Background: To deal with SARS-CoV-2 variants, the development of various vaccines and anti-viral drugs requires proper models for reliable evaluation. However, so far there is no in vivo model to study the infection of virus into human lung tissue.
Aim: We aim to generate humanized mouse lung model by intra-pulmonary transplantation of human P63+ lung progenitor cells and then test whether the SARS-CoV-2 could infect the lung.
Methods: Human P63+ lung progenitor cells, isolated from healthy donors or patients, were intratracheally transplanted into the pre-conditioned mouse lung, which were then infected with SARS-CoV-2 pseudo or authentic virus.
Results: Transplanted human cells successfully engrafted into mouse lung and reconstituted the human lung epithelium, some of which could give rise to air sac-like structure gradually, maintained the incorporation for more than one month. All cells isolated from either healthy or patient donors, could generate mouse-human chimeric lung. Approximately 5-12 % of human cells expressed physiological level of SARS-CoV-2 receptor ACE2, which was variable between individual persons. After pseudovirus infection, significant infection signal as visualized by the pseudovirus-encoded GFP expression in chimeric lobe. After authentic virus infection, quantitative PCR and immunostaining detected the expression of viral nucleocapsid protein in chimeric lobe.
Conclusion:Although with a relatively low infection efficiency, the humanized mouse lung could indeed be infected by SARS-CoV-2. This conceptional work enables us to study the SARS-Cov-2 infection in lung with physiological level of ACE2 expression in human cells.