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 HPS has been the lack of an adequate animal model. Here we show that infection of cynomolgus macaques by wild-type Puumala hantavirus resulted in typical 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 days 24 to 28 postinoculation, infectious virus was recovered, and the virus-specific immune responses (immunoglobulin M [IgM], IgG, and neutralizing antibodies) mimicked those seen in humans. The results indicated that the monkey model will provide a valuable tool for studies of pathogenesis, candidate vaccines, and antivirals for hantavirus disease.
Klingström
J
J
Swedish Institute for Infectious Disease Control, S-171 82 Stockholm, Sweden.
Plyusnin
A
A
Vaheri
A
A
Lundkvist
A
A
D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis*; D003404:Creatinine / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D006476:Orthohantavirus; D018778:Hantavirus Infections / Q000097:blood / Q000276:immunology*; D008252:Macaca fascicularis; D009569:Nitric Oxide / Q000097:blood*
D016207:Cytokines; D009569:Nitric Oxide; D002097:C-Reactive Protein; D003404:Creatinine