Abortive infection of bat fibroblasts with SARS-CoV-2

Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat ( ) pluripotent cells and fibroblas...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2024-10, Vol.121 (43), p.e2406773121
Hauptverfasser: Bisht, Punam, Gallagher, Michael D, Barrasa, M Inmaculada, Boucau, Julie, Harding, Alfred, Déjosez, Marion, Godoy-Parejo, Carlos, Bisher, Margaret E, de Nola, Giovanni, Lytton-Jean, Abigail K R, Gehrke, Lee, Zwaka, Thomas P, Jaenisch, Rudolf
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container_issue 43
container_start_page e2406773121
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 121
creator Bisht, Punam
Gallagher, Michael D
Barrasa, M Inmaculada
Boucau, Julie
Harding, Alfred
Déjosez, Marion
Godoy-Parejo, Carlos
Bisher, Margaret E
de Nola, Giovanni
Lytton-Jean, Abigail K R
Gehrke, Lee
Zwaka, Thomas P
Jaenisch, Rudolf
description Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat ( ) pluripotent cells and fibroblasts. Since bat cells do not express an angiotensin-converting enzyme 2 (ACE2) receptor that allows virus infection, we transduced the human ACE2 (hA) receptor into the cells and found that transduced cells can be infected with SARS-CoV-2. Compared to human embryonic stem cells-hA, infected bat induced Pluripotent Stem Cells (iPSCs)-hA produced about a 100-fold lower level of infectious virus and displayed lower toxicity. In contrast, bat embryonic fibroblast-hA produced no infectious virus while being infectable and synthesizing viral RNA and proteins, suggesting abortive infection. Indeed, electron microscopy failed to detect virus-like particles in infected bat fibroblasts in contrast to bat iPSCs or human cells, consistent with the latter producing infectious viruses. This suggests that bat somatic but not pluripotent cells have an effective mechanism to control virus replication. Consistent with previous results by others, we find that bat cells have a constitutively activated innate immune system, which might limit SARS-CoV-2 infection compared to human cells.
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subjects ACE2
Angiotensin
Angiotensin-converting enzyme 2
Angiotensin-Converting Enzyme 2 - genetics
Angiotensin-Converting Enzyme 2 - metabolism
Animals
Biological Sciences
Chiroptera - virology
Coronaviruses
COVID-19
COVID-19 - immunology
COVID-19 - virology
Electron microscopy
Embryo cells
Embryo fibroblasts
Fibroblasts
Fibroblasts - metabolism
Fibroblasts - virology
Humans
Immune system
Immunological tolerance
Induced Pluripotent Stem Cells - metabolism
Induced Pluripotent Stem Cells - virology
Infections
Innate immunity
Peptidyl-dipeptidase A
Pluripotency
Receptors
Respiratory diseases
Rhinolophus ferrumequinum
RNA viruses
SARS-CoV-2 - immunology
SARS-CoV-2 - physiology
Severe acute respiratory syndrome coronavirus 2
Stem cells
Toxicity
Viral diseases
Viral infections
Virus Replication
Virus-like particles
Viruses
title Abortive infection of bat fibroblasts with SARS-CoV-2
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