Appearance of renal hemorrhage in adult mice after inoculation of patient-derived hantavirus

Background: Hemorrhagic fever with renal syndrome (HFRS) caused by hantavirus infection is characterized by fever, renal dysfunction and hemorrhage. An animal model mimicking symptoms of HFRS remains to be established. In this study, we evaluated the pathogenicity of an HFRS patient-derived Hantaan virus (HTNV) in adult mice. Methods: Five clones of HTNV strain KHF 83-61 BL (KHFV) that was derived from blood of an HFRS patient were obtained by plaque cloning. The pathogenicity of the virus clones was evaluated by using 6-week-old female BALB/c mice. Sequence analysis of the viral genome was performed by conventional methods. Results: All of the mice intravenously inoculated with KHFV clone (cl)-1, -2, -3 and -5 showed signs of disease such as transient body weight loss, ruffled fur, reduced activity and remarkably prominent hemorrhage in the renal medulla at 6 to 9 days post-inoculation (dpi) and then recovered. In contrast, mice intravenously inoculated with KHFV cl-4 did not show any signs of disease. We selected KHFV cl-5 and cl-4 as representative of high-pathogenic and low-pathogenic clones, respectively. Quantities of viral RNA in kidneys of KHFV cl-5-infected mice were larger than those in KHFV cl-4-infected mice at any time point examined (3, 6, 9 and 12 dpi). The quantities of viral RNA of KHFV cl-5 and cl-4 peaked at 3 dpi, which was before the onset of disease. Sequence analysis revealed that the amino acid at position 417 in the glycoprotein Gn was the sole difference in viral proteins between KHFV cl-5 and cl-4. The result suggests that amino acid at position 417 in Gn is related to the difference in pathogenicity between KHFV cl-5 and cl-4. When the inoculum of KHFV cl-5 was pretreated with a neutralizing antibody against HTNV strain 76-118, which belongs to the same serotype as KHFV clones, mice did not show any signs of disease, confirming that the disease was caused by KHFV infection. Conclusion: We found that an HFRS patient-derived HTNV caused renal hemorrhage in adult mice. We anticipate that this infection model will be a valuable tool for understanding the pathogenesis of HFRS

No Significant Differences Were Observed in the Amounts of DNA Strand Breaks Produced by Copper between Male and Female Liver Cells of Long-Evans Cinnamon（LEC) Strain Rats

肝炎を自然発症するLECラットの肝細胞に蓄積する銅による酸化損傷と考えられるDNA単鎖切断の量をコメット法で検出した。LECラットの肝臓では4週齢でコントロールとして用いたWKAHの30倍の銅が蓄積していた。4週齢から15週齢では雄、雌ともに週齢に依存して肝臓の銅の蓄積量は増加したが、WKAHラットでは週齢による増加は認められなかった。LECラットの肝臓でのDNA単鎖切断の量は10週齢から15週齢まで週齢に依存して急激に増加した。肝炎発症は雌が雄に比べて頻度が高いことが報告されているが、肝細胞における雌のDNA単鎖切断の量は雄に比べて大きな違いは認められなかった

Hepatic iron Accumulation Is Not Directly Associated with Induction of DNA Strand Breaks in the Liver Cells of Long-Evans Cinnamon（LEC) Rats

肝炎を自然発症するLECラットにおいてDNA単鎖切断に及ぼす銅の蓄積の影響を調べた。LECラットの肝臓において銅と鉄は4週齢から15週齢に蓄積した。低鉄食で飼育したラットでは鉄の蓄積は認められなかったが、銅の蓄積は普通食のラットと同様量認められた。肝細胞のDNA単鎖切断の量はcomet法を用いて検出した。テールが認められた細胞の頻度とテールの長さの平均値を求めたところ、低鉄食を与えたLECラットの肝細胞と普通食を与えたLECラットの間にほとんど違いは認められなかった。これらの結果からLECラットの肝細胞におけるDNA損傷の誘発には鉄の蓄積は関与していないことが示唆された

70 лет научно-исследовательскому институту охраны материнства и детства Минздрава Беларуси

НАУЧНО-ИССЛЕДОВАТЕЛЬСКИЕ ИНСТИТУТЫМАТЕРИ И РЕБЕНКА ОХРАНЫ ЗДОРОВЬЯ ЦЕНТРЫ /ИСТМЕДИЦИНСКИЕ ИНСТИТУТЫ /ИСТНАУЧНО-ИССЛЕДОВАТЕЛЬСКАЯ РАБОТАИСТОРИЯ МЕДИЦИН

Genetic Characterization of Hantaviruses Transmitted by the Korean Field Mouse (Apodemus peninsulae), Far East Russia

In an epizootiologic survey of 122 rodents captured in Vladivostok, Russia, antibodies positive for hantavirus were found in Apodemus peninsulae (4/70), A. agrarius (1/39), and Clethrionomys rufocanus (1/8). The hantavirus sequences identified in two seropositive A. peninsulae and two patients with hemorrhagic fever with renal syndrome (HFRS) from the Primorye region of Far East Russia were designated as Solovey and Primorye, respectively. The nucleotide sequences of the Solovey, Primorye, and Amur (obtained through GenBank) sequences were closely related (>92% identity). Solovey and Primorye sequences shared 84% nucleotide identity with the prototype Hantaan 76-118. Phylogenetic analysis also indicated a close relationship between Solovey, Primorye, Amur, and other viruses identified in Russia, China, and Korea. Our findings suggest that the Korean field mouse (A. peninsulae) is the reservoir for a hantavirus that causes HFRS over a vast area of east Asia, including Far East Russia

Antigenic Properties of N Protein of Hantavirus

Hantavirus causes two important rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in North and South America. Twenty-four species that represent sero- and genotypes have been registered within the genus Hantavirus by the International Committee on Taxonomy of Viruses (ICTV). Among the viral proteins, nucleocapsid (N) protein possesses an immunodominant antigen. The antigenicitiy of N protein is conserved compared with that of envelope glycoproteins. Therefore, N protein has been used for serological diagnoses and seroepidemiological studies. An understanding of the antigenic properties of N protein is important for the interpretation of results from serological tests using N antigen. N protein consists of about 430 amino acids and possesses various epitopes. The N-terminal quarter of N protein bears linear and immunodominant epitopes. However, a serotype-specific and multimerization-dependent antigenic site was found in the C-terminal half of N protein. In this paper, the structure, function, and antigenicity of N protein are reviewed

Antigenic Properties of N Protein of Hantavirus

Hantavirus causes two important rodent-borne viral zoonoses, hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome (HPS) in North and South America. Twenty-four species that represent sero- and genotypes have been registered within the genus Hantavirus by the International Committee on Taxonomy of Viruses (ICTV). Among the viral proteins, nucleocapsid (N) protein possesses an immunodominant antigen. The antigenicitiy of N protein is conserved compared with that of envelope glycoproteins. Therefore, N protein has been used for serological diagnoses and seroepidemiological studies. An understanding of the antigenic properties of N protein is important for the interpretation of results from serological tests using N antigen. N protein consists of about 430 amino acids and possesses various epitopes. The N-terminal quarter of N protein bears linear and immunodominant epitopes. However, a serotype-specific and multimerization-dependent antigenic site was found in the C-terminal half of N protein. In this paper, the structure, function, and antigenicity of N protein are reviewed