tetano
Editor, Senior Moderator
J Med Virol
. 2024 Sep;96(9):e29915.
doi: 10.1002/jmv.29915. A humanized ACE2 mouse model recapitulating age- and sex-dependent immunopathogenesis of COVID-19
Uni Park[SUP] 1 2 3 [/SUP], Jae Hoon Lee[SUP] 4 5 [/SUP], Uijin Kim[SUP] 6 [/SUP], Kyeongseok Jeon[SUP] 1 2 [/SUP], Yuri Kim[SUP] 1 2 3 [/SUP], Hyeran Kim[SUP] 1 2 [/SUP], Ju-Il Kang[SUP] 1 3 [/SUP], Mi Yeon Park[SUP] 5 [/SUP], Sun Ha Park[SUP] 5 [/SUP], Jeong Seok Cha[SUP] 6 [/SUP], Ga-Yeon Yoon[SUP] 6 [/SUP], Da-Eun Jeong[SUP] 7 [/SUP], Taehun Kim[SUP] 1 2 [/SUP], Songhyeok Oh[SUP] 1 2 [/SUP], Sang Ho Yoon[SUP] 2 8 [/SUP], Liyuan Jin[SUP] 9 [/SUP], Yoojin Ahn[SUP] 2 10 [/SUP], Min Yeong Lim[SUP] 2 10 [/SUP], Seung Ro Han[SUP] 11 [/SUP], Hye Young Kim[SUP] 2 10 [/SUP], Myoung-Hwan Kim[SUP] 2 8 12 [/SUP], Yin Hua Zhang[SUP] 8 9 [/SUP], Jun-Gu Kang[SUP] 7 [/SUP], Myung-Shin Lee[SUP] 11 [/SUP], Yoon Kyung Jeon[SUP] 13 [/SUP], Hyun-Soo Cho[SUP] 6 [/SUP], Han-Woong Lee[SUP] 4 5 [/SUP], Nam-Hyuk Cho[SUP] 1 2 3 12 13 [/SUP]
Affiliations
In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments.
Keywords: COVID‐19; Eosinophil; SARS‐CoV‐2; age; mouse model; sex.
. 2024 Sep;96(9):e29915.
doi: 10.1002/jmv.29915. A humanized ACE2 mouse model recapitulating age- and sex-dependent immunopathogenesis of COVID-19
Uni Park[SUP] 1 2 3 [/SUP], Jae Hoon Lee[SUP] 4 5 [/SUP], Uijin Kim[SUP] 6 [/SUP], Kyeongseok Jeon[SUP] 1 2 [/SUP], Yuri Kim[SUP] 1 2 3 [/SUP], Hyeran Kim[SUP] 1 2 [/SUP], Ju-Il Kang[SUP] 1 3 [/SUP], Mi Yeon Park[SUP] 5 [/SUP], Sun Ha Park[SUP] 5 [/SUP], Jeong Seok Cha[SUP] 6 [/SUP], Ga-Yeon Yoon[SUP] 6 [/SUP], Da-Eun Jeong[SUP] 7 [/SUP], Taehun Kim[SUP] 1 2 [/SUP], Songhyeok Oh[SUP] 1 2 [/SUP], Sang Ho Yoon[SUP] 2 8 [/SUP], Liyuan Jin[SUP] 9 [/SUP], Yoojin Ahn[SUP] 2 10 [/SUP], Min Yeong Lim[SUP] 2 10 [/SUP], Seung Ro Han[SUP] 11 [/SUP], Hye Young Kim[SUP] 2 10 [/SUP], Myoung-Hwan Kim[SUP] 2 8 12 [/SUP], Yin Hua Zhang[SUP] 8 9 [/SUP], Jun-Gu Kang[SUP] 7 [/SUP], Myung-Shin Lee[SUP] 11 [/SUP], Yoon Kyung Jeon[SUP] 13 [/SUP], Hyun-Soo Cho[SUP] 6 [/SUP], Han-Woong Lee[SUP] 4 5 [/SUP], Nam-Hyuk Cho[SUP] 1 2 3 12 13 [/SUP]
Affiliations
- PMID: 39279412
- DOI: 10.1002/jmv.29915
In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments.
Keywords: COVID‐19; Eosinophil; SARS‐CoV‐2; age; mouse model; sex.