The Experts below are selected from a list of 588 Experts worldwide ranked by ideXlab platform

Linfa Wang - One of the best experts on this subject based on the ideXlab platform.

  • Complementary regulation of caspase-1 and IL-1β reveals additional mechanisms of dampened inflammation in bats.
    Proceedings of the National Academy of Sciences of the United States of America, 2020
    Co-Authors: Geraldine Goh, Matae Ahn, Aaron T. Irving, Feng Zhu, Lim Beng Lee, Dahai Luo, Linfa Wang
    Abstract:

    Bats have emerged as unique mammalian vectors harboring a diverse range of highly lethal zoonotic viruses with minimal clinical disease. Despite having sustained complete genomic loss of AIM2, regulation of the downstream inflammasome response in bats is unknown. AIM2 sensing of cytoplasmic DNA triggers ASC aggregation and recruits caspase-1, the central inflammasome effector enzyme, triggering cleavage of cytokines such as IL-1β and inducing GSDMD-mediated pyroptotic cell death. Restoration of AIM2 in bat cells led to intact ASC speck formation, but intriguingly resulted in a lack of caspase-1 or consequent IL-1β activation. We further identified two residues undergoing positive selection pressures in Pteropus alecto caspase-1 that abrogate its enzymatic function and are crucial in human caspase-1 activity. Functional analysis of another bat lineage revealed a targeted mechanism for loss of Myotis davidii IL-1β cleavage and elucidated an inverse complementary relationship between caspase-1 and IL-1β, resulting in overall diminished signaling across bats of both suborders. Thus we report strategies that additionally undermine downstream inflammasome signaling in bats, limiting an overactive immune response against pathogens while potentially producing an antiinflammatory state resistant to diseases such as atherosclerosis, aging, and neurodegeneration.

  • Optimizing dissection, sample collection and cell isolation protocols for frugivorous bats
    Methods in Ecology and Evolution, 2019
    Co-Authors: Aaron T. Irving, Hume Field, Joanne Meers, Gary Crameri, Florent Ginhoux, Charles-antoine Dutertre, Victoria Boyd, Milou H. Dekkers, Linfa Wang
    Abstract:

    Bats are becoming increasingly important as an experimental model due to their unique biological features. These include the ability of powered flight, minimal consequences from a heightened metabolic state, extended longevity in most species and minimal inflammation in response to most otherwise pathogenic viruses. To date there has been limited work done on the optimal procedures for necropsy, extraction of tissues or preparation of cell suspensions for downstream experimental work. Here we use Pteropus alecto black flying fox as an example model of the fruit bat to develop optimal procedures for anaesthetizing, necropsy methods, safety, sequence and protocols for cell/tissue extraction and isolation protocols. These methods were successfully used to yield high-quality RNA, DNA and protein samples from tissues along with viable cells for various molecular and immunological studies. Procedures utilized are suitable for comparative biology studies with most protocols being directly modified from those used in mice and humans. While mainly optimized for the larger fruit bats (flying foxes) in this study, the majority of protocols can readily be adapted to all species of bats. This study provides the framework for greater consistency with in vivo bat experiments, application for comparative biology studies and greater engagement of the bat community for suitable protocols to be harmoniously adopted.

  • The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression Kinetics with Atypical RNASEL Induction.
    Journal of immunology (Baltimore Md. : 1950), 2017
    Co-Authors: Pamela C. De La Cruz-rivera, Linfa Wang, Mohammed Kanchwala, Hanquan Liang, Ashwani Kumar, Chao Xing, John W. Schoggins
    Abstract:

    Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity are unknown, but they may be linked to unique immunological features that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to viral infection by inducing IFNs, which trigger antiviral defenses through IFN-stimulated gene (ISG) expression. Although the IFN system of several bats is characterized at the genomic level, less is known about bat IFN-mediated transcriptional responses. In this article, we show that IFN signaling in bat cells from the black flying fox (Pteropus alecto) consists of conserved and unique ISG expression profiles. In IFN-stimulated cells, bat ISGs comprise two unique temporal subclusters with similar early induction kinetics but distinct late-phase declines. In contrast, human ISGs lack this decline phase and remained elevated for longer periods. Notably, in unstimulated cells, bat ISGs were expressed more highly than their human counterparts. We also found that the antiviral effector 2-5A-dependent endoribonuclease, which is not an ISG in humans, is highly IFN inducible in black flying fox cells and contributes to cell-intrinsic control of viral infection. These studies reveal distinctive innate immune features that may underlie a unique virus-host relationship in bats.

