on EM grids coated with anti-human IgG serum. The findings support the importance of herpesviruses in mental illness. Penetration of HBsAg through the blood-brian barrier might be involved as an iatrogenic factor in the course of late psychoses.

Early and delayed skin reactivity to solubilized antigens of herpesvirus hominis 1 in psychiatric patients and guinea pigs.

Intradermal tests with a mixture of Herpesvirus hominis 1 (HVH 1) antigens containing quantitated neutralization antigen were done in 39 schizophrenics (SCH), 42 senile demented (DS) persons, 28 alcoholics, neurotics and psychopaths (ANP) and 33 control persons. Local induration, erythema and fading was evaluated according to diameter and intensity after 15 to 30 min for anaphylactic type I reaction, after 5 hr for Arthus type III reaction and after 24 and 48 hr for delayed hypersensitivity (type IV). The diagnosed clinical forms influenced the incidence of positive reactions I, III or IV at the level alpha = 0.01. The incidence of positivity in all reactions (I, III plus IV) was significantly higher in the patients than in the control group. Type I and III reactions were most intensive in ANP and SCH, respectively. Type IV reaction was most pronounced in SCH, including the highest incidence of purple lesions, eventually with a lightly cyanotic target. In the DS group, type IV reaction surpassed the control the least of all patients' groups. Unfavourable side effects of the skin tests were not observed. The importance of repeated contact with HVH 1 for a marked type IV reaction ws confirmed in experimentally infected guinea pigs, which also served for safety tests and selection of antigen preparations.

Selective resistance to togaviral superinfection in mice with tolerant lymphocytic choriomeningitis virus infection.

Mice infected neonatally with lymphocytic choriomeningitis virus (LCMV) developed partial and complete resitance to cerebral superinfection with tick-borne encephalitis virus (TEV) in 10 and 20 days after birth, respectively. This resistance lasted at least till the age of 40 days. LCMV tolerant mice neither succumbed to TEV infection, nor circulated TEV in their blood. Moderate, gradually decreasing TEV titres were detected in the brains and TEV-induced brain interferon was lower than in control mice of the same age. TEV superinfection caused a significant depression of the blood titre of tolerated LCMV while the titres in the brains remained equal to those in tolerant but not superinfected mice. LCMV tolerant mice showed a similar resistance to another togavirus (chikungunya) but not to encephalitogenic picorna-, herpes- and rhabdoviruses.

Latent herpesvirus hominis 1 in the central nervous system of psychotic patients.

Cerebrospinal fluids (CSF) from 35 patients with senile or presenile dementia and from 13 patients with schizophrenia and related syndromes were examined in cell cultures with the aim to isolate Herpesvirus hominis 1 (HVH 1) or other viruses. Serum and CSF antibodies to HVH 1 and/or interferon in the patients indicated a recent HVH 1 antigenic or viral activity. In the CSF of two senile demented patients and of one patient with schizoaffective psychosis, agents of low virulence, causing a cytopathic effect in 3 or 4, but not more, subsequent passages were detected and identified as HVH 1 by immunofluorescence. A focus of cells containing HVH 1 antigen at the cell membrane and in cytoplasm was visualized by immunofluorescence in an explant from nucleus amygdalae from 1 of 6 patients with schizophrenia and related syndromes examined. In the original biopsy materials, various virus-like structures were found in nuclei and cytoplasm of astrocytes and neurocytes and in axons in the neuropil.

Assay of interferon and viral antibodies in the cerebrospinal fluid in clinical neurology and psychiatry.

