• The Journal of Korean Society of Virology
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• v.28 no.4
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• pp.317-325
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• 1998

The primary culture of human nasal epithelial cells was performed using the inferior nasal turbinate tissues, and infected with Hantaan virus to examine the hypothesis of airborne transmission of Hantaan virus in humans. The primary culture cells were identified as epithelial cells by morphologic and immunologic analyses. The viral antigens were detected in the primary human nasal epithelial cells infected with Hantaan virus by immunofluorescence staining. The ICAM-1 induction by Hantaan virus or $IFN-{\gamma}$ was examined in the primary human nasal epithelial cells and human lung fibroblasts (WI-38). Hantaan virus induced the surface ICAM-1 in WI-38 cells in a time-dependent manner, and $IFN-{\gamma}$ induced the surface ICAM-1 in a dose-dependent manner in HNEC and WI-38 cells. These results revealed that the human nasal epithelial cells are susceptible to Hantaan viral infection supporting the hypothesis of airborne transmission of Hantaan virus in humans. The human lung fibroblasts also might have an important role in the pathogenesis of Hantaan virus through the induction of ICAM-1.

• The Journal of Korean Society of Virology
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• v.28 no.2
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• pp.147-155
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• 1998

Hantavirus is a genus of the Bunyaviridae family consisting following serotype groups: Hantaan, Seoul, Puumala, Prospect Hill, Thailand, Belgrade, Thotta palayam, Sin Nombre. Most of Hantavirus group have been associated with many clinically similar disease known collectively as hemorrhagic fever with renal syndrome (HFRS). Hantaan virus is the prototype of the genus hantavirus, originally isolated from Apodemus agrarius. Bat was found as a natural host for Hantaan virus in Lee's lab for the first time. Then, Hantaan-like virus was isolated Hantaan-like virus from bat. To identify hantaviruses that are present in Korea among bats, bats were collected from Jeong-Sun, Won-Joo, Chung-Ju and Hwa-Cheon area, RNA was isolated from lung and serum. RT-PCR was performed with a universal primer from M segment. Nested RT-PCR was carried out to differentiate Hantaan, Seoul and Puumala virus using serotype specific primers. As we expected, Hantaan viruses were detected in bats and Seoul virus was not detected. Interestingly, Puumala viruses were also detected in bats from Won-Ju, but not in other areas. Puumala virus is originally isolated from Clethrinomys glareolus, and cause light HFRS. Recently, Paradoxomis webbiana, a wild bird turn out to be a reservoir for Puumala virus in Korea. These data indicate that bat is a new natural reservoir of Puumala virus.

• The Journal of Korean Society of Virology
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• v.26 no.2
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• pp.245-249
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• 1996

Hantaan virus vaccine was developed in 1988 and proved effective. This vaccine is a kind of inactivated vaccine, stable for two years when stored at $2-8^{\circ}C$. Almost virus vaccines including Hantaan virus vaccine are produced and kept in fluid state, and the immumogenicity can be easily destroyed at room temperature or at higher temperature. Therefore the vaccines should be kept in the refrigerator to maintain the immunogenicity. In this study, glucose and/or lactose was added as a stabilizer into Hantaan virus vaccine to increase the stability and dried in vaccum with ethanol treatment. 5% glucose and or lactose in Hantaan virus vaccine most effectively increased the stability of vaccine and maintained the immunogenicity at least for three months at room temperature. But drying with ethanol treatment did not help increasing the stability. These results suggest that glucose and lactose could be good stabilizer of virus vaccines.

• The Journal of the Korean Society for Microbiology
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• v.21 no.2
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• pp.227-231
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• 1986

The hemagglutination activities of Hantaan virus and Seoul virus were demonstrated. The hemagglutinins were prepared by sucrose-acetone extraction method from suckling mouse brains infectecd with Hantaan and Seoul viruses. Hemagglutination of goose erythrocytes by these viral hemagglutinins was pH dependent in phosphate buffer system. Hantaan and Seoul viruses were distinguished by pH range of hemagglutination. 76/118 and 79/90 strains of Hantaan virus showed hemagglutination at the range of pH 5.75-6.4 and the optimal pH was 5.75 with the titer of 1:512 in 76/118 and 1:256 in 79/90. In contrast, KSNUSD 84/34 strain of Seoul virus revealed hemagglutination at the range of pH 6.2-6.4 and the optimal pH was 6.4 with the titer of 1 : 64.

• Journal of Microbiology and Biotechnology
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• v.12 no.6
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• pp.882-889
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• 2002

Hantaan vims production, using human immortalized retina cell (PER. C6), was investigated to develop an inactivated virus vaccine. To infect Hantaan virus into PER. C6, two infection methods (medium-to-cell and cell-to-cell) were tried, and IFA results showed that the cell-to-cell infection method was very useful for producing Hantaan virus-infected PER, C6. Hantaan virus production was significantly affected by the growth rate of PER. C6 and the content of FBS in medium. Higher specific growth rate of infected PER. C6 and lower FBS content induced higher production of Hantaan virus. The inactivated human cell-culture vaccines with various EIA titers were prepared, their antibody responses were compared with those of inactivated suckling mouse brain vaccines ($Hantavax^처리불가$). and the result showed their immunogenicities were slightly higher than those of inactivated suckling mouse vaccines. Therefore, this study shows the possibility of the development of Hantaan virus vaccine from a human cell culture.