  • Insights into the ancestral organisation of the mammalian MHC class II region from the genome of the pteropid bat, Pteropus alecto.
    BMC genomics, 2017
    Co-Authors: Mary Tachedjian, Linfa Wang, Michelle L. Baker
    Abstract:

    Bats are an extremely successful group of mammals and possess a variety of unique characteristics, including their ability to co-exist with a diverse range of pathogens. The major histocompatibility complex (MHC) is the most gene dense and polymorphic region of the genome and MHC class II (MHC-II) molecules play a vital role in the presentation of antigens derived from extracellular pathogens and activation of the adaptive immune response. Characterisation of the MHC-II region of bats is crucial for understanding the evolution of the MHC and of the role of pathogens in shaping the immune system. Here we describe the relatively contracted MHC-II region of the Australian black flying-fox (Pteropus alecto), providing the first detailed insight into the MHC-II region of any species of bat. Twelve MHC-II genes, including one locus (DRB2) located outside the class II region, were identified on a single scaffold in the bat genome. The presence of a class II locus outside the MHC-II region is atypical and provides evidence for an ancient class II duplication block. Two non-classical loci, DO and DM and two classical, DQ and DR loci, were identified in P. alecto. A putative classical, DPB pseudogene was also identified. The bat’s antigen processing cluster, though contracted, remains highly conserved, thus supporting its importance in antigen presentation and disease resistance. This detailed characterisation of the bat MHC-II region helps to fill a phylogenetic gap in the evolution of the mammalian class II region and is a stepping stone towards better understanding of the immune responses in bats to viral, bacterial, fungal and parasitic infections.

  • Insights into the ancestral organisation of the mammalian MHC class II region from the genome of the pteropid bat, Pteropus alecto
    BMC, 2017
    Co-Authors: Mary Tachedjian, Linfa Wang, Michelle L. Baker
    Abstract:

    Abstract Background Bats are an extremely successful group of mammals and possess a variety of unique characteristics, including their ability to co-exist with a diverse range of pathogens. The major histocompatibility complex (MHC) is the most gene dense and polymorphic region of the genome and MHC class II (MHC-II) molecules play a vital role in the presentation of antigens derived from extracellular pathogens and activation of the adaptive immune response. Characterisation of the MHC-II region of bats is crucial for understanding the evolution of the MHC and of the role of pathogens in shaping the immune system. Results Here we describe the relatively contracted MHC-II region of the Australian black flying-fox (Pteropus alecto), providing the first detailed insight into the MHC-II region of any species of bat. Twelve MHC-II genes, including one locus (DRB2) located outside the class II region, were identified on a single scaffold in the bat genome. The presence of a class II locus outside the MHC-II region is atypical and provides evidence for an ancient class II duplication block. Two non-classical loci, DO and DM and two classical, DQ and DR loci, were identified in P. alecto. A putative classical, DPB pseudogene was also identified. The bat’s antigen processing cluster, though contracted, remains highly conserved, thus supporting its importance in antigen presentation and disease resistance. Conclusions This detailed characterisation of the bat MHC-II region helps to fill a phylogenetic gap in the evolution of the mammalian class II region and is a stepping stone towards better understanding of the immune responses in bats to viral, bacterial, fungal and parasitic infections

Michelle L. Baker - One of the best experts on this subject based on the ideXlab platform.

