title: Infection of Hantaan virus strain AA57 leading to pulmonary disease in laboratory mice.
abstract: Hantaan virus (HTNV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). The pathogenesis of HFRS has not been fully elucidated, mainly due to the lack of a suitable animal model. In laboratory mice, HTNV causes encephalitis. However, that symptom is dissimilar to human hantavirus infections. We found that HTNV strain AA57 (isolated from Apodemus agrarius in Far East Russia) caused pulmonary disease in 2-week-old ICR mice. The clinical signs of the infected mice were piloerection, trembling, hunching, labored breathing, and body-weight loss. A large volume of pleural effusion was collected from thoracic cavities of the dead mice. Overall, 45% of the mice inoculated with 3000 focus forming units (FFU) of the virus began to show clinical symptoms at 8 days post-inoculation, and 25% of the inoculated mice died within 3 days of onset of the disease. The morbidity and mortality rates of the mice inoculated with 30-30,000FFU of HTNV strain AA57 were roughly equivalent. The highest rates of virus positivity (11/12) and the highest titers of HTNV strain AA57 were detected in the lungs of the dead mice, while lower detection rates and viral titers were found in the heart, kidneys, spleen, and brain. Interstitial pneumonia, perivascular edema, hemorrhage, inflammatory infiltration and vascular failure were observed in the lungs of the sick mice. Hantaviral antigens were detected in the lung endothelial cells of the sick mice. The symptoms and pathology of this mouse model resemble those of hantavirus pulmonary syndrome (HPS) and, to a certain extent, those of HFRS. This is the first report that, in laboratory mice, the HFRS-related hantavirus causes a HPS-like disease and shares some symptom similarities with HFRS.
authors: Laboratory of Public Health, Graduate School of Veterinary Medicine, Hokkaido University, Kita-18, Nishi-9, Sapporo 060-0818, Japan.
authors: Takahiro
authors: T
authors: Seto
authors: Noriyo
authors: N
authors: Nagata
authors: Keisuke
authors: K
authors: Yoshikawa
authors: Osamu
authors: O
authors: Ichii
authors: Takahiro
authors: T
authors: Sanada
authors: Ngonda
authors: N
authors: Saasa
authors: Yuka
authors: Y
authors: Ozaki
authors: Yasunori
authors: Y
authors: Kon
authors: Kentaro
authors: K
authors: Yoshii
authors: Ikuo
authors: I
authors: Takashima
authors: Hiroaki
authors: H
authors: Kariwa
mesh_terms: D000825:Animal Structures / Q000473:pathology / Q000821:virology; D000818:Animals; D004195:Disease Models, Animal; D005202:Asia, Eastern; D005260:Female; D018063:Hantaan virus / Q000302:isolation & purification / Q000472:pathogenicity*; D008171:Lung Diseases / Q000473:pathology* / Q000821:virology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051189:Murinae / Q000821:virology; D012426:Russia; D016019:Survival Analysis