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Article ; Online: Chikungunya virus, risks and responses for Australia

Andreas Suhrbier / Greg Devine

Australian and New Zealand Journal of Public Health, Vol 40, Iss 3, Pp 207-

2016 Volume 209

Keywords	Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2016-06-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Widespread discrepancy in Nnt genotypes and genetic backgrounds complicates granzyme A and other knockout mouse studies

Daniel J Rawle / Thuy T Le / Troy Dumenil / Cameron Bishop / Kexin Yan / Eri Nakayama / Phillip I Bird / Andreas Suhrbier

eLife, Vol

2022 Volume 11

Abstract: Granzyme A (GZMA) is a serine protease secreted by cytotoxic lymphocytes, with Gzma-/- mouse studies having informed our understanding of GZMA’s physiological function. We show herein that Gzma-/- mice have a mixed C57BL/6J and C57BL/6N genetic ... ...

Abstract	Granzyme A (GZMA) is a serine protease secreted by cytotoxic lymphocytes, with Gzma-/- mouse studies having informed our understanding of GZMA’s physiological function. We show herein that Gzma-/- mice have a mixed C57BL/6J and C57BL/6N genetic background and retain the full-length nicotinamide nucleotide transhydrogenase (Nnt) gene, whereas Nnt is truncated in C57BL/6J mice. Chikungunya viral arthritis was substantially ameliorated in Gzma-/- mice; however, the presence of Nnt and the C57BL/6N background, rather than loss of GZMA expression, was responsible for this phenotype. A new CRISPR active site mutant C57BL/6J GzmaS211A mouse provided the first insights into GZMA’s bioactivity free of background issues, with circulating proteolytically active GZMA promoting immune-stimulating and pro-inflammatory signatures. Remarkably, k-mer mining of the Sequence Read Archive illustrated that ≈27% of Run Accessions and ≈38% of BioProjects listing C57BL/6J as the mouse strain had Nnt sequencing reads inconsistent with a C57BL/6J genetic background. Nnt and C57BL/6N background issues have clearly complicated our understanding of GZMA and may similarly have influenced studies across a broad range of fields.
Keywords	granzyme A ; nicotinamide nucleotide transhydrogenase ; chikungunya ; inflammation ; C57BL/6J ; C57BL/6N ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Chimeric Binjari-Zika Vaccine Provides Long-Term Protection against ZIKA Virus Challenge

Jessamine E. Hazlewood / Bing Tang / Kexin Yan / Daniel J. Rawle / Jessica J. Harrison / Roy A. Hall / Jody Hobson-Peters / Andreas Suhrbier

Vaccines, Vol 10, Iss 85, p

2022 Volume 85

Abstract: We recently developed a chimeric flavivirus vaccine technology based on the novel insect-specific Binjari virus (BinJV) and used this to generate a chimeric ZIKV vaccine (BinJ/ZIKA-prME) that protected IFNAR -/- dams and fetuses from infection. Herein, ... ...

Abstract	We recently developed a chimeric flavivirus vaccine technology based on the novel insect-specific Binjari virus (BinJV) and used this to generate a chimeric ZIKV vaccine (BinJ/ZIKA-prME) that protected IFNAR -/- dams and fetuses from infection. Herein, we show that a single vaccination of IFNAR -/- mice with unadjuvanted BinJ/ZIKA-prME generated neutralizing antibody responses that were retained for 14 months. At 15 months post vaccination, mice were also completely protected against detectable viremia and substantial body weight loss after challenge with ZIKV PRVABC59 . BinJ/ZIKA-prME vaccination thus provided long-term protective immunity without the need for adjuvant or replication of the vaccine in the vaccine recipient, both attractive features for a ZIKV vaccine.
Keywords	vaccine ; Binjari virus ; Zika virus ; mouse model ; insect-specific flavivirus ; chimeric virus ; Medicine ; R
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: ACE2-lentiviral transduction enables mouse SARS-CoV-2 infection and mapping of receptor interactions.

Daniel J Rawle / Thuy T Le / Troy Dumenil / Kexin Yan / Bing Tang / Wilson Nguyen / Daniel Watterson / Naphak Modhiran / Jody Hobson-Peters / Cameron Bishop / Andreas Suhrbier

PLoS Pathogens, Vol 17, Iss 7, p e

2021 Volume 1009723

Abstract: SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse ACE2 (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system and illustrate its utility for in vitro and in vivo SARS-CoV-2 infection ... ...

Abstract	SARS-CoV-2 uses the human ACE2 (hACE2) receptor for cell attachment and entry, with mouse ACE2 (mACE2) unable to support infection. Herein we describe an ACE2-lentivirus system and illustrate its utility for in vitro and in vivo SARS-CoV-2 infection models. Transduction of non-permissive cell lines with hACE2 imparted replication competence, and transduction with mACE2 containing N30D, N31K, F83Y and H353K substitutions, to match hACE2, rescued SARS-CoV-2 replication. Intrapulmonary hACE2-lentivirus transduction of C57BL/6J mice permitted significant virus replication in lung epithelium. RNA-Seq and histological analyses illustrated that this model involved an acute inflammatory disease followed by resolution and tissue repair, with a transcriptomic profile similar to that seen in COVID-19 patients. hACE2-lentivirus transduction of IFNAR-/- and IL-28RA-/- mouse lungs was used to illustrate that loss of type I or III interferon responses have no significant effect on virus replication. However, their importance in driving inflammatory responses was illustrated by RNA-Seq analyses. We also demonstrate the utility of the hACE2-lentivirus transduction system for vaccine evaluation in C57BL/6J mice. The ACE2-lentivirus system thus has broad application in SARS-CoV-2 research, providing a tool for both mutagenesis studies and mouse model development.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The dinucleotide composition of the Zika virus genome is shaped by conflicting evolutionary pressures in mammalian hosts and mosquito vectors.

Jelke J Fros / Imke Visser / Bing Tang / Kexin Yan / Eri Nakayama / Tessa M Visser / Constantianus J M Koenraadt / Monique M van Oers / Gorben P Pijlman / Andreas Suhrbier / Peter Simmonds

PLoS Biology, Vol 19, Iss 4, p e

2021 Volume 3001201

Abstract: Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition of host cell transcriptomes. In contrast, CpG suppression is absent in both invertebrate mRNA and RNA viruses that ... ...

Abstract	Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition of host cell transcriptomes. In contrast, CpG suppression is absent in both invertebrate mRNA and RNA viruses that exclusively infect arthropods. Arthropod-borne (arbo) viruses are transmitted between vertebrate hosts by invertebrate vectors and thus encounter potentially conflicting evolutionary pressures in the different cytoplasmic environments. Using a newly developed Zika virus (ZIKV) model, we have investigated how demands for CpG suppression in vertebrate cells can be reconciled with potentially quite different compositional requirements in invertebrates and how this affects ZIKV replication and transmission. Mutant viruses with synonymously elevated CpG or UpA dinucleotide frequencies showed attenuated replication in vertebrate cell lines, which was rescued by knockout of the zinc-finger antiviral protein (ZAP). Conversely, in mosquito cells, ZIKV mutants with elevated CpG dinucleotide frequencies showed substantially enhanced replication compared to wild type. Host-driven effects on virus replication attenuation and enhancement were even more apparent in mouse and mosquito models. Infections with CpG- or UpA-high ZIKV mutants in mice did not cause typical ZIKV-induced tissue damage and completely protected mice during subsequent challenge with wild-type virus, which demonstrates their potential as live-attenuated vaccines. In contrast, the CpG-high mutants displayed enhanced replication in Aedes aegypti mosquitoes and a larger proportion of mosquitoes carried infectious virus in their saliva. These findings show that mosquito cells are also capable of discriminating RNA based on dinucleotide composition. However, the evolutionary pressure on the CpG dinucleotides of viral genomes in arthropod vectors directly opposes the pressure present in vertebrate host cells, which provides evidence that an adaptive compromise is required for arbovirus transmission. This suggests that ...
Keywords	Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Zika Vaccine Generated Using the Chimeric Insect-Specific Binjari Virus Platform Protects against Fetal Brain Infection in Pregnant Mice

Jessamine E. Hazlewood / Daniel J. Rawle / Bing Tang / Kexin Yan / Laura J. Vet / Eri Nakayama / Jody Hobson-Peters / Roy A. Hall / Andreas Suhrbier

Vaccines, Vol 8, Iss 496, p

2020 Volume 496

Abstract: Zika virus (ZIKV) is the etiological agent of congenital Zika syndrome (CZS), a spectrum of birth defects that can lead to life-long disabilities. A range of vaccines are in development with the target population including pregnant women and women of ... ...

Abstract	Zika virus (ZIKV) is the etiological agent of congenital Zika syndrome (CZS), a spectrum of birth defects that can lead to life-long disabilities. A range of vaccines are in development with the target population including pregnant women and women of child-bearing age. Using a recently described chimeric flavivirus vaccine technology based on the novel insect-specific Binjari virus (BinJV), we generated a ZIKV vaccine (BinJ/ZIKA-prME) and illustrate herein its ability to protect against fetal brain infection. Female IFNAR −/− mice were vaccinated once with unadjuvanted BinJ/ZIKA-prME, were mated, and at embryonic day 12.5 were challenged with ZIKV PRVABC59 . No infectious ZIKV was detected in maternal blood, placenta, or fetal heads in BinJ/ZIKA-prME-vaccinated mice. A similar result was obtained when the more sensitive qRT PCR methodology was used to measure the viral RNA. BinJ/ZIKA-prME vaccination also did not result in antibody-dependent enhancement of dengue virus infection or disease. BinJ/ZIKA-prME thus emerges as a potential vaccine candidate for the prevention of CSZ.
Keywords	vaccine ; Binjari ; Zika ; dengue ; mouse model ; Medicine ; R
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Yellow Fever Virus 17D Infection and Disease Mouse Model Used to Evaluate a Chimeric Binjari-Yellow Fever Virus Vaccine

Kexin Yan / Laura J. Vet / Bing Tang / Jody Hobson-Peters / Daniel J. Rawle / Thuy T. Le / Thibaut Larcher / Roy A. Hall / Andreas Suhrbier

Vaccines, Vol 8, Iss 368, p

2020 Volume 368

Abstract: Despite the availability of an effective, live attenuated yellow fever virus (YFV) vaccine (YFV 17D), this flavivirus still causes up to ≈60,000 deaths annually. A number of new approaches are seeking to address vaccine supply issues and improve safety ... ...

Abstract	Despite the availability of an effective, live attenuated yellow fever virus (YFV) vaccine (YFV 17D), this flavivirus still causes up to ≈60,000 deaths annually. A number of new approaches are seeking to address vaccine supply issues and improve safety for the immunocompromised vaccine recipients. Herein we describe an adult female IFNAR-/- mouse model of YFV 17D infection and disease that recapitulates many features of infection and disease in humans. We used this model to evaluate a new YFV vaccine that is based on a recently described chimeric Binjari virus (BinJV) vaccine technology. BinJV is an insect-specific flavivirus and the chimeric YFV vaccine (BinJ/YFV-prME) was generated by replacing the prME genes of BinJV with the prME genes of YFV 17D. Such BinJV chimeras retain their ability to replicate to high titers in C6/36 mosquito cells (allowing vaccine production), but are unable to replicate in vertebrate cells. Vaccination with adjuvanted BinJ/YFV-prME induced neutralizing antibodies and protected mice against infection, weight loss and liver pathology after YFV 17D challenge.
Keywords	yellow fever virus ; mouse model ; vaccine ; Binjari virus ; Medicine ; R
Subject code	570
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sequencing of Historical Isolates, K-mer Mining and High Serological Cross-Reactivity with Ross River Virus Argue against the Presence of Getah Virus in Australia

Daniel J. Rawle / Wilson Nguyen / Troy Dumenil / Rhys Parry / David Warrilow / Bing Tang / Thuy T. Le / Andrii Slonchak / Alexander A. Khromykh / Viviana P. Lutzky / Kexin Yan / Andreas Suhrbier

Pathogens, Vol 9, Iss 848, p

2020 Volume 848

Abstract: Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original ... ...

Abstract	Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original isolates (N544 and N554), illustrated that these viruses were virtually identical to the 1955 GETV MM2021 isolate from Malaysia. K-mer mining of the >40,000 terabases of sequence data in the Sequence Read Archive followed by BLASTn confirmation identified multiple GETV sequences in biosamples from Asia (often as contaminants), but not in biosamples from Australia. In contrast, sequence reads aligning to the Australian Ross River virus (RRV) were readily identified in Australian biosamples. To explore the serological relationship between GETV and other alphaviruses, an adult wild-type mouse model of GETV was established. High levels of cross-reactivity and cross-protection were evident for convalescent sera from mice infected with GETV or RRV, highlighting the difficulties associated with the interpretation of early serosurveys reporting GETV antibodies in Australian cattle and pigs. The evidence that GETV circulates in Australia is thus not compelling.
Keywords	Getah virus ; Ross River virus ; Sequence Read Archive ; serology ; mouse model ; virus contamination ; Medicine ; R
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures.

Jessamine E Hazlewood / Troy Dumenil / Thuy T Le / Andrii Slonchak / Stephen H Kazakoff / Ann-Marie Patch / Lesley-Ann Gray / Paul M Howley / Liang Liu / John D Hayball / Kexin Yan / Daniel J Rawle / Natalie A Prow / Andreas Suhrbier

PLoS Pathogens, Vol 17, Iss 1, p e

2021 Volume 1009215

Abstract: Poxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, ... ...

Abstract	Poxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, as well as expression of vector and recombinant immunogen genes, after vaccination with a new multiplication defective, vaccinia-based vector, Sementis Copenhagen Vector. Chikungunya and Zika virus immunogen mRNA and protein expression was associated with necrosing skeletal muscle cells surrounded by mixed cellular infiltrates. The multiple adjuvant signatures at 12 hours post-vaccination were dominated by TLR3, 4 and 9, STING, MAVS, PKR and the inflammasome. Th1 cytokine signatures were dominated by IFNγ, TNF and IL1β, and chemokine signatures by CCL5 and CXCL12. Multiple signatures associated with dendritic cell stimulation were evident. By day seven, vaccine transcripts were absent, and cell death, neutrophil, macrophage and inflammation annotations had abated. No compelling arthritis signatures were identified. Such injection site vaccinology approaches should inform refinements in poxvirus-based vector design.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Temperature modulates immune gene expression in mosquitoes during arbovirus infection

B. M. C. Randika Wimalasiri-Yapa / Roberto A. Barrero / Liesel Stassen / Louise M. Hafner / Elizabeth A. McGraw / Alyssa T. Pyke / Cassie C. Jansen / Andreas Suhrbier / Laith Yakob / Wenbiao Hu / Gregor J. Devine / Francesca D. Frentiu

Open Biology, Vol 11, Iss

2021 Volume 1

Abstract: The principal vector of dengue, Zika and chikungunya viruses is the mosquito Aedes aegypti, with its ability to transmit pathogens influenced by ambient temperature. We use chikungunya virus (CHIKV) to understand how the mosquito transcriptome responds ... ...

Abstract	The principal vector of dengue, Zika and chikungunya viruses is the mosquito Aedes aegypti, with its ability to transmit pathogens influenced by ambient temperature. We use chikungunya virus (CHIKV) to understand how the mosquito transcriptome responds to arbovirus infection at different ambient temperatures. We exposed CHIKV-infected mosquitoes to 18, 28 and 32°C, and found that higher temperature correlated with higher virus levels, particularly at 3 days post infection, but lower temperature resulted in reduced virus levels. RNAseq analysis indicated significantly altered gene expression levels in CHIKV infection. The highest number of significantly differentially expressed genes was observed at 28°C, with a more muted effect at the other temperatures. At the higher temperature, the expression of many classical immune genes, including Dicer-2, was not substantially altered in response to CHIKV. The upregulation of Toll, IMD and JAK-STAT pathways was only observed at 28°C. Functional annotations suggested that genes in immune response and metabolic pathways related to energy supply and DNA replication were involved in temperature-dependent changes. Time post infection also led to substantially different gene expression profiles, and this varied with temperature. In conclusion, temperature significantly modulates mosquito gene expression in response to infection, potentially leading to impairment of immune defences at higher temperatures.
Keywords	aedes aegypti ; transcriptome ; temperature ; chikungunya virus ; immune genes ; rna seq ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	The Royal Society
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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