Twenty marmosets, male Callithrix jacchus, were used during this study. Fifteen of the marmosets were inoculated with 5,000 TCID50 of the attenuated XJC13 strain of Junin virus by intramuscular route and five were left as uninoculated controls. Animals were observed for a 420-day period. In order to carry out virologic, hematologic, serologic, and histologic studies the animals were bled and/or killed at different days post infection(pi). Results obtained showed that the attenuated strain produced an infection with no mortality or signs of illness. There was only a slight loss of weight at 18-40 days pi, which was soon recovered. Viremia was present from day 6 to 22, titers peaking at 4.0 log. Viral spread was limited to the lungs, spleen, lymph nodes, and bone marrow in the animal killed on day 14. No virus was found in the organs of the animal killed on day 23, and neither hematologic alterations nor pathologic lesions were seen in these monkeys except for ganglionar hypertrophy with immunoblast proliferation. Antigen was detected by immunofluorescence (IF) in lymph nodes, spleen, adrenals, lungs and brain. Neutralizing antibodies were detected from the third week onward. Protection conferred by the XJC13 strain proved effective when XJC13-inoculated monkeys were challenged with 1,000 TCID50 of the pathogenic XJ strain at days 60 or 380 pi, while normal controls died. When viral persistence was searched for on days 370, 390, and 420 pi, no infectious virus was detected, but viral antigen was seen in certain organs, which, however, lacked tissue damage.(ABSTRACT TRUNCATED AT 250 WORDS)
A clinical and serological study was performed on 267 of 636 volunteers vaccinated against Argentine hemorrhagic fever with the XJCl3 attenuated strain of Junin virus seven to nine years earlier, in order to determine their long-term evolution. This study included a clinical examination, a chest roentgenogram, an electrocardiogram, and the following laboratory determinations: white and red cell count, number of platelets, hematocrit, hemoglobin, sedimentation rate (Katz index), urea, nitrogen, glucose concentration, cholesterol, GOT, GPT, gamma GT, alkaline phosphatase, cholinesterase, and total bilirubin. Neutralization reactions were performed to determine presistence of antibody levels. All clinical and laboratory findings were within normal limits, excluding a long-term pathology attributable to the virus. Of 165 tested sera, 153 (90.3%) had detectable levels of neutralizing antibodies, and the rest had no antibodies after this time. Although these people live in the endemic area, it is considered that only the 9% that had increased antibody levels had suffered a reinfection during the seven- to nine-year period, which acted as a booster. This figure aproximately coresponds to the subclinical infection value found in the region. In the rest, the persistence of antibodies is attributed to the immunization achieved with the vaccine employed.
SUMMARYPersistent infection of MRC-5 cells was established following inoculation with attenuated Junin virus (JV). In the acute phase of the infection both the pathogenic XJ and the attenuated X J0 and XJC13 strains showed severe c.p.e, and free viral titres reached 10 5 p.f.u./ml. Recovery and establishment of persistently infected MRC-5 sublines (MRC-5p0 proved a very common event and seemed to be independent of viral strain, m.o.i, employed or virus passage history. These MRC-5m sublines released virus throughout their life span and infectious centre assays performed at different passage levels with two sublines showed that 5 to 9 ~o of the cells were producing virus. Heterotypic but not heterologous resistance to superinfection developed, as observed in persistent JV heteroploid cell systems. Analysis of released JV showed that attenuation had not been markedly altered, but alteration in plaque morphology under methyl cellulose, appearance of temperature-sensitive mutants and alterations in mouse pathology imply that some properties of J V have been altered. Results presented here stress once again the ability of JV to establish persistent infections. The source and diploid characteristics of MRC-5 cells make them a satisfactory model for JV persistence studies.
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