A Macaque Model for Hantavirus Infection

Abstract

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.

Hantavirus Infection in SCID Mice.

“…-; Negative, ±; Rarely positive, +; Positive. 8,14,20,24]. Only the newborn animal has been shown to suffer lethal symptoms [15,30].…”

“…Although the characteristic symptoms of HFRS and HPS differ, both diseases are transmitted from rodent reservoirs which are persistently infected without symptom [13,17]. Various animal experiments have been carried out to examine the mechanisms which regulate the pathogenicity of hantavirus to rodents, and to examine the availability of an animal model for HFRS [7,8,14,20,24]. Systemic infection leading to lethal outcome was observed only among newborn mice [15,21], newborn rats [30] and nude rats [6] which have immature or defective immune systems.…”

Human pathogenic hantaviruses and prevention of infection

“…54,99,100 In general, New World hantaviruses also do not induce symptoms that mirror human disease in animals. So far, only ANDV has been reported to cause HPCS-like disease in syrian hamster.…”

Hantaviruses

“…However, most of the histopathological changes noted are similar to those seen in human HPS cases. A promising model for HFRS is provided by cynomologus macaques (Macaca fascicularis) infected with PUU via the tracheal route [120]. Infected animals developed an illness clinically, immunologically and histopathologically similar to NE; however, the renal disease produced was very mild.…”