• 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.

• 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.

• 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.

• 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.

• Toxicological Research
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• v.13 no.1_2
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• pp.157-160
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• 1997

The primary skin and eye irritancy of the combined vaccine (KGCC-95VI) for the prophylaxis against Japanese encephalitis and Hantaan virus infection recently developed by Korea Green Cross Corporation was investigated. The KGCC-95VI was applied to the back skins of the New Zealand White rabbits. The rabbits were observed for 72 hours and did not exhibit erythema, eschar and edema. The eyes of the rabbits were exposed to the KGCC-95VI. The rabbits were observed for 7 days and did not exhibit any ocular findings on cornea, iris and conjuntivae. The KGCC-95VI is considered not to have the primary skin and eye toxicity in rabbits.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.174-178
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• 1997

The immnunogenicity of the possible non-essential component of the combined vaccine (KGCC-957) for the prophylaxis against Japanese encephalitis and Hantaan virus infection recently developed by Korea Green Cross Corporation was investigated using the Hartley guinea pigs. The KGCC-95Vl was administered to the guinea pigs subcutaneously to sensitize the animals. The guinea pigs did not induce any anaphylactic immune responses which could be detectable by the active systemic anaphylaxis (ASA), the passive systemic anaphylaxis (PSA), and the passive cutaneous anaphylaxis (PCA) tests. The KGCC-95Vl is considered not to induce any anaphylactic immune responses except the prophylatic immune effects of the vaccine.

• 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.28 no.3
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• pp.287-293
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• 1998

Hantaan virus are widely distributed in rodents populations in Korea. Two antigenically distinct hantaviruses have been isolated from Apodemus agrarius in 1976 and Rattus norvegicus in 1980 in Korea. This study was designed to find the serological evidence of hantavirus infection among indigenous wild rodents captured in 7 Mountains located in Kangwon province of south Korea. A total 191 wild rodents of 3 species were trapped in Chumbong mountain, Kali mountain, Hansuk mounatin, Chachil peak, Bukam ridge, Kyebang mountain and Odae mountain in 1997. Serologic evidence for hantavirus infection were tested using hantavirus antigens by indirect immunofluorescent antibody technique (IFA). Among 85 Apodemus agrarius, 77 Apodemus peninsulae and 29 Eothenomys regulus; 8 A. agrarius (9.4%), 11 A. peninsulae (14.3%) and 4 E. regulus (13.8%) were immunofluorescent antibody positive against hantaan virus. IF antibody titers against Puumala virus of 3 E. regulus sera were higher than against hantaan virus. This data suggest that several antigenically distinct hantaviruses have been circulated in rodent populations in Korea.

• Toxicological Research
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• v.13 no.3
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• pp.275-279
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• 1997

The acute toxicity of the combined vaccine (KGCC-95VI) for the prophylaxis against Japanese encephalitis and Hantaan virus infection. recently developed by Korea Green Cross Corporation, was investigated. KGCC-95VI was administered to the Balb /c mice in two routes, orally and subcutaneously, and into the New Zealand White rabbits subcutaneously. $LD_{50}$ was not accessible as there were no deaths in the group treated even at a dose 800 times the expected clinical dose in both animal species. Between the treated and control groups there were no statistically significant differences in body weight changes and clinical signs during the 14-day observation period, and no pathological gross findings. Accordingly KGCC-95VI is considered not to have the acute toxicity in mice and rabbits.

• Toxicological Research
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• v.13 no.4
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• pp.353-357
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• 1997

The possibility of the allergic encephalomyelitis caused by the combined vaccine (KGCC95VI) for the prophylaxis against Japanese encephalitis and Hantaan virus infection, recently developed by Korea Green Cross Corporation, was investigated in the Hartley guinea pigs. The KGCC-95VI was administered to the guinea pigs subcutaneously to sensitize the animals three times at one month intervals. There were no clinical signs or gross pathological findings. There were no abnormal histopathological findings at cerebrums, cerebellums, brain stems and the spinal cords. The concentration of myelin basic protein was 1.10 ng/dose quantified by ELISA, which met the guide4ine of below 2 ng/ml/dose recommended by American Society of Health -System Pharmacists(AHPS) Drug Information. Accordingly, the KGCC-95VI is considered not to induce any allergic immune responses which may lead to the experimental allergic encephalomyelitis.