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Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection.

ABSTRACT: Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, Artibeus jamaicensis) intestinal organoid model of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Upon infection with SARS-CoV-2, increased viral RNA and subgenomic RNA was detected, but no infectious virus was released, indicating that JFB organoids support only limited viral replication but not viral reproduction. SARS-CoV-2 replication was associated with significantly increased gene expression of type I interferons and inflammatory cytokines. Interestingly, SARS-CoV-2 also caused enhanced formation and growth of JFB organoids. Proteomics revealed an increase in inflammatory signaling, cell turnover, cell repair, and SARS-CoV-2 infection pathways. Collectively, our findings suggest that primary JFB intestinal epithelial cells mount successful antiviral interferon responses and that SARS-CoV-2 infection in JFB cells induces protective regenerative pathways.

SUBMITTER: Hashimi M

PROVIDER: S-EPMC10613288 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection.

Hashimi Marziah M Sebrell T Andrew TA Hedges Jodi F JF Snyder Deann D Lyon Katrina N KN Byrum Stephanie D SD Mackintosh Samuel G SG Crowley Dan D Cherne Michelle D MD Skwarchuk David D Robison Amanda A Sidar Barkan B Kunze Anja A Loveday Emma K EK Taylor Matthew P MP Chang Connie B CB Wilking James N JN Walk Seth T ST Schountz Tony T Jutila Mark A MA Bimczok Diane D

Nature communications 20231028 1

Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, Artibeus jamaicensis) intestinal organoid model of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Upon infection with SARS-CoV-2, increased viral RNA and subgenomic RNA was detected, but no infectious virus was released, indica ...[more]

PMID: 37898615

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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.

Dataset Information

Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection.

Publications

Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection.

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