SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens
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ABSTRACT:
PROVIDER: PRJEB37671 | ENA |
REPOSITORIES: ENA
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Project description:Bats are the natural reservoir host for a number of zoonotic viruses, including Hendra virus (HeV) which causes severe clinical disease in humans and other susceptible hosts. Our understanding of the ability of bats to avoid clinical disease following infection with viruses such as HeV has come predominantly from in vitro studies focusing on innate immunity. Information on the early host response to infection in vivo is lacking and there is no comparative data on responses in bats compared with animals that succumb to disease. In this study, we examined the sites of HeV replication and the immune response of infected Australian black flying foxes and ferrets at 12, 36 and 60 hours post exposure (hpe). Viral antigen was detected at 60 hpe in bats and was confined to the lungs whereas in ferrets there was evidence of widespread viral RNA and antigen by 60 hpe. The mRNA expression of IFNs revealed antagonism of type I and III IFNs and a significant increase in the chemokine, CXCL10, in bat lung and spleen following infection. In ferrets, there was an increase in the transcription of IFN in the spleen following infection. Liquid chromatography tandem mass spectrometry (LC-MS/MS) on lung tissue from bats and ferrets was performed at 0 and 60 hpe to obtain a global overview of viral and host protein expression. Gene Ontology (GO) enrichment analysis of immune pathways revealed that six pathways, including a number involved in cell mediated immunity were more likely to be upregulated in bat lung compared to ferrets. GO analysis also revealed enrichment of the type I IFN signaling pathway in bats and ferrets. This study contributes important comparative data on differences in the dissemination of HeV and the first to provide comparative data on the activation of immune pathways in bats and ferrets in vivo following infection.
2020-03-03 | PXD017495 | Pride
Project description:BackgroundIn December, 2019, a novel zoonotic severe acute respiratory syndrome-related coronavirus emerged in China. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became pandemic within weeks and the number of human infections and severe cases is increasing. We aimed to investigate the susceptibilty of potential animal hosts and the risk of anthropozoonotic spill-over infections.MethodsWe intranasally inoculated nine fruit bats (Rousettus aegyptiacus), ferrets (Mustela putorius), pigs (Sus scrofa domesticus), and 17 chickens (Gallus gallus domesticus) with 105 TCID50 of a SARS-CoV-2 isolate per animal. Direct contact animals (n=3) were included 24 h after inoculation to test viral transmission. Animals were monitored for clinical signs and for virus shedding by nucleic acid extraction from nasal washes and rectal swabs (ferrets), oral swabs and pooled faeces samples (fruit bats), nasal and rectal swabs (pigs), or oropharyngeal and cloacal swabs (chickens) on days 2, 4, 8, 12, 16, and 21 after infection by quantitative RT-PCR (RT-qPCR). On days 4, 8, and 12, two inoculated animals (or three in the case of chickens) of each species were euthanised, and all remaining animals, including the contacts, were euthanised at day 21. All animals were subjected to autopsy and various tissues were collected for virus detection by RT-qPCR, histopathology immunohistochemistry, and in situ hybridisation. Presence of SARS-CoV-2 reactive antibodies was tested by indirect immunofluorescence assay and virus neutralisation test in samples collected before inoculation and at autopsy.FindingsPigs and chickens were not susceptible to SARS-CoV-2. All swabs, organ samples, and contact animals were negative for viral RNA, and none of the pigs or chickens seroconverted. Seven (78%) of nine fruit bats had a transient infection, with virus detectable by RT-qPCR, immunohistochemistry, and in situ hybridisation in the nasal cavity, associated with rhinitis. Viral RNA was also identified in the trachea, lung, and lung-associated lymphatic tissue in two animals euthanised at day 4. One of three contact bats became infected. More efficient virus replication but no clinical signs were observed in ferrets, with transmission to all three direct contact animals. Mild rhinitis was associated with viral antigen detection in the respiratory and olfactory epithelium. Prominent viral RNA loads of 0-104 viral genome copies per mL were detected in the upper respiratory tract of fruit bats and ferrets, and both species developed SARS-CoV-2-reactive antibodies reaching neutralising titres of up to 1/1024 after 21 days.InterpretationPigs and chickens could not be infected intranasally by SARS-CoV-2, whereas fruit bats showed characteristics of a reservoir host. Virus replication in ferrets resembled a subclinical human infection with efficient spread. Ferrets might serve as a useful model for further studies-eg, testing vaccines or antivirals.FundingGerman Federal Ministry of Food and Agriculture.
