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