PT  - JOURNAL ARTICLE
AU  - Peter Radvak
AU  - Hyung Joon Kwon
AU  - Martina Kosikova
AU  - Uriel Ortega-Rodriguez
AU  - Ruoxuan Xiang
AU  - Je-Nie Phue
AU  - Rong-Fong Shen
AU  - James Rozzelle
AU  - Neeraj Kapoor
AU  - Taylor Rabara
AU  - Jeff Fairman
AU  - Hang Xie
TI  - B.1.1.7 and B.1.351 variants are highly virulent in K18-ACE2 transgenic mice and show different pathogenic patterns from early SARS-CoV-2 strains
AID  - 10.1101/2021.06.05.447221
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.05.447221
4099  - http://biorxiv.org/content/early/2021/06/07/2021.06.05.447221.short
4100  - http://biorxiv.org/content/early/2021/06/07/2021.06.05.447221.full
AB  - SARS-CoV-2 continues to circulate globally resulting in emergence of several variants of concern (VOC), including B.1.1.7 and B.1.351 that show increased transmissibility and enhanced resistance to antibody neutralization. In a K18-hACE2 transgenic mouse model, we demonstrate that Both B.1.1.7 and B.1.351 are 100 times more lethal than the original SARS-CoV-2 bearing 614D. Mice infected with B.1.1.7 and B.1.351 exhibited more severe lesions in internal organs than those infected with early SARS-CoV-2 strains bearing 614D or 614G. Infection of B.1.1.7 and B.1.351 also results in distinct tissue-specific cytokine signatures, significant D-dimer depositions in vital organs and less pulmonary hypoxia signaling before death as compared to the mice infected with early SARS-CoV-2 strains. However, K18-hACE2 mice with the pre-existing immunity from prior infection or immunization were resistant to the lethal reinfection of B.1.1.7 or B.1.351, despite having reduced neutralization titers against these VOC. Our study reveals distinguishing pathogenic patterns of B.1.1.7 and B.1.351 variants from those early SARS-CoV-2 strains in K18-hACE2 mice, which will help to inform potential medical interventions for combatting COVID-19.Competing Interest StatementThe authors have declared no competing interest.