SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) Variants Induce Pathogenic Patterns in K18-hACE2 Transgenic Mice Distinct from Early Strains

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Nov 13

PMID 34772941

Citations 55

Authors

Peter Radvak

Hyung-Joon Kwon

Martina Kosikova

Uriel Ortega-Rodriguez

Ruoxuan Xiang

Je-Nie Phue

Rong-Fong Shen

James Rozzelle

Neeraj Kapoor

Taylor Rabara

Jeff Fairman

Hang Xie

Affiliations

Soon will be listed here.

Abstract

SARS-CoV-2 variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta) show increased transmissibility and enhanced antibody neutralization resistance. Here we demonstrate in K18-hACE2 transgenic mice that B.1.1.7 and B.1.351 are 100-fold more lethal than the original SARS-CoV-2 bearing 614D. B.1.1.7 and B.1.351 cause more severe organ lesions in K18-hACE2 mice than early SARS-CoV-2 strains bearing 614D or 614G, with B.1.1.7 and B.1.351 infection resulting in distinct tissue-specific cytokine signatures, significant D-dimer depositions in vital organs and less pulmonary hypoxia signaling before death. However, K18-hACE2 mice with prior infection of early SARS-CoV-2 strains or intramuscular immunization of viral spike or receptor binding domain are resistant to the lethal reinfection of B.1.1.7 or B.1.351, despite having reduced neutralization titers against these VOC than early strains. Our results thus distinguish pathogenic patterns in K18-hACE2 mice caused by B.1.1.7 and B.1.351 infection from those induced by early SARS-CoV-2 strains, and help inform potential medical interventions for combating COVID-19.

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