  • studies on b cells in the fruit eating black flying fox Pteropus alecto
    Frontiers in Immunology, 2019
    Co-Authors: Pravin Periasamy, Aaron T. Irving, Charles-antoine Dutertre, Paul E. Hutchinson, Jinmiao Chen, Isabelle Bonne, Shahana Shereene Shahul Hameed, Pavithra Selvam, Katja Fink, Michelle L. Baker
    Abstract:

    The ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat’s immunity. Here, we report a panel of cross-reactive antibodies against MHC-II, NK1.1, CD3, CD21, CD27, and immunoglobulin (Ig), that allows flow cytometry analysis of B, T and NK cell populations in two different fruit-eating bat species namely, P. alecto and E. spelaea. Results confirmed predominance of T cells in the spleen and blood of bats, as previously reported by us. However, the percentages of B cells in bone marrow and NK cells in spleen varied greatly between wild caught P. alecto bats and E. spelaea colony bats, which may reflect inherent differences of their immune system or different immune status. Other features of bat B cells were investigated. A significant increase in sIg+ B cell population was observed in the spleen and blood from LPS-injected bats but not from poly I:C-injected bats, supporting T-independent polyclonal B cell activation by LPS. Furthermore, using an in vitro calcium release assay, P. alecto B cells exhibited significant calcium release upon cross-linking of their B cell receptor. Together, this work contributes to improve our knowledge of bat adaptive immunity in particular B cells.

  • Insights into the ancestral organisation of the mammalian MHC class II region from the genome of the pteropid bat, Pteropus alecto.
    BMC genomics, 2017
    Co-Authors: Mary Tachedjian, Linfa Wang, Michelle L. Baker
    Abstract:

    Bats are an extremely successful group of mammals and possess a variety of unique characteristics, including their ability to co-exist with a diverse range of pathogens. The major histocompatibility complex (MHC) is the most gene dense and polymorphic region of the genome and MHC class II (MHC-II) molecules play a vital role in the presentation of antigens derived from extracellular pathogens and activation of the adaptive immune response. Characterisation of the MHC-II region of bats is crucial for understanding the evolution of the MHC and of the role of pathogens in shaping the immune system. Here we describe the relatively contracted MHC-II region of the Australian black flying-fox (Pteropus alecto), providing the first detailed insight into the MHC-II region of any species of bat. Twelve MHC-II genes, including one locus (DRB2) located outside the class II region, were identified on a single scaffold in the bat genome. The presence of a class II locus outside the MHC-II region is atypical and provides evidence for an ancient class II duplication block. Two non-classical loci, DO and DM and two classical, DQ and DR loci, were identified in P. alecto. A putative classical, DPB pseudogene was also identified. The bat’s antigen processing cluster, though contracted, remains highly conserved, thus supporting its importance in antigen presentation and disease resistance. This detailed characterisation of the bat MHC-II region helps to fill a phylogenetic gap in the evolution of the mammalian class II region and is a stepping stone towards better understanding of the immune responses in bats to viral, bacterial, fungal and parasitic infections.

  • Insights into the ancestral organisation of the mammalian MHC class II region from the genome of the pteropid bat, Pteropus alecto
    BMC, 2017
    Co-Authors: Mary Tachedjian, Linfa Wang, Michelle L. Baker
    Abstract:

    Abstract Background Bats are an extremely successful group of mammals and possess a variety of unique characteristics, including their ability to co-exist with a diverse range of pathogens. The major histocompatibility complex (MHC) is the most gene dense and polymorphic region of the genome and MHC class II (MHC-II) molecules play a vital role in the presentation of antigens derived from extracellular pathogens and activation of the adaptive immune response. Characterisation of the MHC-II region of bats is crucial for understanding the evolution of the MHC and of the role of pathogens in shaping the immune system. Results Here we describe the relatively contracted MHC-II region of the Australian black flying-fox (Pteropus alecto), providing the first detailed insight into the MHC-II region of any species of bat. Twelve MHC-II genes, including one locus (DRB2) located outside the class II region, were identified on a single scaffold in the bat genome. The presence of a class II locus outside the MHC-II region is atypical and provides evidence for an ancient class II duplication block. Two non-classical loci, DO and DM and two classical, DQ and DR loci, were identified in P. alecto. A putative classical, DPB pseudogene was also identified. The bat’s antigen processing cluster, though contracted, remains highly conserved, thus supporting its importance in antigen presentation and disease resistance. Conclusions This detailed characterisation of the bat MHC-II region helps to fill a phylogenetic gap in the evolution of the mammalian class II region and is a stepping stone towards better understanding of the immune responses in bats to viral, bacterial, fungal and parasitic infections

  • Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto
    Scientific reports, 2016
    Co-Authors: Julia María Martínez Gómez, Michelle L. Baker, Linfa Wang, Gary Crameri, Florent Ginhoux, Aaron T. Irving, Charles-antoine Dutertre, Pravin Periasamy, Sylvie Alonso
    Abstract:

    The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat’s immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8+ T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4+ subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat’s immunity, opening up new perspectives of therapeutic interventions for humans.

