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

  • Sano, Emi
    Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Deguchi, Sayaka
    Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Sakamoto, Ayaka
    Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Mimura, Natsumi
    Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Hirabayashi, Ai
    CREST, Japan Science and Technology Agency (JST); Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University
  • Muramoto, Yukiko
    CREST, Japan Science and Technology Agency (JST); Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University
  • Noda, Takeshi
    CREST, Japan Science and Technology Agency (JST); Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University
  • Yamamoto, Takuya
    Center for iPS Cell Research and Application (CiRA), Kyoto University; Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University; Medical-risk Avoidance Based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP); AMED-CREST, Japan Agency for Medical Research and Development (AMED)
  • Takayama, Kazuo
    Center for iPS Cell Research and Application (CiRA), Kyoto University

Abstract

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.

Stem cells show gender differences in COVID-19 risk. 京都大学プレスリリース. 2021-04-19.

Journal

  • iScience

    iScience 24 (5), 102428-, 2021-05

    Elsevier BV

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