Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2

Shiu-Ju Yang,1 Ting-Chun Wei,1 Chih-Hao Hsu,1 Sin-Ni Ho,1 Chi-Yun Lai,2 Shiu-Feng Huang,2,3 Yih-Yuan Chen,4 Shih-Jen Liu,1 Guann-Yi Yu,1 Horng-Yunn Dou1,5 1National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan; 2Pathology Core L...

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Autores principales: Yang SJ, Wei TC, Hsu CH, Ho SN, Lai CY, Huang SF, Chen YY, Liu SJ, Yu GY, Dou HY
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:cbb47704206a4ca5b9beb108c462f4142021-12-02T18:50:07ZCharacterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-21178-7031https://doaj.org/article/cbb47704206a4ca5b9beb108c462f4142021-08-01T00:00:00Zhttps://www.dovepress.com/characterization-of-virus-replication-pathogenesis-and-cytokine-respon-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Shiu-Ju Yang,1 Ting-Chun Wei,1 Chih-Hao Hsu,1 Sin-Ni Ho,1 Chi-Yun Lai,2 Shiu-Feng Huang,2,3 Yih-Yuan Chen,4 Shih-Jen Liu,1 Guann-Yi Yu,1 Horng-Yunn Dou1,5 1National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan; 2Pathology Core Laboratory, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan; 3National Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan; 4Department of Biochemical Science and Technology, National Chiayi University, Chia-Yi, 60070, Taiwan; 5Department of Biological Science & Technology, National Yang Ming Chiao Tung University, Hsinchu, TaiwanCorrespondence: Horng-Yunn DouNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, 35053, TaiwanTel +886-37-206-166 ext 35529Fax +886-37-583-009Email hydou@nhri.edu.twBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus which caused a global respiratory disease pandemic beginning in December 2019. Understanding the pathogenesis of infection and the immune responses in a SARS-CoV-2-infected animal model is urgently needed for vaccine development.Methods: Syrian hamsters (Mesocricetus auratus) were intranasally inoculated with 105, 5× 105, and 106 TCID50 of SARS-CoV-2 per animal and studied for up to 14 days. Body weight, viral load and real-time PCR amplification of the SARS-CoV-2 N gene were measured. On days 3, 6 and 9, lung, blood, liver, pancreas, heart, kidney, and bone marrow were harvested and processed for pathology, viral load, and cytokine expression.Results: Body weight loss, increased viral load, immune cell infiltration, upregulated cytokine expression, viral RNA, SARS-CoV-2 nucleoprotein, and mucus were detected in the lungs, particularly on day 3 post-infection. Extremely high expression of the pro-inflammatory cytokines MIP-1 and RANTES was detected in lung tissue, as was high expression of IL-1β, IL-6, IL-12, and PD-L1. The glutamic oxalacetic transaminase/glutamic pyruvic transaminase (GOT/GPT) ratio in blood was significantly increased at 6 days post-infection, and plasma amylase and lipase levels were also elevated in infected hamsters.Conclusion: Our results provide new information on immunological cytokines and biological parameters related to the pathogenesis and immune response profile in the Syrian hamster model of SARS-CoV-2 infection.Keywords: SARS-CoV-2, hamster, immune response, pathogenesisYang SJWei TCHsu CHHo SNLai CYHuang SFChen YYLiu SJYu GYDou HYDove Medical Pressarticlesars-cov-2hamsterimmune responsepathogenesisPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 3781-3795 (2021)
institution DOAJ
collection DOAJ
language EN
topic sars-cov-2
hamster
immune response
pathogenesis
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle sars-cov-2
hamster
immune response
pathogenesis
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Yang SJ
Wei TC
Hsu CH
Ho SN
Lai CY
Huang SF
Chen YY
Liu SJ
Yu GY
Dou HY
Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2
description Shiu-Ju Yang,1 Ting-Chun Wei,1 Chih-Hao Hsu,1 Sin-Ni Ho,1 Chi-Yun Lai,2 Shiu-Feng Huang,2,3 Yih-Yuan Chen,4 Shih-Jen Liu,1 Guann-Yi Yu,1 Horng-Yunn Dou1,5 1National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan; 2Pathology Core Laboratory, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan; 3National Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli, 35053, Taiwan; 4Department of Biochemical Science and Technology, National Chiayi University, Chia-Yi, 60070, Taiwan; 5Department of Biological Science & Technology, National Yang Ming Chiao Tung University, Hsinchu, TaiwanCorrespondence: Horng-Yunn DouNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, 35053, TaiwanTel +886-37-206-166 ext 35529Fax +886-37-583-009Email hydou@nhri.edu.twBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus which caused a global respiratory disease pandemic beginning in December 2019. Understanding the pathogenesis of infection and the immune responses in a SARS-CoV-2-infected animal model is urgently needed for vaccine development.Methods: Syrian hamsters (Mesocricetus auratus) were intranasally inoculated with 105, 5× 105, and 106 TCID50 of SARS-CoV-2 per animal and studied for up to 14 days. Body weight, viral load and real-time PCR amplification of the SARS-CoV-2 N gene were measured. On days 3, 6 and 9, lung, blood, liver, pancreas, heart, kidney, and bone marrow were harvested and processed for pathology, viral load, and cytokine expression.Results: Body weight loss, increased viral load, immune cell infiltration, upregulated cytokine expression, viral RNA, SARS-CoV-2 nucleoprotein, and mucus were detected in the lungs, particularly on day 3 post-infection. Extremely high expression of the pro-inflammatory cytokines MIP-1 and RANTES was detected in lung tissue, as was high expression of IL-1β, IL-6, IL-12, and PD-L1. The glutamic oxalacetic transaminase/glutamic pyruvic transaminase (GOT/GPT) ratio in blood was significantly increased at 6 days post-infection, and plasma amylase and lipase levels were also elevated in infected hamsters.Conclusion: Our results provide new information on immunological cytokines and biological parameters related to the pathogenesis and immune response profile in the Syrian hamster model of SARS-CoV-2 infection.Keywords: SARS-CoV-2, hamster, immune response, pathogenesis
format article
author Yang SJ
Wei TC
Hsu CH
Ho SN
Lai CY
Huang SF
Chen YY
Liu SJ
Yu GY
Dou HY
author_facet Yang SJ
Wei TC
Hsu CH
Ho SN
Lai CY
Huang SF
Chen YY
Liu SJ
Yu GY
Dou HY
author_sort Yang SJ
title Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2
title_short Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2
title_full Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2
title_fullStr Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2
title_full_unstemmed Characterization of Virus Replication, Pathogenesis, and Cytokine Responses in Syrian Hamsters Inoculated with SARS-CoV-2
title_sort characterization of virus replication, pathogenesis, and cytokine responses in syrian hamsters inoculated with sars-cov-2
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/cbb47704206a4ca5b9beb108c462f414
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