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

Abstract

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 [phone] ext 35529Fax [phone]Email [email protected]: 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

Keywords

• sars-cov-2
• hamster
• immune response
• pathogenesis