Nora V. Galassi

Argentine Hemorrhagic Fever: A Biologic Marker

Mortality rates and viral replication in blood and brains of Wistar rats between 6 h and 26 days of age inoculated with two strains of Junin virus of different virulence were compared. Viral growth curves in brains showed no differences between strains. However, differences in mortality rates were significant among rats between 1 and 3 days of age. When the intracerebral (i.c.) route was used, high mortality rates were induced by the attenuated XJC13 strain and low mortality rates were induced by the pathogenic XJ strain. On the other hand, when the intraperitoneal or subcutaneous route was used, mortality rates were reversed: low for the attenuated strain and high for the pathogenic one. The use of different doses of each virus and the application of various routes of inoculation in 2-day-old rats showed that 10(3) TCID50 by the i.c. route resulted in the greatest difference in mortality rates.

Brain inflammatory exudate in Junin virus-infected rats: Its characterization by the immunoperoxidase (PAP) technique

Morphologic changes in cyclophosphamide (CY)-suppressed vs. control non-suppressed new-born rats infected i.c. with XJC13 strain of Junin virus were compared and the cells involved in CNS lesions were identified by the PAP technique. Fifty per cent of the control rats exhibited widespread cerebral necrosis vs. only 15% of the immunosuppressed animals. The first cells to reach Junin virus-infected CNS in controls were T lymphocytes, which destroyed viral antigen-laden target neurons and astrocytes. B lymphocytes and macrophages, presumably attracted by viral antigen and/or by lymphokines, made their appearance a day or two later. Activated macrophages phagocytosed necrotic cells and perhaps exerted a cytotoxic effect upon target neural cells, whereas the actual role of B lymphocytes requires further explanation. In CY-treated rats, cerebral lesions were smaller and the cellular exudate, though similar, proved much scantier than in controls. A similar extent of cerebellar necrosis was observed in both groups.

Immunosuppression in Experimental Junin Virus Infection of Mice

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.

Maturation of suckling rat response to SRBC

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.

Protection Conferred against Junin Virus Infection in Rats

2-day-old Wistar rats intracerebrally infected with the XJC13 strain of virus exhibited a 5% survival rate which rose to 71% after immune serum treatment. Brain viral titers were relatively unaffected by this treatment. Histologic studies showed necrosis in the cerebellum and brain cortex with mononuclear cell infiltration in both treated and nontreated groups. Beginning on day 16 postinfection, however, intracerebral perivascular gliosis foci and mild meningeal congestion were minimal in the treated animals. These findings imply that passively transferred humoral immunity leads to prompt recovery in this experimental model.