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Article ; Online: Antiviral effects of interferon-stimulated genes in bats.

Zhang, Dan / Irving, Aaron T

Frontiers in cellular and infection microbiology

2023 Volume 13, Page(s) 1224532

Abstract: The interferon pathway is the first line of defense in viral infection in all mammals, and its induction stimulates broad expression of interferon-stimulated genes (ISGs). In mice and also humans, the antiviral function of ISGs has been extensively ... ...

Abstract	The interferon pathway is the first line of defense in viral infection in all mammals, and its induction stimulates broad expression of interferon-stimulated genes (ISGs). In mice and also humans, the antiviral function of ISGs has been extensively studied. As an important viral reservoir in nature, bats can coexist with a variety of pathogenic viruses without overt signs of disease, yet only limited data are available for the role of ISGs in bats. There are multiple species of bats and work has begun deciphering the differences and similarities between ISG function of human/mouse and different bat species. This review summarizes the current knowledge of conserved and bat-specific-ISGs and their known antiviral effector functions.
MeSH term(s)	Humans ; Animals ; Mice ; Antiviral Agents ; Interferons ; Chiroptera
Chemical Substances	Antiviral Agents ; Interferons (9008-11-1)
Language	English
Publishing date	2023-08-18
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1224532
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Article ; Online: Massively-multiplexed epitope mapping techniques for viral antigen discovery.

Hu, Diya / Irving, Aaron T

Frontiers in immunology

2023 Volume 14, Page(s) 1192385

Abstract: Following viral infection, viral antigens bind specifically to receptors on the surface of lymphocytes thereby activating adaptive immunity in the host. An epitope, the smallest structural and functional unit of an antigen, binds specifically to an ... ...

Abstract	Following viral infection, viral antigens bind specifically to receptors on the surface of lymphocytes thereby activating adaptive immunity in the host. An epitope, the smallest structural and functional unit of an antigen, binds specifically to an antibody or antigen receptor, to serve as key sites for the activation of adaptive immunity. The complexity and diverse range of epitopes are essential to study and map for the diagnosis of disease, the design of vaccines and for immunotherapy. Mapping the location of these specific epitopes has become a hot topic in immunology and immune therapy. Recently, epitope mapping techniques have evolved to become multiplexed, with the advent of high-throughput sequencing and techniques such as bacteriophage-display libraries and deep mutational scanning. Here, we briefly introduce the principles, advantages, and disadvantages of the latest epitope mapping techniques with examples for viral antigen discovery.
MeSH term(s)	Epitope Mapping/methods ; Antigens, Viral ; Epitopes ; Antigens ; Cell Surface Display Techniques/methods
Chemical Substances	Antigens, Viral ; Epitopes ; Antigens
Language	English
Publishing date	2023-09-25
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1192385
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Article ; Online: The translational potential of studying bat immunity.

Baid, Kaushal / Irving, Aaron T / Jouvenet, Nolwenn / Banerjee, Arinjay

Trends in immunology

2024 Volume 45, Issue 3, Page(s) 188–197

Abstract: Molecular studies in bats have led to the discovery of antiviral adaptations that may explain how some bat species have evolved enhanced immune tolerance towards viruses. Accumulating data suggest that some bat species have also evolved remarkable ... ...

Abstract	Molecular studies in bats have led to the discovery of antiviral adaptations that may explain how some bat species have evolved enhanced immune tolerance towards viruses. Accumulating data suggest that some bat species have also evolved remarkable features of longevity and low rates of cancer. Furthermore, recent research strongly suggests that discovering immune adaptations in bat models can be translated to develop immune modulators and recognize alternate therapeutic strategies for diseases affecting humans. We posit that research in bat immunology will lead to discoveries that can potentially be translated to improve health outcomes in humans.
MeSH term(s)	Animals ; Humans ; Chiroptera ; Viruses
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2024.01.007
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Article ; Online: Unraveling the Zoonotic Origin and Transmission of SARS-CoV-2.

Banerjee, Arinjay / Doxey, Andrew C / Mossman, Karen / Irving, Aaron T

Trends in ecology & evolution

2020 Volume 36, Issue 3, Page(s) 180–184

Abstract: The origin and zoonotic transmission route of SARS-CoV-2 remain speculative. We discuss scenarios for the zoonotic emergence of SARS-CoV-2, and also explore the missing evidence and ecological considerations that are necessary to confidently identify the ...

Abstract	The origin and zoonotic transmission route of SARS-CoV-2 remain speculative. We discuss scenarios for the zoonotic emergence of SARS-CoV-2, and also explore the missing evidence and ecological considerations that are necessary to confidently identify the origin and transmission route of SARS-CoV-2 and to prevent future pandemics of zoonotic viruses.
MeSH term(s)	Animals ; COVID-19 ; Humans ; Pandemics ; SARS-CoV-2 ; Zoonoses/epidemiology
Language	English
Publishing date	2020-12-13
Publishing country	England
Document type	Journal Article
ZDB-ID	284965-3
ISSN	1872-8383 ; 0169-5347
ISSN (online)	1872-8383
ISSN	0169-5347
DOI	10.1016/j.tree.2020.12.002
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Article ; Online: Lessons from the host defences of bats, a unique viral reservoir.

