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QUANTITATIVE ANALYSIS OF HOST IMMUNE FACTORS OF SARS-COV-2-INFECTED SYRIAN GOLDEN HAMSTER HAVING IMPLICATION IN THE DISEASE PATHOGENESIS AND SEVERITY
DEPARTMENT OF OTORHINOLARYNGOLOGY, SEOUL NATIONAL UNIVERSITY COLLEGE OF MEDICINE, SEOUL, KOREA
HYUN JIK KIM, HAUN SHIN, SUJI KIM, ARA JO, JINA WON, CHAN HEE GIL, CHAE-SEO RHEE
¸ñÀû: Currently, research on development of vaccines against SARS-CoV-2 is ongoing worldwide, and interest in effective therapeutics is increasing rapidly. To succeed in development of a therapeutic or vaccine against SARS-CoV-2, knowledge of the exact immune responses in vivo respiratory tract is essential. In this study, efforts were made to check the infectivity of a local SARS-CoV-2 isolate in a self- limiting and non-lethal hamster model and evaluate the differential expression of host immune responses during acute infection. ¹æ¹ý:6 week-male Syrian golden hamsters were infected with SARS-CoV-2 (BetaCoV/Korea/SNU01/2020) through intranasal inoculation. SARS-CoV-2 infection dynamics were tested using real-time PCR, immunohistochemistry and bulk-cell RNA sequencing. °á°ú:SARS-CoV-2-infected mice exhibited a significant decrease in mean body weight immediately after infection until 3 days postinfection (dpi) and recovered from 7 dpi. However, the lung-associated pathological changes were very prominent on the 4 dpi and severe pathologic findings in the lungs were noticed until 14 dpi with significantly higher histologic scores. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) in the nasal mucosa and lung tissue of SARS-CoV-2-infected hamsters at 3 dpi and interferon-stimulated genes were also induced from 3 dpi, especially neutrophil recruitment factors. IFN-lambdas were induced from 7 days after infection whereas IFN-betas were not significantly elevated in both nasal mucosa and lung tissue. When IFN-lambda (2.5ug/ml) was administered to the nose, there was no significant changes in lung pathology but the expression of inflammatory cytokines was reduced in both nasal mucosa and the lungs. °á·Ð:These findings will aid in understanding the characteristics of SARS- CoV-2 infection related with viral spread and replication in vivo respiratory tract and the potentials of IFN immune responses as a targeted therapeutic.


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