Roberto M. Arana

Argentine hemorrhagic fever. Alterations of the complement system and anti-Junin-virus humoral response.

Abstract We investigated immunologic mechanisms and the role of complement in the pathogenesis of Argentine hemorrhagic fever, a disease caused by the Junin virus, a member of the arenavirus group. Total serum complement activity was reduced to 68 per cent of control values in patients with severe or moderate disease (P<0.001). C2, C3 and C5 values were also low (12 to 60 per cent) during the early acute period of the disease. However, serum C4 content was increased to 160 per cent of the control values in the same patients. Total complement activity returned to normal with clinical and laboratory recovery, at the time of detection of antibodies against Junin virus. C1q reactive material was found in four of 19 cases and no relation to the evolution of the disease could be established. These results suggest that immune complexes are not important in the pathogenesis of Argentine hemorrhagic fever, but that activation of the complement system has a role. (N Engl J Med 299:216–221, 1978)

Modification of sarcolemmal enzymes by chagasic IgG and its effect of cardiac contractility

It has been shown that sera from chagasic patients contain an antibody which binds to beta-adrenoceptors of myocardium and modulates their activity. Chagasic IgG triggered a marked stimulation of myocardial contractility with an increase in intramyocardial cyclic AMP and inhibition of (Na+ + K+)-ATPase activity. Both the mechanical and enzymatic effects of the IgG could be prevented by beta-adrenoceptor blockade or after the absorption of chagasic IgG with turkey red blood cells. In contrast, guinea pig red blood cells were unable to remove the beta-reactivity of chagasic IgG. These findings suggest that the IgG from chagasic patients increases myocardial contractility by behaving as a beta-agonist. This effect is likely related to stimulation of the adenylate cyclase coupled to the cardiac beta-adrenoceptor.

Ultrastructural and immunohistochemical study of the human kidney in Argentine Haemorrhagic Fever

In six lethal cases of Argentine Haemorrhagic Fever (AHF) a disease caused by Junin virus, kidney samples were studied by means of immunofluorescent and electron microscopic techniques. — The ultrastructural studies showed that the distal and collecting tubes presented a large number of virus like intracytoplasmic particles. Those particles were present in the lumen of the endoplasmic reticulum cisternae and showed two distinct morphological aspects. Some of them were of high electron density and contained a few granules. The others were larger in size, electron lucid, and contained a variable number of ribosome like granules. Both types of particles originated from the endoplasmic reticulum wall by a process of budding. The presence of these particles was coincident with a severe cell damage which lead to necrosis and desquamation; and with large quantities of Junin virus antigen as demonstrated by immunofluorescence. — On the basis of these observations it is assumed that in AHF the cell damage is due to direct viral replication within the affected cells.

Presence of viral particles in the salivary gland of Calomys musculinus infected with Junin virus by a natural route.

Calomys musculinus, a wild cricetid rodent, is one of the main reservoirs of Junin virus. Six of these animals were infected by being placed in close contact with animals that had been experimentally infected with the virus. They were sacrificed at 10, 15 and 20 months after contact, and their salivary glands were studied by ultrastructural, immunohistochemical and virological methods. Two animals developed chronic viremia and low titers of complement-fixing antibodies. These animals were the only ones that had high viral titers in salivary glands and blood and viral antigen and particles in salivary glands. Although some of the other animals had viremia at the beginning of the experiment, it was absent 5 months later. Complement-fixing antibodies developed in all animals. On the basis of these findings, we assumed that the salivary gland is an important site of viral synthesis and excretion. This type of chronic infection, with persistent viremia and virus shedding, is possibly important for virus perpetuation in nature and transmission to man.

Description of a BHK/21 cell line persistently infected with Junin virus: its use in diagnostic procedures.

A BHK/21 cell line persistently infected by an arenavirus is described. During four consecutive passages, 30-45% of the cells showed granular cytoplasmic antigen by indirect immunofluorescence, employing both Argentine hemorrhagic fever convalescent sera and sera from animals immunized with Junin virus. Virus isolated from the cells killed suckling mice but not adult mice and protected guinea pigs against further challenge with the virulent prototype strain of Junin virus. Neutralization tests showed that the virus isolated from the cells was neutralized by anti-Junin virus antisera. The usefulness of this cell line in rapid immunofluorescent serological procedures is described.

A rapid method for detecting Junin virus viremia in the guinea pig.

A method for detecting Junin virus viremia in guinea pigs is described. The method consists of infecting BHK-21 cells with blood samples from infected guinea pigs; 48 h later, Junin virus antigens are detected in the cells by indirect immunofluorescence. Application of this technique to patients with Argentine hemorrhagic fever may lead to the quickest method for the virologic diagnosis of this disease.