• Korean Journal of Veterinary Research
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• v.34 no.1
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• pp.147-152
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• 1994

Eleven shrews were caught from three areas of Korea. All of them were confirmed in the same species, Crocidura lasiura. All of sera from wild shrews were examined by indirect immunofluorescent test against Hantaan-related virus. The antibody to Hantaan-related virus was detected by 2 out of 11 shrews. Just 2 of 7 shrews from BG area were sero-positive for Hantaan-related virus antigen and none from other. All of sero-positive for Hantaan-related virus antigen belonged to male with antibody titer of 1:40 to 1:80. Two Hantaan-related viruses were isolated in vivo and in vitro.

• Korean Journal of Microbiology
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• v.30 no.2
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• pp.124-128
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• 1992

A total of 275 wild hats captured in Korea here examined 011 the possibility that they will harhor and spread the inkctious pathog.cns of Hantaan virus and Rickettsia. They possessed ontihotlies in 3.6'K) blood sera against Hantaan virus by the indirect in~~nunofluoresccnctec hnique and showed relatively high serum titers with a range of 16 to 1014X. whereus 13.7\ulcorner0 of them were positive to Rickettsia. dividing into 3.3% against R. ~.sur,~ugc~rnusllr.Ri.1 k, against R. siht)ric.n tick ~vphus,a nd 4.4% against R. thai tick pphus. respectively. 11 was first confirmed in Korean wild hats that arc infccted with Hantaan virus and Rickettsia agents. and play a role as vector.

• Korean Journal of Veterinary Research
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• v.33 no.2
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• pp.321-326
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• 1993

Sixty eight wild rats were caught from Seoul, Kyonggi, Kangwon, Cholla, and Kyongsang provinces in Korea. All of them were confirmed in the same species, Rattus norvigicus. All of sera from wild rats were examined by indirect immunofluorescent test against Hantaan-related virus. Detection of anti-body to Hantaan-related virus were 4 out of 68 rats(5.9%), including 2 of 8(25.0%) rats in Kangwon and 2 of 20 rats(10.0%) in Kyongsang province. No difference of the sero-positive rates between sex of rats tested to Hantaan-related virus was recognized. According to age, four rats with antibodies(1:320~640) to Hantaan-related virus belonged one subadult, one young adult, one middle aged adult, and one old adult, respectively.

• The Journal of Korean Society of Virology
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• v.26 no.1
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• pp.47-58
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• 1996

Histopathological vascular changes in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus include increased vascular permeability, disseminated intravascular coagulation, thrombocytopenia and changes in coagulation activity. Although vascular endothelial cells of main target organs such as kidney infected with Hantaan virus are not damaged but swelling of endothelial cells, perivascular exudates and infiltration of mononuclear cells and fresh interstitial hemorrhages are common. However, the pathogenesis of cell infiltration and hemorrhages around vascular endothelial cells are not well understood. Some endothelial cell molecules or vascular adhesins that acts as adhesion moleulces for leukocyte are expressed on endothelial cells close to site of inflammation. However, whether the expression of endothelial adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule (ELAM) on vascular endothelial cells are increased by infection with Hantaan virus has not been studied. In this study, the relationship between the expression of VCAM-1, ICAM-1 and ELAM and adhesion of mononuclear cells on endothelial cells of human blood vessels infected with Hantaan virus was investigated. The endothelial cells of umbilical vein was passaged three times in culture medium and the monolayered cells were infected with $10^5\;pfu/ml$ of Hantaan virus grown in Vera E6 cell cultures. The multiplication of virus in cultured endothelial cells was monitored by immunohistochemistry and the expression of adhesion molecules was demonstrated by immunohistochemistry using monoclonal antibodies against VCAM-1, ICAM-1 and ELAM. And in situ hybriditation against ICAM-1 was also performed. The endothelial adhesion molecules, VCAM and ICAM, were expressed after 6 hours postinfection, respectively, and their expressions lasted for 72 hours. Similar expression of VCAM and ICAM appeared on endothelial cells by infection with virus, but the expression of ELAM was not recognized up to 72 hours postinfection. Microscopically, it was noted that many monocuclear cells adhered on endothelial cells infected with viruses. In an electronmicroscopic study, the transendothelial migration of mononuclear cells was observed on monolayered endothelial cells infected with virus. This results suggested that the endothelial adhesion molecules, particulary VCAM and ICAM, might be expressed on endothelial cells by infection with Hantaan virus and these molecules play a key role in the adhesion and extravasation of inflammatory cells around blood vessels.

• The Journal of Korean Society of Virology
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• v.29 no.4
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• pp.211-219
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• 1999

Most of the currently licensed viral and bacterial vaccines produced in the world are in state of antigen suspension and the immunogenicity of vaccines could be maintained for one or two years only by keeping in the refrigerator, but without refrigeration vaccines would easily lose their immunogenicites. In this study, as a step to develope the method of increasing the stability of vaccines and maintaining the immunogenicity of vaccines for a long time at room temperature or higher temperature, trehalose, glucose and lactose at different concentration were added into the Hantaan virus vaccines and then kept at $37^{\circ}C$ for 12, 24, 48 hours and at room temperature for seven days respectively. Treated vaccines were then inoculated respectively into ICR mice and the titers of antibody against the antigen of Hantaan virus from the mice sera were evaluated. Vaccine without sugar lost immunogenicity completely in 24 hour at $37^{\circ}C$, but the vaccines containing trehalose could maintain some of the immunogenicity even after exposure at $37^{\circ}C$ for 48 hours and the best concentration of trehalose for maintaining the immunogenicities of vaccines was $7.5{\sim}10$ percent. The results suggest that addition of trehalose could increase the stability of Hantaan virus vaccine.