Comparison of infection and human immune responses of two SARS-CoV-2 strains in a humanized hACE2 NIKO mouse model

人源化 hACE2 NIKO 小鼠模型中两种 SARS-CoV-2 毒株的感染和人体免疫反应比较

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作者:Kylie Su Mei Yong #, Danielle E Anderson #, Adrian Kang Eng Zheng, Min Liu, Sue Yee Tan, Wilson Wei Sheng Tan, Qingfeng Chen, Lin-Fa Wang

Abstract

The COVID-19 pandemic has sickened millions, cost lives and has devastated the global economy. Various animal models for experimental infection with SARS-CoV-2 have played a key role in many aspects of COVID-19 research. Here, we describe a humanized hACE2 (adenovirus expressing hACE2) NOD-SCID IL2Rγ-/- (NIKO) mouse model and compare infection with ancestral and mutant (SARS-CoV-2-∆382) strains of SARS-CoV-2. Immune cell infiltration, inflammation, lung damage and pro-inflammatory cytokines and chemokines was observed in humanized hACE2 NIKO mice. Humanized hACE2 NIKO mice infected with the ancestral and mutant SARS-CoV-2 strain had lung inflammation and production of pro-inflammatory cytokines and chemokines. This model can aid in examining the pathological basis of SARS-CoV-2 infection in a human immune environment and evaluation of therapeutic interventions.

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