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The object of this paper was to determine the influence of cyclophosphamide immunosuppression on the mortality of 40-45 day old Balb/c mice infected intracerebrally with a pathogenic strain of Junin virus, using different administration schedules. Up to 200 mg/kg of cyclophosphamide were not toxic. Results show that, unlike in other experimental models, three or four 50 mg/kg cyclophosphamide doses given both before and after viral infection were required to break-down resistance to Junin virus (90-96.5% mortality vs. 8% in controls). Taking into account the effect of cyclophosphamide on the cell populations involved in the immune response, causes likely to lead to the greater susceptibility of the suppressed adult mouse to Junin virus are discussed.

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Delayed-type-hypersensitivity (DTH) response "in vivo" is commonly evaluated by the footpad swelling test (FPST). High doses of Sheep Red Blood Cells (SRBC) are known to produce negligible DTH, while low doses lead to optimal sensitization. As expected FPST values obtained in Balb/c mice using 10(6) or 10(8) SRBC as sensitizing doses, showed that in 9 out of 10 batches from individual rams, the former dose resulted in higher values than the latter. However, only 3 out of the above 9 exhibited statistically significant differences between immunizing doses (Table 1). Therefore, in our hands, the accuracy of FPST is highly dependent on the SRBC source. We suggest the need of testing individual SRBC batches at both dilutions before use.

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Delayed-type-hypersensitivity (DTH) response [quot ]in vivo[quot ] is commonly evaluated by the footpad swelling test (FPST). High doses of Sheep Red Blood Cells (SRBC) are known to produce negligible DTH, while low doses lead to optimal sensitization. As expected FPST values obtained in Balb/c mice using 10(6) or 10(8) SRBC as sensitizing doses, showed that in 9 out of 10 batches from individual rams, the former dose resulted in higher values than the latter. However, only 3 out of the above 9 exhibited statistically significant differences between immunizing doses (Table 1). Therefore, in our hands, the accuracy of FPST is highly dependent on the SRBC source. We suggest the need of testing individual SRBC batches at both dilutions before use.

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The object of this paper was to determine the influence of cyclophosphamide immunosuppression on the mortality of 40-45 day old Balb/c mice infected intracerebrally with a pathogenic strain of Junin virus, using different administration schedules. Up to 200 mg/kg of cyclophosphamide were not toxic. Results show that, unlike in other experimental models, three or four 50 mg/kg cyclophosphamide doses given both before and after viral infection were required to break-down resistance to Junin virus (90-96.5

mortality vs. 8

in controls). Taking into account the effect of cyclophosphamide on the cell populations involved in the immune response, causes likely to lead to the greater susceptibility of the suppressed adult mouse to Junin virus are discussed.

RESUMEN

The object of this paper was to determine the influence of cyclophosphamide immunosuppression on the mortality of 40-45 day old Balb/c mice infected intracerebrally with a pathogenic strain of Junin virus, using different administration schedules. Up to 200 mg/kg of cyclophosphamide were not toxic. Results show that, unlike in other experimental models, three or four 50 mg/kg cyclophosphamide doses given both before and after viral infection were required to break-down resistance to Junin virus (90-96.5

in controls). Taking into account the effect of cyclophosphamide on the cell populations involved in the immune response, causes likely to lead to the greater susceptibility of the suppressed adult mouse to Junin virus are discussed.

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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).

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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).

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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).

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The susceptibility of the marmoset Callithrix jacchus to Tacaribe virus infection was investigated to perform cross-protection studies between Junin and Tacaribe viruses. Five marmosets inoculated with Tacaribe virus failed to show any signs of disease, any alterations in erythrocyte, leukocyte, reticulocyte, and platelet counts or any changes in hematocrit or hemoglobin values. No Tacaribe virus could be recovered from blood at any time postinfection. Anti-Tacaribe neutralizing antibodies appeared 3 weeks postinfection. The five Tacaribe-infected marmosets and four noninfected controls were challenged with the pathogenic strain of Junin virus on day 60 post-Tacaribe infection. The former group showed no signs of disease, no viremia, and no challenge virus replication, whereas the control group exhibited the typical symptoms of Argentine hemorrhagic fever, high viremia, and viral titers in organs. Soon after challenge, the Tacaribe-protected marmosets synthesized neutralizing antibodies against Junin virus. These results indicate that the marmoset C. jacchus can be considered an experimental model for protection studies with arenaviruses and that the Tacaribe virus could be considered as a potential vaccine against Junin virus.

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Cuatro primates neotropicales de la especie S. sciureus fueron inoculados con la cepa patogena prototipo XJ del virus Junin a fin de determinar su susceptibilidad a la misma. Dos S. sciureus fueron inoculados por via intramuscular con 10(3) DL50 de dicha cepa, y las dos restantes con 10 (5) DL50. Independentemiente de las dosis de virus administrada, ninguno de los monos inoculados mostro signos clinicos de enfermedad hasta la fecha en que se los sacrifico (entre 82 y 178 dias despues de la infeccion), para realizar estudios histologicos y de persistencia viral. No se detectaron modificaciones significativas en el numero de hematies, reticulocitos, plaquetas y leucocitos. La busqueda de virus en sangre entre los 7 y 36 dias despues de la infeccion, dio resultados negativos. Tampoco se detecto la presencia de virus infeccioso, de antigeno viral o de modificaciones histologicas, en los organos de los animales sacrificados. Tres de los 4 monos infectados desarrollaron anticuerpos neutralizantes humorales antivirus Junin

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