| S-EPMC7340389 | biostudies-literature
Project description:Jamaican fruit bats (Artibeus jamaicensis) naturally harbor a wide range of viruses of human relevance. These infections are typically mild in bats, suggesting unique features of their immune system. To better understand the immune response to viral infections in bats, we infected Jamaican fruit bats with the bat-derived influenza A virus H18N11. Using comparative single-cell RNA sequencing, we generated a single-cell atlas of the Jamaican fruit bat intestine and mesentery, the target organs of infection. Gene expression profiling showed that H18N11 infection resulted in a moderate induction of interferon-stimulated genes and transcriptional activation of immune cells. H18N11 infection was prominent in various leukocytes, including macrophages, B cells, and NK/T cells. Confirming these findings, human leukocytes, particularly macrophages, were also susceptible to H18N11, highlighting the zoonotic potential of this virus. Our study provides insight into the virus-host relationship and thus serves as a fundamental resource for further characterization of bat immunology.
2024-05-06 | GSE243982 | GEO
Project description:Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans. Bat species in both Chiropteran suborders host filoviruses, suggesting that bats may have coevolved with this viral family. Correlative data implicate bats as natural EBOV hosts, but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we modelled filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis. Bats were inoculated with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes. EBOV-infected bats supported systemic virus replication and shed infectious virus orally. In contrast, MARV replicated only transiently and was not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induced innate antiviral responses that EBOV efficiently suppressed. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrated an advantage for EBOV entry and replication early, respectively, in JFB cells. Overall, this study describes filovirus species-specific phenotypes for both JFB and their cells.
2025-03-02 | GSE288891 | GEO
Project description:The determinants of influenza transmission remain poorly understood. Swine influenza viruses preferentially attach to receptors found in the upper airways; however, most swine influenza viruses fail to transmit efficiently from swine to humans, and from human-to-human. The pandemic 2009 H1N1 (H1N1pdm) virus was a rare exception of a swine virus that acquired efficient transmissibility from human-to-human, and is reflected in efficient respiratory droplet transmission in ferrets. We hypothesize that virus-induced host responses in the upper airways correlate with airborne transmission in ferrets. To address this question, we used the H1N1pdm virus and swine influenza A/swine/Hong Kong/201/2010 (HK201) virus that has comparable titre in the ferret nasopharynx, but it exhibits differential transmissibility in ferrets via respiratory droplet route. We performed a transcriptomic analysis of tissues from the upper and lower respiratory tract from ferrets infected with either H1N1pdm or HK201 viruses using ferret-specific Agilent oligonucleotide arrays. We found differences in the kinetics of the innate immune response elicited by these two viruses that varied across tissues.
2017-03-31 | GSE79282 | GEO
Project description:While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) shows higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration and clinical symptoms compared to juvenile (≤6 months) and young adult (1-2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2.
