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Abortive infection of bat fibroblasts with SARS-CoV-2

ABSTRACT: 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 SARS-CoV-2 infection of human and bat (Rhinolophus ferrumequinum) pluripotent cells and fibroblasts. Since bat cells do not express an ACE2 receptor that allows virus infection, we transduced the human ACE2 receptor into the cells and found that transduced cells can be infected with SARS-CoV-2. Compared to human ESCs-hA, infected bat iPSCs-hA produced about a 100-fold lower level of infectious virus and displayed lower toxicity. In contrast, bat fibroblasts (BEF-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.

ORGANISM(S): Rhinolophus ferrumequinum Homo sapiens

PROVIDER: GSE274964 | GEO | 2024/10/15

REPOSITORIES: GEO

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Project description:Bats are the most important natural reservoirs for a variety of emerging viruses that cause several illnesses in humans and other mammals. Increased viral shedding by bats is thought to be linked to an increased ability of many bat species to tolerate viral infection. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is thought to have originated in bats, since viruses with high sequence similarity have been detected in bat feces. However, there is no robust in vitro model for assessing the SARS-CoV-2 infection in the bat GI tract. Here, we established gastrointestinal organoid cultures from Jamaican fruit bats (JFB, Artibeus jamaicensis), which replicated the characteristic morphology of the gastrointestinal epithelium and showed tissue specific gene expression patterns and cell differentiation. To analyze whether JFB intestinal epithelial cells are susceptible to SARS-CoV-2, we performed in vitro infection experiments. Increased SARS-CoV-2 RNA was found in both cell lysates and supernatants from the infected organoids after 48 h, and sgRNA also was detected, indicating that the JFB intestinal epithelium supports limited viral replication. However, no infectious virus was released into the culture media, and no cytopathic effects were observed. Gene expression studies revealed a significant induction of type I interferon and inflammatory cytokine genes in response to active SARS-CoV-2 virus but not to TLR agonist treatment. Untargeted analysis of the organoid proteome using data-independent acquisition mass spectrometry (DIA-MS) revealed a significant increase in proteins and pathways associated with inflammatory signaling, cell turnover and repair, and SARS-CoV-2 infection. Collectively, our data suggest that primary intestinal epithelial cells from JFBs are largely resistant to SARS-CoV-2 infection and cell damage, likely because they are able to mount a strong antiviral interferon and regenerative response upon infection.

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Abortive infection of bat fibroblasts with SARS-CoV-2

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