Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells
Emi Sano,
Sayaka Deguchi,
Ayaka Sakamoto,
Natsumi Mimura,
Ai Hirabayashi,
Yukiko Muramoto,
Takeshi Noda,
Takuya Yamamoto,
Kazuo Takayama
Affiliations
Emi Sano
Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan
Sayaka Deguchi
Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan
Ayaka Sakamoto
Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan
Natsumi Mimura
Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan
Ai Hirabayashi
Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; CREST, Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan
Yukiko Muramoto
Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; CREST, Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan
Takeshi Noda
Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; CREST, Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan
Takuya Yamamoto
Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501 Japan; Medical-risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto 606-8507, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo 100-0004, Japan
Kazuo Takayama
Center for iPS Cell Research and Application (CiRA), Kyoto University, Shogoin Kawaharacho 53, Sakyo-ku, Kyoto 606-8507, Japan; Corresponding author
Summary: 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.
