Abortive infection of bat fibroblasts with SARS- CoV-2

• 成果类型: Article
• 署名作者: Bisht, Punam; Gallagher, Michael D.; Barrasa, M. Inmaculada; Boucau, Julie; Harding, Alfred; Dejosez, Marion; Parejo, Carlos Godoy -; Bisher, Margaret E.; de Nola, Giovanni; Lytton-Jean, Abigail K. R.; Gehrke, Lee; Zwaka, Thomas P.; Jaenisch, Rudolf
• 署名单位: Massachusetts Institute of Technology (MIT); Whitehead Institute; Harvard University; Massachusetts Institute of Technology (MIT); Ragon Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9280
• DOI: 10.1073/pnas.2406773121
• 发表日期: 2024-10-22
• 关键词: expression; resistance; immunity; genomes; virus; cells

摘要

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 ( Rhinolophus ferrumequinum) 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.