Irving, Aaron T / Ahn, Matae / Goh, Geraldine / Anderson, Danielle E / Wang, Lin-Fa

Nature

2021 Volume 589, Issue 7842, Page(s) 363–370

Abstract: There have been several major outbreaks of emerging viral diseases, including Hendra, Nipah, Marburg and Ebola virus diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)-as well as the current pandemic of ... ...

Abstract	There have been several major outbreaks of emerging viral diseases, including Hendra, Nipah, Marburg and Ebola virus diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)-as well as the current pandemic of coronavirus disease 2019 (COVID-19). Notably, all of these outbreaks have been linked to suspected zoonotic transmission of bat-borne viruses. Bats-the only flying mammal-display several additional features that are unique among mammals, such as a long lifespan relative to body size, a low rate of tumorigenesis and an exceptional ability to host viruses without presenting clinical disease. Here we discuss the mechanisms that underpin the host defence system and immune tolerance of bats, and their ramifications for human health and disease. Recent studies suggest that 64 million years of adaptive evolution have shaped the host defence system of bats to balance defence and tolerance, which has resulted in a unique ability to act as an ideal reservoir host for viruses. Lessons from the effective host defence of bats would help us to better understand viral evolution and to better predict, prevent and control future viral spillovers. Studying the mechanisms of immune tolerance in bats could lead to new approaches to improving human health. We strongly believe that it is time to focus on bats in research for the benefit of both bats and humankind.
MeSH term(s)	Animals ; Asymptomatic Diseases ; Chiroptera/immunology ; Chiroptera/virology ; Disease Reservoirs/veterinary ; Disease Reservoirs/virology ; Evolution, Molecular ; Humans ; Immune Tolerance ; Viral Zoonoses/immunology ; Viral Zoonoses/transmission ; Viral Zoonoses/virology
Language	English
Publishing date	2021-01-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-020-03128-0
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Article: Unraveling the Zoonotic Origin and Transmission of SARS-CoV-2

Banerjee, Arinjay / Doxey, Andrew C / Mossman, Karen / Irving, Aaron T

Trends in ecology & evolution. 2021 Mar., v. 36, no. 3

2021

Abstract	The origin and zoonotic transmission route of SARS-CoV-2 remain speculative. We discuss scenarios for the zoonotic emergence of SARS-CoV-2, and also explore the missing evidence and ecological considerations that are necessary to confidently identify the origin and transmission route of SARS-CoV-2 and to prevent future pandemics of zoonotic viruses.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; ecology ; evolution
Language	English
Dates of publication	2021-03
Size	p. 180-184.
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	284965-3
ISSN	1872-8383 ; 0169-5347
ISSN (online)	1872-8383
ISSN	0169-5347
DOI	10.1016/j.tree.2020.12.002
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Article ; Online: Applications of VirScan to broad serological profiling of bat reservoirs for emerging zoonoses.

Ruhs, Emily Cornelius / Chia, Wan Ni / Foo, Randy / Peel, Alison J / Li, Yimei / Larman, H Benjamin / Irving, Aaron T / Wang, Linfa / Brook, Cara E

Frontiers in public health

2023 Volume 11, Page(s) 1212018

Abstract: Introduction: Bats are important providers of ecosystem services such as pollination, seed dispersal, and insect control but also act as natural reservoirs for virulent zoonotic viruses. Bats host multiple viruses that cause life-threatening pathology ... ...

Abstract	Introduction: Bats are important providers of ecosystem services such as pollination, seed dispersal, and insect control but also act as natural reservoirs for virulent zoonotic viruses. Bats host multiple viruses that cause life-threatening pathology in other animals and humans but, themselves, experience limited pathological disease from infection. Despite bats' importance as reservoirs for several zoonotic viruses, we know little about the broader viral diversity that they host. Bat virus surveillance efforts are challenged by difficulties of field capture and the limited scope of targeted PCR- or ELISA-based molecular and serological detection. Additionally, virus shedding is often transient, thus also limiting insights gained from nucleic acid testing of field specimens. Phage ImmunoPrecipitation Sequencing (PhIP-Seq), a broad serological tool used previously to comprehensively profile viral exposure history in humans, offers an exciting prospect for viral surveillance efforts in wildlife, including bats. Methods: Here, for the first time, we apply PhIP-Seq technology to bat serum, using a viral peptide library originally designed to simultaneously assay exposures to the entire human virome. Results: Using VirScan, we identified past exposures to 57 viral genera-including betacoronaviruses, henipaviruses, lyssaviruses, and filoviruses-in semi-captive Discussion: Overall, our work emphasizes the utility of applying biomedical tools, like PhIP-Seq, first developed for humans to viral surveillance efforts in wildlife, while highlighting opportunities for taxon-specific improvements.
MeSH term(s)	Animals ; Humans ; Disease Reservoirs ; Ecosystem ; Seroepidemiologic Studies ; Zoonoses ; Chiroptera
Language	English
Publishing date	2023-09-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2023.1212018
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Article ; Online: Unique Evolution of Antiviral Tetherin in Bats.

