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Article ; Online: Detection of SARS-CoV-2 infection by microRNA profiling of the upper respiratory tract.

Ryan J Farr / Christina L Rootes / John Stenos / Chwan Hong Foo / Christopher Cowled / Cameron R Stewart

PLoS ONE, Vol 17, Iss 4, p e

2022 Volume 0265670

Abstract: Host biomarkers are increasingly being considered as tools for improved COVID-19 detection and prognosis. We recently profiled circulating host-encoded microRNA (miRNAs) during SARS-CoV-2 infection, revealing a signature that classified COVID-19 cases ... ...

Abstract	Host biomarkers are increasingly being considered as tools for improved COVID-19 detection and prognosis. We recently profiled circulating host-encoded microRNA (miRNAs) during SARS-CoV-2 infection, revealing a signature that classified COVID-19 cases with 99.9% accuracy. Here we sought to develop a signature suited for clinical application by analyzing specimens collected using minimally invasive procedures. Eight miRNAs displayed altered expression in anterior nasal tissues from COVID-19 patients, with miR-142-3p, a negative regulator of interleukin-6 (IL-6) production, the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-30c-2-3p, miR-628-3p and miR-93-5p) independently classifies COVID-19 cases with 100% accuracy. This study further defines the host miRNA response to SARS-CoV-2 infection and identifies candidate biomarkers for improved COVID-19 detection.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
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: MicroRNA Biomarkers for Infectious Diseases

Leon Tribolet / Emily Kerr / Christopher Cowled / Andrew G. D. Bean / Cameron R. Stewart / Megan Dearnley / Ryan J. Farr

Frontiers in Microbiology, Vol

From Basic Research to Biosensing

2020 Volume 11

Abstract: In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18–22 nucleotide), non-coding RNA transcripts called microRNAs (miRNAs) have emerged as promising ... ...

Abstract	In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18–22 nucleotide), non-coding RNA transcripts called microRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential, due to their role in numerous diseases, previously established methods for quantitation and their stability within biofluids. Despite efforts to identify, characterize and apply miRNA signatures as diagnostic markers in a range of non-infectious diseases, their application in infectious disease has advanced relatively slowly. Here, we outline the benefits that miRNA biomarkers offer to the diagnosis, management, and treatment of infectious diseases. Investigation of these novel biomarkers could advance the use of personalized medicine in infectious disease treatment, which raises important considerations for validating their use as diagnostic or prognostic markers. Finally, we discuss new and emerging miRNA detection platforms, with a focus on rapid, point-of-care testing, to evaluate the benefits and obstacles of miRNA biomarkers for infectious disease.
Keywords	microRNAs ; infectious disease ; diagnostics ; biomarkers ; personalized medicine ; Microbiology ; QR1-502
Subject code	630 ; 610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ribosome-Profiling Reveals Restricted Post Transcriptional Expression of Antiviral Cytokines and Transcription Factors during SARS-CoV-2 Infection

Marina R. Alexander / Aaron M. Brice / Petrus Jansen van Vuren / Christina L. Rootes / Leon Tribolet / Christopher Cowled / Andrew G. D. Bean / Cameron R. Stewart

International Journal of Molecular Sciences, Vol 22, Iss 3392, p

2021 Volume 3392

Abstract: The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so understanding the host response is paramount. ... ...

Abstract	The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so understanding the host response is paramount. Transcriptomics has become incredibly important in understanding host-pathogen interactions; however, post-transcriptional regulation plays an important role in infection and immunity through translation and mRNA stability, allowing tight control over potent host responses by both the host and the invading virus. Here, we apply ribosome profiling to assess post-transcriptional regulation of host genes during SARS-CoV-2 infection of a human lung epithelial cell line (Calu-3). We have identified numerous transcription factors (JUN, ZBTB20, ATF3, HIVEP2 and EGR1) as well as select antiviral cytokine genes, namely IFNB1, IFNL1,2 and 3, IL-6 and CCL5, that are restricted at the post-transcriptional level by SARS-CoV-2 infection and discuss the impact this would have on the host response to infection. This early phase restriction of antiviral transcripts in the lungs may allow high viral load and consequent immune dysregulation typically seen in SARS-CoV-2 infection.
Keywords	SARS-CoV-2 ; ribosome profiling ; translation ; interferon ; cytokines ; transcriptome ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular characterisation of ILRUN, a novel inhibitor of proinflammatory and antimicrobial cytokines

Rebecca L. Ambrose / Aaron M. Brice / Alessandro T. Caputo / Marina R. Alexander / Leon Tribolet / Yu Chih Liu / Timothy E. Adams / Andrew G.D. Bean / Cameron R. Stewart

Heliyon, Vol 6, Iss 6, Pp e04115- (2020)

2020

Abstract: Regulation of type-I interferon (IFN) production is essential to the balance between antimicrobial defence and autoimmune disorders. The human protein-coding gene ILRUN (inflammation and lipid regulator with UBA-like and NBR1-like domains, previously ... ...

