Junin virus infection of Callithrix jacchus: pathologic features.

Infection of Callithrix jacchus, a New World primate, with the prototype strain of Junin virus produced a severe disease. The animals developed multifocal hemorrhages and characteristic microscopic lesions such as meningoencephalitis, interstitial pneumonia, lymphocytic depletion of lymphatic tissue, hepatocytic necrosis, and a variable decrease in bone marrow cellularity. High virus concentrations correlated with lesions, and with the presence of viral antigenic determinants as revealed by immunofluorescent methods. With the exception of central nervous system damage, the morphological features and immunohistochemical and viral findings were similar to those recorded in human Argentine hemorrhagic fever.

Nasal and intrathalamic inoculations of primates with Tacaribe virus: protection against Argentine hemorrhagic fever and absence of neurovirulence.

Callithrix jacchus marmosets were inoculated by different routes with two stocks of Tacaribe virus, one from suckling mouse brain and another from human diploid MRC5 cells. All 12 primates inoculated by nasal route developed neutralizing serum antibodies without any clinical signs. All 6 primates receiving the mouse brain-Tacaribe virus were protected against lethal challenge with pathogenic XJ strain of Junin virus, while protection was also conferred in 4 out of 6 primates receiving the diploid cell-Tacaribe virus stock. Intramuscular (i.m.) inoculation also elicited antibodies and conferred protection to 4 primates receiving the diploid cell-virus stock. Intrathalamic (i.t.) inoculation of mouse brain-virus stock caused no clinical signs or histopathologic changes in groups of 3 primates each examined on days 33 and 90 post-infection (p.i.). All primates developed antibody response, but no virus could be detected in their brain. Thus, Tacaribe virus proved harmless and immunogenic in Callithrix jacchus and protected most marmosets against challenge with the lethal XJ strain of Junin virus.

Junin virus infection of Calithrix jacchus: haematological findings.

Haematological changes produced by experimental Junin virus infection of a platyrrhine monkey, Callithrix jacchus were studied. Normocytic and normochromic anaemia appeared after 7 days post infection (p. i.), and increased steadily until day 21 p. i. Reticulocytes and circulating erythroblasts were elevated during the anaemia, reached a peak on day 7 p. i., and disappeared later. Platelets and leukocytes showed a significant decrease from days 14 and 18 p. i., respectively. These alterations could be attributed to the damage of bone marrow and lymphatic tissue.

[Study of bone marrow in experimental Argentine Hemorrhagic Fever. Role of the megakaryocyte]. / Estudio sobre la médula ósea de cobayo en la Fiebre Hemorrágica Argentina. Papel del megacariocito.

In previous morphological studies on bone marrow of guinea pigs infected with Junin virus, the coexistence of viral particles, antigens and cytopathic effects were observed in megakaryocytes. In addition, bone marrow is one of the organs where highest virus titers were obtained. However, although other myeloid cells presented intense cytopathic effect, viral antigens were observed only in reticular cells and virus particles were seen sporadically associated with immature cells. This study was designed to investigate if bone marrow infetivity was due mainly to megakaryocyte infection. Megakaryocyte obtained from infected bone marrow were concentrated in albumin gradients by gravitational sedimentation. Enriched fractions were studied by immunofluorescense /IF) and virus titration. Results showed that fractions containing 8, 6.4 or 15 % of megakaryocytes had titers of 3.81, 4.23 and 2.7 LD50/mñ respectively. On the contrary in depleted fractions (0 % megakaryocytes), titers were 0,5 to 1 log lower (Fig. 1, Table 1). By IF, Junin antigens were located in the cytoplasm of 70 % of megakaryocytes and also in reticular cells, but not in other cell types. These results suggest that megakaryocytes suffer a productive infection that may well account for the thrombocytopenia observed in this experimental infection. However, the detection of infectivity in other cells, in absence of viral antigens and particles remains to be explained.

[Detection of laboratory infections caused by Junín virus using the neutralization and immunofluorescence technics comparatively]. / Detección de infecciones de laboratorio por virus Junín utilizando comparativamente las técnicas de neutralización e inmunofluorescencia.

To study Junin virus infection among laboratory workers and to compare immunofluorescence and neutralization tests, blood samples were taken from 48 individuals, of which 42 were considered high risk personnel. None of the 16 low risk workers exhibited antibodies. Neutralizing antibodies were detected in 15 high risk laboratory workers. Nine of the latter were already known to carry antibodies from a previous survey in 1978. Titers detected were either at previous levels or slightly higher. Of the remaining 6 out of the 15 positive cases, 3 showed mild clinical and subclinical infection, equivalent to a 12% incidence rate over the 1978-1980 period. An adequate correlation was observed between neutralization and immunofluorescence test: 66.6% for both positive tests and 97.1% for both negative tests. Although the immunofluorescence test ies easier to perform the neutralization test appears to be more reliable clinically. The overall prevalence rate of neutralizing antibodies among non-vaccinated personnel was almost 19%, which warns against the health hazard involved in Junin virus handling.

[Infection of New World primates with Junín virus. IV. Aotus trivirgatus]. / Infección de primates del nuevo mundo con virus Junín. IV. Aotus trivirgatus.

Owl monkeys (Aotus trivirgatus) were inoculated with XJ, a pathogenic strain of Junin virus, seeking new animal models for Argentine Hemorrhagic Fever. Nine monkeys were inoculated intramuscularly with 30 or 300,000 TCID50 of junin virus. Hematological and virological studies showed no alteration in blood elements such as red cell, reticular cell and platelets, up to 28 days after inoculation. Hemoglobin and hematocrit determinations also remained constant. However, significant neutropenia was seen at day 11 and minimal viremia was detected in some animals during the second and third week post-inoculation. No clinical or behavioral modifications were observed during the eighty-days observation period. Non-specific necropsy findings included pyelonephritis, pneumonitis, liver abscess and eosinophilic spleen infiltrate. All of these findings seem to be unrelated to Junin virus inoculation. No virus was present in organs of animals killed 29, 57 or 85 days post-inoculation. All nine owl monkeys developed serum neutralizing antibodies by day 22. It is concluded that the owl monkey suffers a subclinical infection when inoculated with Junin virus, similar to that seen in other primate species (Saimiri sciureus and Alouatta caraya).