Project description:Bats harbour various viruses without severe symptoms and act as natural reservoirs. This tolerance of bats toward viral infections is assumed to be originated from the uniqueness of their immune system. However, how the innate immune response varies between primates and bats remains unclear. To illuminate differences in innate immune responses among animal species, we performed a comparative single-cell RNA-sequencing analysis on peripheral blood mononuclear cells (PBMCs) from four species including Egyptian fruit bats inoculated with various infectious stimuli.
2023-01-18 | GSE218199 | GEO
Project description:Viruses in bats captured in Russia
Project description:Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigated the antiviral RNA interference (RNAi) pathway in bat cells and discovered that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs (vsiRNAs) upon Sindbis virus (SINV) infection that were missing in human cells. Disruption of Dicer function resulted in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors (PRRs), such as retinoic acid-inducible gene I (RIG-I), with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.
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.
Project description:Bats are natural reservoirs for a large range of emerging viruses that cause lethal diseases in humans and domestic animals, but remain asymptomatic in bats. Understanding the host-pathogen interactions relies on the availability of relevant models including susceptible cells, derived from viral target tissues. To obtain bat cell types pertinent for the study of viral infection, we applied somatic reprogramming approach to Pteropus primary cells as initial substrates. Using the novel combination of three transcription factors: ESRRB, CDX2 and c-MYC, we generated reprogrammed cells exhibiting stem cells features.
Project description:Lobachevsky University DNAm dataset. Whole blood DNA Methylation (EPIC) profiles from healthy samples from two regions: central Russia (131 samples) and Yakutia (114 samples) obtained in the Laboratory of System Medicine for Healthy Aging, Lobachevsky State University of Nizhny Novgorod, Russia Dataset contains DNAm data from 245 healthy control samples from two regions: central Russia (131) and Yakutia (114). The following characteristics are available for all samples: sex, age, region. Healthy participants in the central Russia region were recruited in 2019–2022. Yakutian participants we recruited in 2022. All measurements were performed at the Laboratory of System Medicine for Healthy Aging, Lobachevsky State University of Nizhny Novgorod, Russia.
Project description:Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigated the antiviral RNA interference (RNAi) pathway in bat cells and discovered that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs (vsiRNAs) upon Sindbis virus (SINV) infection that were missing in human cells. Disruption of Dicer function resulted in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors (PRRs), such as retinoic acid-inducible gene I (RIG-I), with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.
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.
Project description:Bats are natural hosts for a wide diversity of viruses. While many of these viruses are highly pathogenic in humans, most do not appear to cause major symptoms in bats. These modern bat-specific characteristics are the result of past virus-host (co)evolution and virus-driven host adaptations. Innate immunity is the first line of defense against viruses in mammals, we aim at characterizing bat innate immunity in response to viruses. Using genome-wide and gene candidate evolutionary analyses, we found that many bat antiviral genes have undergone multiple duplication events in a lineage-specific manner, specifically in the Myotis bat lineage. We focus on Myotis yumanensis as a model in the Myotis lineage. We performed transcriptomic analyses and observed the upregulation of most mammalian genes implicated in the different steps of the innate immune response from sensing to interferon-stimulated genes (ISGs), showing the conservation of the core innate immunity. Our study will contribute to identifying adaptations that shaped bat innate immunity. These adaptations may contribute to the bat-virus specificity and influence viral emergence to another mammalian host