  • Purification and characterisation of immunoglobulins from the Australian black flying fox (Pteropus alecto) using anti-fab affinity chromatography reveals the low abundance of IgA
    2016
    Co-Authors: James W. Wynne, Michelle L. Baker, Christopher Cowled, Brian J. Shiell, Antonio Di Rubbo, Gary Beddome, Grantley R. Peck, Jing Huang, Samantha L. Grimley, Wojtek P. Michalski
    Abstract:

    There is now an overwhelming body of evidence that implicates bats in the dissemination of a long list of emerging and re-emerging viral agents, often causing illnesses or death in both animals and humans. Despite this, there is a paucity of information regarding the immunological mechanisms by which bats coexist with highly pathogenic viruses. Immunoglobulins are major components of the adaptive immune system. Early studies found bats may have quantitatively lower antibody responses to model antigens compared to conventional laboratory animals. To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. We employed a novel strategy, where IgG was initially purified and used to generate anti-Fab specific antibodies. Immobilised anti-Fab specific antibodies were then used to capture other immunoglobulins from IgG depleted serum. While high quantities of IgM were successfully isolated from serum, IgA was not. Only trace quantities of IgA were detected in the serum by mass spectrometry. Immobilised ligands specific to IgA (Jacalin, Peptide M and staphylococcal superantigen-like protein) also failed to capture P. alecto IgA from serum. IgM was the second most abundant serum antibody after IgG. A survey of mucosal secretions found IgG was the dominant antibody class rather than IgA. Our study demonstrates healthy P. alecto bats have markedly less serum IgA than expected. Higher quantities of IgG in mucosal secretions may be compensation for this low abundance or lack of IgA. Knowledge and reagents developed withi

Hume Field - One of the best experts on this subject based on the ideXlab platform.

  • Optimizing dissection, sample collection and cell isolation protocols for frugivorous bats
    Methods in Ecology and Evolution, 2019
    Co-Authors: Aaron T. Irving, Hume Field, Joanne Meers, Gary Crameri, Florent Ginhoux, Charles-antoine Dutertre, Victoria Boyd, Milou H. Dekkers, Linfa Wang
    Abstract:

    Bats are becoming increasingly important as an experimental model due to their unique biological features. These include the ability of powered flight, minimal consequences from a heightened metabolic state, extended longevity in most species and minimal inflammation in response to most otherwise pathogenic viruses. To date there has been limited work done on the optimal procedures for necropsy, extraction of tissues or preparation of cell suspensions for downstream experimental work. Here we use Pteropus alecto black flying fox as an example model of the fruit bat to develop optimal procedures for anaesthetizing, necropsy methods, safety, sequence and protocols for cell/tissue extraction and isolation protocols. These methods were successfully used to yield high-quality RNA, DNA and protein samples from tissues along with viable cells for various molecular and immunological studies. Procedures utilized are suitable for comparative biology studies with most protocols being directly modified from those used in mice and humans. While mainly optimized for the larger fruit bats (flying foxes) in this study, the majority of protocols can readily be adapted to all species of bats. This study provides the framework for greater consistency with in vivo bat experiments, application for comparative biology studies and greater engagement of the bat community for suitable protocols to be harmoniously adopted.

