tetano
Editor, Senior Moderator
J Gen Virol
. 2025 Sep;106(9).
doi: 10.1099/jgv.0.002148. Susceptibility of different mouse strains to SARS-CoV-2 spike receptor-binding domain protein-induced lung inflammation: a comparative study
Yujeong Ha[SUP] 1 2 [/SUP], Young Hyun Lee[SUP] 1 2 [/SUP], Hyo-Sung Jo[SUP] 1 2 [/SUP], Tae Woo Kwon[SUP] 1 2 [/SUP], Yujin Seo[SUP] 1 2 [/SUP], Dong Woon Kim[SUP] 3 [/SUP], Ik-Hyun Cho[SUP] 1 2 4 5 [/SUP]
Affiliations
Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) are widely used in research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to their susceptibility to viral infection. However, the extent to which genetic differences among mouse strains affect inflammatory responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein remains unclear. In this study, we compared the susceptibility of five commonly used mouse strains - DBA2, ICR, C3H/HeOuJ, BALB/c and C57BL/6J - to RBD-induced pulmonary inflammation. Histopathological analysis revealed that DBA2 and C57BL/6J mice exhibited significantly heightened inflammatory responses, characterized by increased angiotensin-converting enzyme 2 (ACE2) expression, macrophage infiltration, upregulation of proinflammatory cytokines (e.g. IL-1β, TNF-α) and activation of the IL-6/STAT3 and nicotinamide adenine dinucleotide phosphate oxidase pathways. These responses were markedly attenuated by pretreatment with an anti-ACE2 antibody, supporting a potential role of RBD-ACE2 interactions in driving inflammation, although ACE2-independent mechanisms cannot be excluded. Our findings suggest that DBA2 and C57BL/6J mice are particularly sensitive to RBD exposure and represent cost-effective and physiologically relevant models for studying ACE2-mediated lung inflammation and for evaluating therapeutic interventions targeting coronavirus disease 2019-related inflammatory mechanisms.
Keywords: ACE2; SARS-CoV-2; lung inflammation; mouse strain; receptor-binding domain.
. 2025 Sep;106(9).
doi: 10.1099/jgv.0.002148. Susceptibility of different mouse strains to SARS-CoV-2 spike receptor-binding domain protein-induced lung inflammation: a comparative study
Yujeong Ha[SUP] 1 2 [/SUP], Young Hyun Lee[SUP] 1 2 [/SUP], Hyo-Sung Jo[SUP] 1 2 [/SUP], Tae Woo Kwon[SUP] 1 2 [/SUP], Yujin Seo[SUP] 1 2 [/SUP], Dong Woon Kim[SUP] 3 [/SUP], Ik-Hyun Cho[SUP] 1 2 4 5 [/SUP]
Affiliations
- PMID: 40982317
- DOI: 10.1099/jgv.0.002148
Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) are widely used in research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to their susceptibility to viral infection. However, the extent to which genetic differences among mouse strains affect inflammatory responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein remains unclear. In this study, we compared the susceptibility of five commonly used mouse strains - DBA2, ICR, C3H/HeOuJ, BALB/c and C57BL/6J - to RBD-induced pulmonary inflammation. Histopathological analysis revealed that DBA2 and C57BL/6J mice exhibited significantly heightened inflammatory responses, characterized by increased angiotensin-converting enzyme 2 (ACE2) expression, macrophage infiltration, upregulation of proinflammatory cytokines (e.g. IL-1β, TNF-α) and activation of the IL-6/STAT3 and nicotinamide adenine dinucleotide phosphate oxidase pathways. These responses were markedly attenuated by pretreatment with an anti-ACE2 antibody, supporting a potential role of RBD-ACE2 interactions in driving inflammation, although ACE2-independent mechanisms cannot be excluded. Our findings suggest that DBA2 and C57BL/6J mice are particularly sensitive to RBD exposure and represent cost-effective and physiologically relevant models for studying ACE2-mediated lung inflammation and for evaluating therapeutic interventions targeting coronavirus disease 2019-related inflammatory mechanisms.
Keywords: ACE2; SARS-CoV-2; lung inflammation; mouse strain; receptor-binding domain.