Hayward, Joshua A / Tachedjian, Mary / Johnson, Adam / Irving, Aaron T / Gordon, Tamsin B / Cui, Jie / Nicolas, Alexis / Smith, Ina / Boyd, Victoria / Marsh, Glenn A / Baker, Michelle L / Wang, Lin-Fa / Tachedjian, Gilda

Journal of virology

2022 Volume 96, Issue 20, Page(s) e0115222

Abstract: Bats are recognized as important reservoirs of viruses deadly to other mammals, including humans. These infections are typically nonpathogenic in bats, raising questions about host response differences that might exist between bats and other mammals. ... ...

Abstract	Bats are recognized as important reservoirs of viruses deadly to other mammals, including humans. These infections are typically nonpathogenic in bats, raising questions about host response differences that might exist between bats and other mammals. Tetherin is a restriction factor which inhibits the release of a diverse range of viruses from host cells, including retroviruses, coronaviruses, filoviruses, and paramyxoviruses, some of which are deadly to humans and transmitted by bats. Here, we characterize the tetherin genes from 27 bat species, revealing that they have evolved under strong selective pressure, and that fruit bats and vesper bats express unique structural variants of the tetherin protein. Tetherin was widely and variably expressed across fruit bat tissue types and upregulated in spleen tissue when stimulated with Toll-like receptor agonists. The expression of two computationally predicted splice isoforms of fruit bat tetherin was verified. We identified an additional third unique splice isoform which includes a C-terminal region that is not homologous to known mammalian tetherin variants but was functionally capable of restricting the release of filoviral virus-like particles. We also report that vesper bats possess and express at least five tetherin genes, including structural variants, more than any other mammal reported to date. These findings support the hypothesis of differential antiviral gene evolution in bats relative to other mammals.
MeSH term(s)	Humans ; Animals ; Bone Marrow Stromal Antigen 2/genetics ; Chiroptera ; Antiviral Agents ; Viruses ; Virus Diseases ; Toll-Like Receptors
Chemical Substances	Bone Marrow Stromal Antigen 2 ; Antiviral Agents ; Toll-Like Receptors
Language	English
Publishing date	2022-09-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01152-22
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Article ; Online: Positive Selection of a Serine Residue in Bat IRF3 Confers Enhanced Antiviral Protection.

Banerjee, Arinjay / Zhang, Xi / Yip, Alyssa / Schulz, Katharina S / Irving, Aaron T / Bowdish, Dawn / Golding, Brian / Wang, Lin-Fa / Mossman, Karen

iScience

2020 Volume 23, Issue 3, Page(s) 100958

Abstract: Compared with other mammals, bats harbor more zoonotic viruses per species and do not demonstrate signs of disease on infection with these viruses. To counteract infections with viruses, bats have evolved enhanced mechanisms to limit virus replication ... ...

Abstract	Compared with other mammals, bats harbor more zoonotic viruses per species and do not demonstrate signs of disease on infection with these viruses. To counteract infections with viruses, bats have evolved enhanced mechanisms to limit virus replication and immunopathology. However, molecular and cellular drivers of antiviral responses in bats largely remain an enigma. In this study, we demonstrate that a serine residue in IRF3 is positively selected for in multiple bat species. IRF3 is a central regulator of innate antiviral responses in mammals. Replacing the serine residue in bat IRF3 with the human leucine residue decreased antiviral protection in bat cells, whereas the addition of this serine residue in human IRF3 significantly enhanced antiviral protection in human cells. Our study provides genetic and functional evidence for enhanced IRF3-mediated antiviral responses in bats and adds support to speculations that bats have positively selected for multiple adaptations in their antiviral immune responses.
Keywords	covid19
Language	English
Publishing date	2020-03-02
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2020.100958
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Article ; Online: Complementary regulation of caspase-1 and IL-1β reveals additional mechanisms of dampened inflammation in bats.

Goh, Geraldine / Ahn, Matae / Zhu, Feng / Lee, Lim Beng / Luo, Dahai / Irving, Aaron T / Wang, Lin-Fa

Proceedings of the National Academy of Sciences of the United States of America

2020 Volume 117, Issue 46, Page(s) 28939–28949

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 ...

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
MeSH term(s)	Animals ; Caspase 1/metabolism ; Chiroptera/genetics ; Chiroptera/immunology ; Cytokines/metabolism ; DNA ; DNA-Binding Proteins ; HEK293 Cells ; Humans ; Inflammasomes/metabolism ; Inflammation/metabolism ; Interleukin-1beta/metabolism ; Macrophages/metabolism ; Pyroptosis ; Signal Transduction
Chemical Substances	AIM2 protein, human ; Cytokines ; DNA-Binding Proteins ; Inflammasomes ; Interleukin-1beta ; DNA (9007-49-2) ; Caspase 1 (EC 3.4.22.36)
Language	English
Publishing date	2020-10-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2003352117
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