  • Hematology and Plasma Biochemistry of Wild Spectacled Flying Foxes ( Pteropus conspicillatus) in Australia.
    Journal of Wildlife Diseases, 2018
    Co-Authors: Lee Mcmichael, Joanne Meers, Daniel Edson, David G. Mayer, Steven R. Kopp, Adam Mckeown, Cecilia A. Sánchez, Hume Field
    Abstract:

    The spectacled flying fox (Pteropus conspicillatus) is listed as vulnerable to extinction in Australia. The species' restricted population is in decline, putatively attributed to decreasing habitat, climatic extremes, anthropogenic activities, and more recently, mass mortality events associated with tick paralysis and neonatal cleft palate syndrome. Knowledge of fundamental physiologic parameters of the species is limited. To address this knowledge gap, we sampled 50 wild-caught adult spectacled flying foxes in June (winter) in Far North Queensland, Australia. Hematologic and plasma biochemistry reference ranges were established, and a suite of urine biochemistry analytes were measured. Analyte values were compared within spectacled flying fox sex cohorts and between the spectacled flying fox and the paraphyletic black flying fox (Pteropus alecto). Significant differences in multiple analytes (including erythrocyte, leucocyte, plasma, and urine biochemistry) were found between spectacled flying fox sex cohorts. The majority of spectacled flying fox analyte values did not differ significantly from black flying fox values. Of those analytes that differed between species (erythrocyte, platelet, eosinophil, liver enzyme, and triglyceride levels), the majority were plausibly explained by intraerythrocyte parasite burden and food resource type. Our findings provide baseline data essential to measure and meaningfully interpret flying fox population health in ecologic, conservation, and epidemiologic contexts.

  • No Evidence of Hendra Virus Infection in the Australian Flying‐fox Ectoparasite Genus Cyclopodia
    Zoonoses and public health, 2016
    Co-Authors: Miranda E Vidgen, Hume Field, Daniel Edson, A. F. Van Den Hurk, Craig S Smith
    Abstract:

    Hendra virus (HeV) causes potentially fatal respiratory and/or neurological disease in both horses and humans. Although Australian flying-foxes of the genus Pteropus have been identified as reservoir hosts, the precise mechanism of HeV transmission has yet to be elucidated. To date, there has been limited investigation into the role of haematophagous insects as vectors of HeV. This mode of transmission is particularly relevant because Australian flying-foxes host the bat-specific blood-feeding ectoparasites of the genus Cyclopodia (Diptera: Nycteribiidae), also known as bat flies. Using molecular detection methods, we screened for HeV RNA in 183 bat flies collected from flying-foxes inhabiting a roost in Boonah, Queensland, Australia. It was subsequently demonstrated that during the study period, Pteropus alecto in this roost had a HeV RNA prevalence between 2 and 15% (95% CI [1, 6] to [8, 26], respectively). We found no evidence of HeV in any bat flies tested, including 10 bat flies collected from P. alecto in which we detected HeV RNA. Our negative findings are consistent with previous findings and provide additional evidence that bat flies do not play a primary role in HeV transmission.

  • PHYSIOLOGIC BIOMARKERS AND HENDRA VIRUS INFECTION IN AUSTRALIAN BLACK FLYING FOXES (Pteropus alecto).
    Journal of Wildlife Diseases, 2016
    Co-Authors: Lee Mcmichael, Joanne Meers, Daniel Edson, David G. Mayer, Alice Broos, Steven R. Kopp, Hume Field
    Abstract:

    Abstract Bats of the genus Pteropus (Pteropodidae), colloquially known as flying foxes, are recognized as the natural reservoir of Hendra virus, a zoonotic paramyxovirus responsible for mortality in horses and humans. Some previous studies have suggested that physiologic and ecologic factors promote Hendra virus infection in flying foxes, and by extension, spillover to horses and humans. However, the impact of Hendra virus infection on relevant physiologic biomarkers in flying foxes has not been measured. Over 12 mo in eastern Australia, we captured and sampled 446 individual black flying foxes (Pteropus alecto), a putative primary reservoir host species, and measured a suite of hematologic, plasma biochemistry, and urinary biomarkers. All mean hematologic and biochemical values in both Hendra virus–positive and virus–negative cohorts were within the published reference ranges for black flying foxes. We found no association between Hendra virus infection (as indicated by PCR detection of Hendra virus RNA)...

