tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2024 Oct 22;121(43):e2406773121.
doi: 10.1073/pnas.2406773121. Epub 2024 Oct 14. Abortive infection of bat fibroblasts with SARS-CoV-2
Punam Bisht[SUP] 1 [/SUP], Michael D Gallagher[SUP] 1 [/SUP], M Inmaculada Barrasa[SUP] 1 [/SUP], Julie Boucau[SUP] 2 [/SUP], Alfred Harding[SUP] 3 4 [/SUP], Marion Déjosez[SUP] 5 [/SUP], Carlos Godoy-Parejo[SUP] 5 [/SUP], Margaret E Bisher[SUP] 6 [/SUP], Giovanni de Nola[SUP] 6 [/SUP], Abigail K R Lytton-Jean[SUP] 6 [/SUP], Lee Gehrke[SUP] 3 4 [/SUP], Thomas P Zwaka[SUP] 5 [/SUP], Rudolf Jaenisch[SUP] 1 7 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; abortive infection; bat cells; innate immune system.
. 2024 Oct 22;121(43):e2406773121.
doi: 10.1073/pnas.2406773121. Epub 2024 Oct 14. Abortive infection of bat fibroblasts with SARS-CoV-2
Punam Bisht[SUP] 1 [/SUP], Michael D Gallagher[SUP] 1 [/SUP], M Inmaculada Barrasa[SUP] 1 [/SUP], Julie Boucau[SUP] 2 [/SUP], Alfred Harding[SUP] 3 4 [/SUP], Marion Déjosez[SUP] 5 [/SUP], Carlos Godoy-Parejo[SUP] 5 [/SUP], Margaret E Bisher[SUP] 6 [/SUP], Giovanni de Nola[SUP] 6 [/SUP], Abigail K R Lytton-Jean[SUP] 6 [/SUP], Lee Gehrke[SUP] 3 4 [/SUP], Thomas P Zwaka[SUP] 5 [/SUP], Rudolf Jaenisch[SUP] 1 7 [/SUP]
Affiliations
- PMID: 39401365
- DOI: 10.1073/pnas.2406773121
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.
Keywords: SARS-CoV-2; abortive infection; bat cells; innate immune system.