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A new attenuation marker to distinguish a virulent strain (XJJV) from an attenuated strain (XJC13JV or XJOJV) of Junin virus by means of the humoral and cellular responses to unrelated antigens was studied in guinea pigs. Strain XJJV suppressed the humoral immune response, as shown by the lower titers of precipitating antibody to ovalbumin. The concomitant decrease in serum complement level contributed to a milder Arthus cutaneous reactivity. In contrast, the attenuated strains did not decrease the humoral response. The pathogenic strain suppressed cell-mediated immunity, as demonstrated by decreased contact sensitivity to 2,4-dinitro-1-fluorobenzene and by depression of delayed skin reactions to tuberculin purified protein derivative. When attenuated strains were used, such suppressive effects were not observed. For virulent strain XJJV, virus replication in lymphoid organs and immunosuppressive effects were correlated. These findings provide a further means to differentiate between virulent and attenuated strains of Junin virus for the purpose of vaccine control of Argentine hemorrhagic fever.

Otherwise resistant adult mice were rendered susceptible to intracerebral Junin virus (JV) infection only when a staggered cyclophosphamide (CY) schedule was used. Forty-five-day old Balb/c mice, intracerebrally JV-infected and immunosuppressed with four 50 mg/kg body weight CY doses at days -1, +1, +4, +6 (day 0: viral infection) developed a lethal disease (86.6 per cent mortality) with high CNS viral titers and brain lesions. Neutralizing antibodies were absent throughout, while immunofluorescent antibody levels were considerably diminished. The transfer of hyperimmune serum conferred partial though significant protection on CY-treated animals but no correlation was found between CNS viral titers and mortality since in both infected CY-treated and untreated mice similar brain viral content was found. This was also confirmed by immune spleen cell transfer at day 0 where the clearance achieved was unable to modify the time course of the disease. Feasible mechanisms explaining recovery from JV infection by means of the protective effect of antibodies and the cell-mediated clearance are discussed.

The immune response of the Buffalo/Sim rat to heterologous sheep red blood cells (SRBC) was studied here. The earliest time of response to 10 9 SRBC, the most suitable inoculation route and the behavior to challenge were determined. The intraperitoneal (ip) proved more effective than the subcutaneous (sc) route, since serum agglutinins became detectable in low titers in animals inoculated at 6–7 days of life by the former route and at 12 days by the latter. No splenic plaque-forming cells (PFC) were found in rats immunized ip at 2 days of age, and strong inhibition developed on challenge at day 14 post-inoculation (pi) (agglutinin titers at day 7 pi: 0.71 ± 0.47 vs 4.6 ± 0.51 in unprimed controls; PFC/10 7 cells at day 5: 122.21 ± 36.17 vs 3,977.38 ± 777.5 in unprimed controls). Serum agglutinin formation was also decreased, though to a lesser degree, when: a) animals were challenged at 30 or 60 days of age; b) both priming and challenge took place by sc route; or c) antigen dose was lowered to 10 7 or 10 5 SRBC. Mechanisms interpreting observed behavior are discussed.

Brain tissues of newborn mice infected intracerebrally with Junin virus were examined by light and electron microscopy in order to elucidate the pathogenesis of Junin virus infection as well as the effect of antithymocyte serum (ATS) on the development of the disease.

The effect of Junin virus infection on the active and passive delayed hyper-sensitivity of Jones Mote type in guinea pigs was studied. It was shown that in both types of hypersensitivity there is a suppression of the cutaneous reaction.

The effects of cyclophosphamide (CY), anti-mouse thymocyte sera, oxisuran, and cytosine arabinoside were evaluated in adult and newborn mice infected with Junin virus. Treatment with CY was the most effective, Adult mice, which are not normally susceptible to intracerebral infection with 10(3) LD50 of Junin virus, were rendered susceptible by treatment with an adequate dose and schedule of CY. However, CY-treated newborn mice were protected from death. This animal model may be suitable for use in pathogenesis and protection studies.

A DISEASE of unknown etiology appeared a few years ago in the northwestern part of the Province of Buenos Aires. The clinical aspects were first described by Arribalzaga (1) and later by Duva (2), who suggested that it may be of leptospiral origin. The disease appeared again in 1958, and in May of that year we went to the city of Junin to study its clinical and etiological features. This study was the first to provide evidence of the virological nature of the causative agent (3). Later, Margni and co-workers, on the basis of little evidence, presented the opinion that poisoning by dieldrin, aldrin, or other products, might be an auxiliary factor (4). At a special meeting held in the University of Buenos Aires on December 19, 1958, we presented a full report of our work with the disease, defining it as new in Argentina and giving additional evidence of its virus etiology (5,6). This work has since been confirmed by other investigators (7). The clinical descriptions, which we had previously published, were recently confirmed by studies of the disease produced by inoculation of human volunteers. This research was conducted by two groups, working independently, and their reports appeared at about the same time (7,8).