  • RESEARCH ARTICLE Haematology and Plasma Biochemistry of
    2016
    Co-Authors: Wild Black Flying-foxes, Lee Mcmichael, Joanne Meers, Daniel Edson, Amanda Mclaughlin, David Mayer, Hume Field
    Abstract:

    This paper establishes reference ranges for hematologic and plasma biochemistry values in wild Black flying-foxes (Pteropus alecto) captured in South East Queensland, Australia. Val-ues were found to be consistent with those of other Pteropus species. Four hundred and forty-seven animals were sampled over 12 months and significant differences were found be-tween age, sex, reproductive and body condition cohorts in the sample population. Mean val-ues for each cohort fell within the determined normal adult reference range, with the exception of elevated levels of alkaline phosphatase in juvenile animals. Hematologic and biochemistry parameters of injured animals showed little or no deviation from the normal ref-erence values for minor injuries, while two animals with more severe injury or abscessation showed leucocytosis, anaemia, thrombocytosis, hyperglobulinemia and hypoalbuminemia

Christopher Cowled - One of the best experts on this subject based on the ideXlab platform.

  • Purification and characterisation of immunoglobulins from the Australian black flying fox (Pteropus alecto) using anti-fab affinity chromatography reveals the low abundance of IgA
    2016
    Co-Authors: James W. Wynne, Michelle L. Baker, Christopher Cowled, Brian J. Shiell, Antonio Di Rubbo, Gary Beddome, Grantley R. Peck, Jing Huang, Samantha L. Grimley, Wojtek P. Michalski
    Abstract:

    There is now an overwhelming body of evidence that implicates bats in the dissemination of a long list of emerging and re-emerging viral agents, often causing illnesses or death in both animals and humans. Despite this, there is a paucity of information regarding the immunological mechanisms by which bats coexist with highly pathogenic viruses. Immunoglobulins are major components of the adaptive immune system. Early studies found bats may have quantitatively lower antibody responses to model antigens compared to conventional laboratory animals. To further understand the antibody response of bats, the present study purified and characterised the major immunoglobulin classes from healthy black flying foxes, Pteropus alecto. We employed a novel strategy, where IgG was initially purified and used to generate anti-Fab specific antibodies. Immobilised anti-Fab specific antibodies were then used to capture other immunoglobulins from IgG depleted serum. While high quantities of IgM were successfully isolated from serum, IgA was not. Only trace quantities of IgA were detected in the serum by mass spectrometry. Immobilised ligands specific to IgA (Jacalin, Peptide M and staphylococcal superantigen-like protein) also failed to capture P. alecto IgA from serum. IgM was the second most abundant serum antibody after IgG. A survey of mucosal secretions found IgG was the dominant antibody class rather than IgA. Our study demonstrates healthy P. alecto bats have markedly less serum IgA than expected. Higher quantities of IgG in mucosal secretions may be compensation for this low abundance or lack of IgA. Knowledge and reagents developed withi

  • Contraction of the type I IFN locus and unusual constitutive expression of IFN-α in bats.
    Proceedings of the National Academy of Sciences of the United States of America, 2016
    Co-Authors: Peng Zhou, Ina Smith, Christopher Cowled, Mary Tachedjian, Lawrence Mok, James W. Wynne, Victoria Boyd, Jie Cui, Wojtek P. Michalski
    Abstract:

    Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-α loci. Furthermore, the three IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-α results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses.

  • characterisation of novel micrornas in the black flying fox Pteropus alecto by deep sequencing
    BMC Genomics, 2014
    Co-Authors: Christopher Cowled, Kristie A Jenkins, Mark Tizard, Pauline Cottee, Vladimir A Likic, Cameron R. Stewart, Mary Tachedjian, Glenn A. Marsh, Marc R Friedlander, Peng Zhou
    Abstract:

