RT Journal Article
SR Electronic
T1 Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.22.432218
DO 10.1101/2021.02.22.432218
A1 Emi Sano
A1 Ayaka Sakamoto
A1 Natsumi Mimura
A1 Ai Hirabayashi
A1 Yukiko Muramoto
A1 Takeshi Noda
A1 Takuya Yamamoto
A1 Kazuo Takayama
YR 2021
UL http://biorxiv.org/content/early/2021/02/22/2021.02.22.432218.abstract
AB Genetic differences are a primary reason for differences in the susceptibility and severity of coronavirus disease 2019 (COVID-19). Because induced pluripotent stem (iPS) cells maintain the genetic information of the donor, they can be used to model individual differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro. Notably, undifferentiated human iPS cells themselves cannot be infected bySARS-CoV-2. Using adenovirus vectors, here 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, the budding of viral particles, the production of progeny virus, double membrane spherules, and double-membrane vesicles were confirmed. We also evaluated COVID-19 therapeutic drugs in ACE2-iPS cells and confirmed the strong antiviral effects of Remdesivir, EIDD-2801, and interferon-beta. In addition, 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 as 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.Competing Interest StatementThe authors have declared no competing interest.