Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells

Sano, Emi; Deguchi, Sayaka; Sakamoto, Ayaka; Mimura, Natsumi; Hirabayashi, Ai; Muramoto, Yukiko; Noda, Takeshi; Yamamoto, Takuya; Takayama, Kazuo

Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. Because iPS cells maintain the genetic information of the donor, they can be used to model individual differences in SARS-CoV-2 infection in vitro. We found that human iPS cells expressing the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) (ACE2-iPS cells) can be infected with SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ES cells from 8 individuals. Male iPS/ES cells were more capable of producing the virus compared with female iPS/ES cells. These findings suggest that ACE2-iPS cells can not only reproduce individual differences in SARS-CoV-2 infection in vitro, but they are also a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences.