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조회553

Johns Hopkins University School of Medicine

J. Med. Virol., Jan 2024, 96 (1) | https://doi.org/10.1002/jmv.29349 Generation and characterization of a humanized ACE2 mouse model to study long-term impacts of SARS-CoV-2 infection

Chang-Yong Choi ¹, Kundlik Gadhave ², Jason Villano ³, Andrew Pekosz ⁴, Xiaobo Mao^2,5*, Hongpeng Jia^1*

¹Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

²Department of Neurology, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

³Molecular and Comparative Pathobiology, The Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

⁴Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

⁵Department of Material Science and Engineering, Johns Hopkins Whiting School of Engineering, Institute for NanoBioTechnology, Baltimore, Maryland, USA.

Chang-Yong Choi and Kundlik Gadhave contributed equally to this study.

*CORRESPONDING AUTHORS: Xiaobo Mao, Hongpeng Jia

Abstract

Although the COVID-19 pandemic has officially ended, the persistent challenge of long-COVID or post-acute COVID sequelae (PASC) continues to impact societies globally, highlighting the urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team has recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly for long-COVID/PASC research. This model exhibits human ACE2 expression in tissue and cell-specific patterns akin to mouse Ace2. When we exposed young adult hACE2ki mice (6 weeks old) to various SARS-CoV-2 lineages, including WA, Delta, and Omicron, at a dose of 5 × 10 ⁵ PFU/mouse via nasal instillation, the mice demonstrated distinctive phenotypes characterized by differences in viral load in the lung, trachea, and nasal turbinate, weight loss, and changes in pro-inflammatory cytokines and immune cell profiles in bronchoalveolar lavage fluid. Notably, no mortality was observed in this age group. Further, to assess the model's relevance for long-COVID studies, we investigated tau protein pathologies, which are linked to Alzheimer's disease, in the brains of these mice post SARS-CoV-2 infection. Our findings revealed the accumulation and longitudinal propagation of tau, confirming the potential of our hACE2ki mouse model for preclinical studies of long-COVID.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-09)
연구진국외 연구진
분야 생명과학 > 미생물학

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