Urinalysis of a Hantaan virus-infected mouse model of hemorrhagic fever with renal syndrome

Abstract

Hantaan virus causes hemorrhagic fever with renal syndrome (HFRS), a rodent-borne zoonotic disease. Korean hemorrhagic fever virus (KHFV), a strain of Hantaan virus, showed symptoms in mice similar to those of HFRS patients, including weight loss, renal medullary hemorrhage, hepatitis, and neutrophilia. Therefore, mice inoculated with KHFV were expected to serve as a model for HFRS. However, urinary symptoms characteristic of HFRS, such as proteinuria and hematuria, have not yet been examined. In this study, we attempted to evaluate renal function by analyzing urine. As a result, in mice inoculated with KHFV, oliguria and hematuria accompanied by weight loss were observed at 5–8 days after inoculation, and albuminuria was also observed. In addition, the viral load in the kidney and viral excretion into the urine were observed. When the neutralizing monoclonal antibody HCO2 against Hantaan virus was administered before inoculation, all symptoms were abolished. To clarify the therapeutic effect of HCO2 antibody, it was administered intravenously on days 1, 3, and 5 after infection. Weight loss and renal medullary hemorrhage were suppressed, and histological examination revealed micro renal hemorrhage in mice on day 5 administration. It was found that neutralizing antibody can be expected to alleviate symptoms even if it is administered late, and that early administration is more effective. These results indicate that this mouse model shows symptoms like human HFRS and can be used to evaluate antiviral effects.