Cynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hällnäs), which causes nephropathia epidemica in humans in western Europe. During the first week after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild proteinuria and microhematuria. Histopathologic changes during the first 7 weeks after infection were largely confined to abnormalities in medullary tubular cells of the kidneys, which coincided with the demonstration of viral antigen and viral RNA. The development of different classes of virus-specific plasma antibodies to the respective viral antigens were similar to those observed in humans with nephropathia epidemica. This first description of a nonhuman primate model for hantavirus infection shows that the cynomolgus macaque provides a suitable model with which to study the pathogenesis of Puumala virus infections and to evaluate new diagnostic methods, immunization strategies, and therapies.

Serum samples were collected from 27 individuals who had been infected with a member of the genus Hantavirus in the Netherlands or Belgium during the last 15 years. These samples were tested in an immunofluorescence assay (IFA) and two enzyme-linked immunosorbent assay (ELISA) systems, using different virus strains that represented each of the four recently proposed serotypes of this genus. The serum samples from 11 individuals who had been infected through contacts with laboratory rats showed the highest reactivities with Hantaan virus (serotype I) and SR-11 (serotype II) in the IFA and ELISA systems. The samples of 16 individuals who had probably been infected through contacts with wild rodents showed the highest reactivities with Hällnäs virus (serotype III) in the IFA. All except two of these also showed the highest reactivity with Hällnäs virus in the two different ELISA systems.