Wild-type Puumala hantavirus infection induces cytokines, C-reactive protein, creatinine, and nitric oxide in cynomolgus macaques

Hantaviruses cause two severe human diseases: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Approximately 200, 000 cases are reported annually, and there is to date no specific treatment available. A major obstacle in studying the medical aspects of HFRS and HP S has been the lack of an adequate animal model. Here we show that infectio n of cynomolgus macaques by wild-type Puumala hantavirus resulted in typica l signs of HFRS including lethargy, anorexia, proteinuria, and/or hematuria , in addition to cytokine (interleukin 6 [IL-6], IL-10, and tumor necrosis factor alpha), C-reactive protein, creatinine, and nitric oxide responses. Viral RNA was detected in plasma from days 3 to 7 postinoculation until day s 24 to 28 postinoculation, infectious virus was recovered, and the virus-s pecific immune responses (immunoglobulin M [IgM], IgG, and neutralizing ant ibodies) mimicked those seen in humans. The results indicated that the monk ey model will provide a valuable tool for studies of pathogenesis, candidat e vaccines, and antivirals for hantavirus disease.