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

Genetic differences are a primary reason for differences in the susceptibility and severity of COVID-19. As induced pluripotent stem (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 w SARS-CoV-2. In infected ACE2-iPS cells, the expression of SARS-CoV-2 nucleocapsid protein, budding of viral particles, and production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We performed SARS-CoV-2 infection experiments on ACE2-iPS/ embryonic stem (ES) cells from eight 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 also are a useful resource to clarify the causes of individual differences in COVID-19 due to genetic differences. © 2021 The Author(s).

Citation

Emi Sano, Sayaka Deguchi, Ayaka Sakamoto, Natsumi Mimura, Ai Hirabayashi, Yukiko Muramoto, Takeshi Noda, Takuya Yamamoto, Kazuo Takayama. Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells. iScience. 2021 May 21;24(5):102428

PMID: 33880436

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