Effects of Overexpression of the Egyptian Fruit Bat Innate Immune Genes on Filovirus Infections in the Host Cells (original) (raw)
Related papers
PLOS One, 2011
Bats harbor several highly pathogenic zoonotic viruses including Rabies, Marburg, and henipaviruses, without overt clinical symptoms in the animals. It has been suspected that bats might have evolved particularly effective mechanisms to suppress viral replication. Here, we investigated interferon (IFN) response, -induction, -secretion and -signaling in epithelial-like cells of the relevant and abundant African fruit bat species, Eidolon helvum (E. helvum). Immortalized cell lines were generated; their potential to induce and react on IFN was confirmed, and biological assays were adapted to application in bat cell cultures, enabling comparison of landmark IFN properties with that of common mammalian cell lines. E. helvum cells were fully capable of reacting to viral and artificial IFN stimuli. E. helvum cells showed highest IFN mRNA induction, highly productive IFN protein secretion, and evidence of efficient IFN stimulated gene induction. In an Alphavirus infection model, O'nyong-nyong virus exhibited strong IFN induction but evaded the IFN response by translational rather than transcriptional shutoff, similar to other Alphavirus infections. These novel IFN-competent cell lines will allow comparative research on zoonotic, bat-borne viruses in order to model mechanisms of viral maintenance and emergence in bat reservoirs.
Cloning, expression and antiviral activity of IFNγ from the Australian fruit bat, Pteropus alecto
Developmental & Comparative Immunology, 2012
Bats are natural reservoir hosts to a variety of viruses, many of which cause morbidity and mortality in other mammals. Currently there is a paucity of information regarding the nature of the immune response to viral infections in bats, partly due to a lack of appropriate bat specific reagents. IFNc plays a key role in controlling viral replication and coordinating a response for long term control of viral infection. Here we describe the cloning and expression of IFNc from the Australian flying fox, Pteropus alecto and the generation of mouse monoclonal and chicken egg yolk antibodies specific to bat IFNc. Our results demonstrate that P. alecto IFNc is conserved with IFNc from other species and is induced in bat splenocytes following stimulation with T cell mitogens. P. alecto IFNc has antiviral activity on Semliki forest virus in cell lines from P. alecto and the microbat, Tadarida brasiliensis. Additionally recombinant bat IFNc was able to mitigate Hendra virus infection in P. alecto cells. These results provide the first evidence for an antiviral role for bat IFNc in vitro in addition to the application of important immunological reagents for further studies of bat antiviral immunity.
Marburg and Ebola virus infections elicit a complex, muted inflammatory state in bats
2020
The Marburg and Ebola filoviruses cause a severe, often fatal, disease in humans and nonhuman primates but have only subclinical effects in bats, including Egyptian rousettes, which are a natural reservoir of Marburg virus. A fundamental question is why these viruses are highly pathogenic in humans but fail to cause disease in bats. To understand how bats resist the disease caused by filoviruses, we infected one cohort of Egyptian rousette bats with Marburg virus and another cohort with Ebola virus and harvested multiple tissues for mRNA expression analysis. While virus transcripts were found primarily in the liver, Principal component analysis (PCA) revealed coordinated changes across multiple tissues. Gene signatures in kidney and liver pointed at induction of vasodilation, reduction of coagulation and changes in the regulation of iron metabolism. Signatures of immune response detected in spleen and liver indicated a robust anti-inflammatory state signified by macrophages in the M...
The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity
Cell, 2018
Bats harbor many viruses asymptomatically, including several notorious for causing extreme virulence in humans. To identify differences between antiviral mechanisms in humans and bats, we sequenced, assembled, and analyzed the genome of Rousettus aegyptiacus, a natural reservoir of Marburg virus and the only known reservoir for any filovirus. We found an expanded and diversified KLRC/KLRD family of natural killer cell receptors, MHC class I genes, and type I interferons, which dramatically differ from their functional counterparts in other mammals. Such concerted evolution of key components of bat immunity is strongly suggestive of novel modes of antiviral defense. An evaluation of the theoretical function of these genes suggests that an inhibitory immune state may exist in bats. Based on our findings, we hypothesize that tolerance of viral infection, rather than enhanced potency of antiviral defenses, may be a key mechanism by which bats asymptomatically host viruses that are patho...
Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells
Scientific Reports, 2016
The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of se...
Novel Insights Into Immune Systems of Bats
Frontiers in Immunology
In recent years, viruses similar to those that cause serious disease in humans and other mammals have been detected in apparently healthy bats. These include filoviruses, paramyxoviruses, and coronaviruses that cause severe diseases such as Ebola virus disease, Marburg haemorrhagic fever and severe acute respiratory syndrome (SARS) in humans. The evolution of flight in bats seem to have selected for a unique set of antiviral immune responses that control virus propagation, while limiting self-damaging inflammatory responses. Here, we summarize our current understanding of antiviral immune responses in bats and discuss their ability to co-exist with emerging viruses that cause serious disease in other mammals. We highlight how this knowledge may help us to predict viral spillovers into new hosts and discuss future directions for the field.
Bats As A Viral Reservoir: A Short Review Of Their Ecological Characters And Immune System
Proceedings of the 1st International Conference in One Health (ICOH 2017), 2018
Bats are reported as natural reservoir host of several viruses, many of which cause severe human disease. Infected bats usually do not show any clinical symptoms and persistently infected. Bats immunity against viruses is an evolutional process of self-defense created by ecological adaptation between host and pathogen. Bats have unique characters which support them as a viral reservoir, whereas RNA viruses which are commonly carried by bats take an advantage of these characteristics to survive. The role of bats as reservoirs is also supported by several differences of immune system than other mammals. Several studies on molecular factors of bats immune system lead to a hypothesis that bats are able to control viral replication very early in the immune response through innate antiviral mechanism. However, to complete understanding of the nature of immune responses of bats to the virus still needs a lot of study. Advance technology on molecular techniques revealed the immune factors and provided numerous data about molecular factors in bat immunity, however comprehensive studies about morphology of bats immune organs are still lacking. One of the important immune organs which have functional variations due to their structural differences between species is the spleen, which will be our main focus of study in the future. We hope that the result of our study will be able to provide the database on the morphology and physiology of bat spleen and give better understanding on bats immune system.
PloS one, 2011
Bats are natural reservoirs for a spectrum of infectious zoonotic diseases including the recently emerged henipaviruses (Hendra and Nipah viruses). Henipaviruses have been observed both naturally and experimentally to cause serious and often fatal disease in many different mammal species, including humans. Interestingly, infection of the flying fox with henipaviruses occurs in the absence of clinical disease. The extreme variation in the disease pattern between humans and bats has led to an investigation into the effects of henipavirus infection on the innate immune response in bat cell lines. We report that henipavirus infection does not result in the induction of interferon expression, and the viruses also inhibit interferon signaling. We also confirm that the interferon production and signaling block in bat cells is not due to differing viral protein expression levels between human and bat hosts. This information, in addition to the known lack of clinical signs in bats following ...