    Background: Bats are a major source of new and emerging viral diseases. Despite the fact that bats carry and shed highly pathogenic viruses including Ebola, Nipah and SARS, they rarely display clinical symptoms of infection. Host factors influencing viral replication are poorly understood in bats and are likely to include both pre- and post-transcriptional regulatory mechanisms. MicroRNAs are a major mechanism of post-transcriptional gene regulation, however very little is known about them in bats. Results: This study describes 399 microRNAs identified by deep sequencing of small RNA isolated from tissues of the Black flying fox, Pteropus alecto, a confirmed natural reservoir of the human pathogens Hendra virus and Australian bat lyssavirus. Of the microRNAs identified, more than 100 are unique amongst vertebrates, including a subset containing mutations in critical seed regions. Clusters of rapidly-evolving microRNAs were identified, as well as microRNAs predicted to target genes involved in antiviral immunity, the DNA damage response, apoptosis and autophagy. Closer inspection of the predicted targets for several highly supported novel miRNA candidates suggests putative roles in host-virus interaction. Conclusions: MicroRNAs are likely to play major roles in regulating virus-host interaction in bats, via dampening of inflammatory responses (limiting the effects of immunopathology), and directly limiting the extent of viral replication, either through restricting the availability of essential factors or by controlling apoptosis. Characterisation of the bat microRNA repertoire is an essential step towards understanding transcriptional regulation during viral infection, and will assist in the identification of mechanisms that enable bats to act as natural virus reservoirs. This in turn will facilitate the development of antiviral strategies for use in humans and other species.

  • irf7 in the australian black flying fox Pteropus alecto evidence for a unique expression pattern and functional conservation
    PLOS ONE, 2014
    Co-Authors: Peng Cheng Zhou, Christopher Cowled, Linfa Wang, Ashley Mansell, Paul Monaghan, Diane Green, Lijun Wu, Michelle L. Baker
    Abstract:

    As the only flying mammal, bats harbor a number of emerging and re-emerging viruses, many of which cause severe diseases in humans and other mammals yet result in no clinical symptoms in bats. As the master regulator of the interferon (IFN)-dependent immune response, IFN regulatory factor 7 (IRF7) plays a central role in innate antiviral immunity. To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Our results demonstrate that bat IRF7 retains the ability to bind to MyD88 and activate the IFN response despite unique changes in the MyD88 binding domain. We also demonstrate that bat IRF7 has a unique expression pattern across both immune and non-immune related tissues and is inducible by double-strand RNA. The broad tissue distribution of IRF7 may provide bats with an enhanced ability to rapidly activate the IFN response in a wider range of tissues compared to other mammals. The importance of IRF7 in antiviral activity against the bat reovirus, Pulau virus was confirmed by siRNA knockdown of IRF7 in bat cells resulting in enhanced viral replication. Our results highlight the importance of IRF7 in innate antiviral immunity in bats.

  • IRF7 in the Australian Black Flying Fox, Pteropus alecto - Table 1 : Evidence for a Unique Expression Pattern and Functional Conservation
    2014
    Co-Authors: Peng Zhou, Christopher Cowled, Linfa Wang, Ashley Mansell, Paul Monaghan, Diane Green, Zhengli Shi, Michelle L. Baker
    Abstract:

    IRF7 in the Australian Black Flying Fox, Pteropus alecto - Table 1 : Evidence for a Unique Expression Pattern and Functional Conservation

Peng Zhou - One of the best experts on this subject based on the ideXlab platform.

  • Unlocking bat immunology: establishment of Pteropus alecto bone marrow-derived dendritic cells and macrophages
    Scientific reports, 2016
    Co-Authors: Peng Zhou, Yok Teng Chionh, Sergio Erdal Irac, Matae Ahn, Even Fossum, Bjarne Bogen, Florent Ginhoux, Aaron T. Irving, Charles-antoine Dutertre
    Abstract:

    Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages. Cells with the phenotype, morphology and functional features of monocyte-derived DC, bona fide DC or macrophages were obtained in GM-CSF/IL4, FLT3L or CSF-1 cultures, respectively. The successful generation of the first bat bone marrow-derived immune cells paves the way to unlocking the immune mechanisms that confer host resilience to pathogens in bats.

  • Contraction of the type I IFN locus and unusual constitutive expression of IFN-α in bats.
    Proceedings of the National Academy of Sciences of the United States of America, 2016
    Co-Authors: Peng Zhou, Ina Smith, Christopher Cowled, Mary Tachedjian, Lawrence Mok, James W. Wynne, Victoria Boyd, Jie Cui, Wojtek P. Michalski
    Abstract:

    Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-α loci. Furthermore, the three IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-α results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses.