2021-12-31 | GSE189619 | GEO
Project description:The ancestral sarbecovirus giving rise to SARS-CoV-2 is posited to have originated in bats. While SARS-CoV-2 causes asymptomatic to severe respiratory disease in humans, little is known about the biology, virus tropism, and immunity of SARS-CoV-2-like sarbecoviruses in bats. SARS-CoV-2 has been shown to infect multiple mammalian species, including various rodent species, non-human primates, and Egyptian fruit bats. Here, we investigate the Jamaican fruit bat (Artibeus jamaicensis) as a possible model species to study reservoir responses. SARS-CoV-2 can utilize Jamaican fruit bat ACE2 spike for entry in vitro. However, we find that SARS-CoV-2 Delta does not efficiently replicate in Jamaican fruit bats in vivo. We observe infectious virus in the lungs of only one animal on day 1 post inoculation and find no evidence for shedding or seroconversion. This is possibly due to host factors restricting virus egress after aborted replication. Furthermore, we observe no significant immune gene expression changes in the respiratory tract but do observe changes in the intestinal metabolome after inoculation. This suggests that, despite its broad host-range, SARS-CoV-2 is unable to infect all bat species and Jamaican fruit bats are not an appropriate model to study SARS-CoV-2 reservoir infection.
2025-01-15 | GSE254409 | GEO
Project description:Bats are remarkably long-lived for their size with many species living more than 20-40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigated requirements for malignant transformation in primary bat fibroblasts in four bat species - little brown bat (Myotis lucifugus), big brown bat (Eptesicus fuscus), cave nectar bat (Eonycteris spelaea) and Jamaican fruit bat (Artibeus jamaicensis) – spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence and express active telomerase. Bat cells displayed attenuated stress induced premature senescence with a dampened secretory phenotype. Unexpectedly, we discovered that bat cells could be readily transformed by only two oncogenic perturbations or “hits”: inactivation of either p53 or pRb and activation of oncogenic RASV12. This was surprising because other long-lived mammalian species require up to five hits for malignant transformation. Additionally, bat fibroblasts exhibited increased p53 and MDM2 transcript levels, and elevated p53-dependent apoptosis. The little brown bat showed a genomic duplication of the p53 gene. We hypothesize that bats evolved enhanced p53 activity through gene duplications and transcriptional upregulation as an additional anti-cancer strategy, similar to elephants. In summary, active telomerase and the small number of oncogenic hits sufficient to malignantly transform bat cells suggest that in vivo bats rely heavily on non-cell autonomous mechanisms of tumor suppression.
2025-02-21 | GSE262772 | GEO
Project description:As the only truly flying mammals, bats use their unique wing formed from elongated digits connected by membranes to power their flight. The forelimb of bats consists of four elongated digits (digits II-V) and one shorter digit (digit I) that is morphologically similar to the hindlimb digits. Elongation of bat forelimb digits is thought to results from changes in the temporal and spatial expression of a number of developmental genes. As a result, comparing gene expression profiles between short and elongated digit morphologies of the fore- and hindlimbs may elucidate the molecular mechanisms underlying digit elongation in bats. Here, we performed a large-scale analysis of gene expression of forelimb digit I, forelimb digits II-V, and all five hindlimb digits in Myotis ricketti using digital gene expression tag profiling approach. Results of this study not only implicate several developmental genes as robust candidates underlying digit elongation in bats, but also provide a better understanding of the genes involved in autopodial development in general. A large-scale analysis of gene expression of 3 different parts of autopods in Myotis ricketti using digital gene expression tag profiling approach.
2010-12-06 | E-GEOD-20038 | biostudies-arrayexpress
Project description:The goal of this study is to use newly designed ferret Agilent arrays to compare transcriptome profiles between wild type, CF3959(-/-) and CF3959(+/-) ferrets. Lung and trachea tissues from newborn and 15 day-old ferrets were RNA-extracted and subsequently analyzed by microarray. Using the newly designed ferret Agilent arrays, we compared the transcriptome profiles between wild type, CF3959(-/-) and CF3959(+/-) ferrets. Samples sets: RNA from a combination of trachea and lung tissue from 4 newborn wild type ferrets and 4 newborn CF3959(-/-) ferrets. In addition, lung tissue from two 15 day-old wild type, three 15 day-old CF3959(+/-) and three 15 day-old CF3959(-/-) ferrets was RNA-extracted and subsequently analyzed by microarray.
2014-07-18 | E-GEOD-49061 | biostudies-arrayexpress