Cerebrospinal fluids (CSF) of 245 neurological and 194 psychiatric patients were tested for viral antibodies and interferon. Complement dependent neutralizing antibodies to Herpesvirus hominis 1 were found in the CSF of patients with encephalitis (50.6%), meningitis (35.4%), lesions of peripheral nerves (36.9%), sclerosis multiplex (41.2%), schizophrenia (31.9%), senile dementia (51.4%), mental retardation (11.1%), ethylism (43.5%). Neutralizing antibodies to tick-borne encephalitis virus were found in the CSF of 38% patients with encephalitis, in 14% meningitis, 11% lesions of peripheral nerves and also in 5.6--11.8% of psychiatric patients. In encephalitis, meningitis and in lesions of peripheral nerves were found in the CSF frequently plaque neutralizing antobidies to the tick-borne orbivirus Lipovník, complement-fixing antibodies to lymphocytic choriomeningitis virus and hemagglutination inhibiting antibodies to measles virus. In multiple sclerosis were detected CSF antibodies to measles virus (44%), Herpesvirus hominis 1 (41.2%) and Lipovník virus (52.6%). In neurological patients were observed CSF antibodies simultaneously to two or three viruses in 16.7 to 40.6%, while in psychiatric patients in zero to 4.6%. CSF interferon was found in psychiatric patients with an equal or even higher incidence (33.7 to 57.1%) than in the neurological patients (29.6--38.6%, in multiple sclerosis only 16.7%). Non-interferon virus inhibitors were excluded. The evaluation of the ratio of serum and CSF titers of viral antibodies and of interferon indicated local synthesis of both in the central nervous system -- with the exception of antibodies to Herpesvirus hominis 1 in CSF of some patients with very high titres in serum and probable lesions of the blood brain barrier.

Viral superinfection in cells carrying an arenavirus and/or a togavirus.

Four lines of the same L-cell clone were transferred 60 times in parallel: uninfected cells, a line carrying lymphocytic choriomeningitis virus (LCMV), another one carrying tick-borne encephalitis virus (TEV) and one carrying both viruses. In double persistency, LCM and TEV were suppressed and stimulated, respectively. Cell multiplication rates were comparable in all four lines. Single LCMV persistence caused marked resistance of L cells to superinfecting viruses from various taxonomic groups, but this phenomenon was abolished or even reversed to increased sensitivity in the cell line with co-persisting LCMV plus TEV.

Suppression of an arenavirus by a togavirus in experimental acute double infection.

Lymphocytic choriomeningitis virus (LCMV) and tick-borne encephalitis virus (TEV) were inoculated in young and old chick embryo cell (CEC) and in L-cell cultures at various multiplicities per cell, simultaneously or 17 hr apart. The yield of infective LCMV was inhibited in double infection, most in old CEC with elevated interferon mechanisms, and least in L cells producing no interferon. In young CEC, TEV-induced interferon was stimulated by coinfecting LCMV; LCMV alone never has induced interferon. The reproduction of TEV was little affected. In doubly infected L cells the fluorescent antibody techniques revealed more cells positive for each viral antigen than in single infections, but the yield of LCMV per one antigen-positive cell was decreased. The course of TEV infection in cerebrally infected mice was not changed by co-infection with LCMV. The titre of LCMV in the brains of doubly infected mice was markedly suppressed when compared with LCMV monoinfection. High interferon levels in brains of all mice infected with TEV were not affected by LCMV co-infection.

Activation of latent herpesvirus hominis in explants of rabbit trigeminal ganglia: the influence of immune serum.

More than fifty albino rabbits were inoculated into the right scarified cornea with 10(7) PFU of the Kupka strain of human herpes virus type 1 (HHV-1). At intervals ranging from 4--280 days post infection (p.i.), both gasserian ganglia, both trigeminal nerve trunks and pieces from brain stem and from both corneas were explanted. Activation of the latent HHV-1 was found mainly in the homolateral ganglion tissue, but also in explants originating from the opposite ganglia. Within 24--72 hours, prior to the release of virus into the medium, one infectious unit of HHV was recovered from 10(4)--10(5) cells of the ganglion explant. In addition, a few neurons and satellite cells revealed the presence of virus-specific antigens when the explants were examined by immunofluorescence in serial sections. If the gangia were explanted in the presence of immune serum, the virus recovery rate was at least twice lower as compared to the virus activation in explants kept in the absence of immune serum.

Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation.

Complement-requiring neutralizing antibodies to herpes simplex type 1 virus (HSV 1) in titres from 2 to greater than 16 were detected in the cerebrospinal fluid (CSF) of 47% senile patients with various forms of dementia, but in none of mentally retarded adolescents and adults suffering from various neurologidal diseases. Also the incidence of HSV 1 serum antibodies in elevated titres (larger than or equal to 512) was increased in senile demented patients (61%) as compared with persons in normal senium (31%), normal adults (15%), mentally retarded adolescents (17%) and prisoned felons with low IQ (45-47%).