  • characterisation of novel micrornas in the black flying fox Pteropus alecto by deep sequencing
    BMC Genomics, 2014
    Co-Authors: Christopher Cowled, Kristie A Jenkins, Mark Tizard, Pauline Cottee, Vladimir A Likic, Cameron R. Stewart, Mary Tachedjian, Glenn A. Marsh, Marc R Friedlander, Peng Zhou
    Abstract:

    Background: Bats are a major source of new and emerging viral diseases. Despite the fact that bats carry and shed highly pathogenic viruses including Ebola, Nipah and SARS, they rarely display clinical symptoms of infection. Host factors influencing viral replication are poorly understood in bats and are likely to include both pre- and post-transcriptional regulatory mechanisms. MicroRNAs are a major mechanism of post-transcriptional gene regulation, however very little is known about them in bats. Results: This study describes 399 microRNAs identified by deep sequencing of small RNA isolated from tissues of the Black flying fox, Pteropus alecto, a confirmed natural reservoir of the human pathogens Hendra virus and Australian bat lyssavirus. Of the microRNAs identified, more than 100 are unique amongst vertebrates, including a subset containing mutations in critical seed regions. Clusters of rapidly-evolving microRNAs were identified, as well as microRNAs predicted to target genes involved in antiviral immunity, the DNA damage response, apoptosis and autophagy. Closer inspection of the predicted targets for several highly supported novel miRNA candidates suggests putative roles in host-virus interaction. Conclusions: MicroRNAs are likely to play major roles in regulating virus-host interaction in bats, via dampening of inflammatory responses (limiting the effects of immunopathology), and directly limiting the extent of viral replication, either through restricting the availability of essential factors or by controlling apoptosis. Characterisation of the bat microRNA repertoire is an essential step towards understanding transcriptional regulation during viral infection, and will assist in the identification of mechanisms that enable bats to act as natural virus reservoirs. This in turn will facilitate the development of antiviral strategies for use in humans and other species.

  • IRF7 in the Australian Black Flying Fox, Pteropus alecto - Table 1 : Evidence for a Unique Expression Pattern and Functional Conservation
    2014
    Co-Authors: Peng Zhou, Christopher Cowled, Linfa Wang, Ashley Mansell, Paul Monaghan, Diane Green, Zhengli Shi, Michelle L. Baker
    Abstract:

    IRF7 in the Australian Black Flying Fox, Pteropus alecto - Table 1 : Evidence for a Unique Expression Pattern and Functional Conservation

  • IRF7 in the Australian Black Flying Fox, Pteropus alecto: Evidence for a Unique Expression Pattern and Functional Conservation
    2014
    Co-Authors: Peng Zhou, Christopher Cowled, Linfa Wang, Ashley Mansell, Paul Monaghan, Diane Green, Zhengli Shi, Michelle L. Baker
    Abstract:

    As the only flying mammal, bats harbor a number of emerging and re-emerging viruses, many of which cause severe diseases in humans and other mammals yet result in no clinical symptoms in bats. As the master regulator of the interferon (IFN)-dependent immune response, IFN regulatory factor 7 (IRF7) plays a central role in innate antiviral immunity. To explore the role of bat IRF7 in the regulation of the IFN response, we performed sequence and functional analysis of IRF7 from the pteropid bat, Pteropus alecto. Our results demonstrate that bat IRF7 retains the ability to bind to MyD88 and activate the IFN response despite unique changes in the MyD88 binding domain. We also demonstrate that bat IRF7 has a unique expression pattern across both immune and non-immune related tissues and is inducible by double-strand RNA. The broad tissue distribution of IRF7 may provide bats with an enhanced ability to rapidly activate the IFN response in a wider range of tissues compared to other mammals. The importance of IRF7 in antiviral activity against the bat reovirus, Pulau virus was confirmed by siRNA knockdown of IRF7 in bat cells resulting in enhanced viral replication. Our results highlight th