Abstract	Regulation of type-I interferon (IFN) production is essential to the balance between antimicrobial defence and autoimmune disorders. The human protein-coding gene ILRUN (inflammation and lipid regulator with UBA-like and NBR1-like domains, previously C6orf106) was recently characterised as an inhibitor of antiviral and proinflammatory cytokine (interferon-alpha/beta and tumor necrosis factor alpha) transcription. Currently there is a paucity of information about the molecular characteristics of ILRUN, despite it being associated with several diseases including virus infection, coronary artery disease, obesity and cancer. Here, we characterise ILRUN as a highly phylogenetically conserved protein containing UBA-like and a NBR1-like domains that are both essential for inhibition of type-I interferon and tumor necrosis factor alpha) transcription in human cells. We also solved the crystal structure of the NBR1-like domain, providing insights into its potential role in ILRUN function. This study provides critical information for future investigations into the role of ILRUN in health and disease.
Keywords	Immunolgy ; Inflammation ; Infectious disease ; Immune response ; Viruses ; Biochemistry ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Altered microRNA expression in COVID-19 patients enables identification of SARS-CoV-2 infection.

Ryan J Farr / Christina L Rootes / Louise C Rowntree / Thi H O Nguyen / Luca Hensen / Lukasz Kedzierski / Allen C Cheng / Katherine Kedzierska / Gough G Au / Glenn A Marsh / Seshadri S Vasan / Chwan Hong Foo / Christopher Cowled / Cameron R Stewart

PLoS Pathogens, Vol 17, Iss 7, p e

2021 Volume 1009759

Abstract: The host response to SARS-CoV-2 infection provide insights into both viral pathogenesis and patient management. The host-encoded microRNA (miRNA) response to SARS-CoV-2 infection, however, remains poorly defined. Here we profiled circulating miRNAs from ... ...

Abstract	The host response to SARS-CoV-2 infection provide insights into both viral pathogenesis and patient management. The host-encoded microRNA (miRNA) response to SARS-CoV-2 infection, however, remains poorly defined. Here we profiled circulating miRNAs from ten COVID-19 patients sampled longitudinally and ten age and gender matched healthy donors. We observed 55 miRNAs that were altered in COVID-19 patients during early-stage disease, with the inflammatory miR-31-5p the most strongly upregulated. Supervised machine learning analysis revealed that a three-miRNA signature (miR-423-5p, miR-23a-3p and miR-195-5p) independently classified COVID-19 cases with an accuracy of 99.9%. In a ferret COVID-19 model, the three-miRNA signature again detected SARS-CoV-2 infection with 99.7% accuracy, and distinguished SARS-CoV-2 infection from influenza A (H1N1) infection and healthy controls with 95% accuracy. Distinct miRNA profiles were also observed in COVID-19 patients requiring oxygenation. This study demonstrates that SARS-CoV-2 infection induces a robust host miRNA response that could improve COVID-19 detection and patient management.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
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 Troublesome Ticks Research Protocol

Pathogens, Vol 11, Iss 1290, p

Developing a Comprehensive, Multidiscipline Research Plan for Investigating Human Tick-Associated Disease in Australia

2022 Volume 1290

Abstract: In Australia, there is a paucity of data about the extent and impact of zoonotic tick-related illnesses. Even less is understood about a multifaceted illness referred to as Debilitating Symptom Complexes Attributed to Ticks (DSCATT). Here, we describe a ... ...

Abstract	In Australia, there is a paucity of data about the extent and impact of zoonotic tick-related illnesses. Even less is understood about a multifaceted illness referred to as Debilitating Symptom Complexes Attributed to Ticks (DSCATT). Here, we describe a research plan for investigating the aetiology, pathophysiology, and clinical outcomes of human tick-associated disease in Australia. Our approach focuses on the transmission of potential pathogens and the immunological responses of the patient after a tick bite. The protocol is strengthened by prospective data collection, the recruitment of two external matched control groups, and sophisticated integrative data analysis which, collectively, will allow the robust demonstration of associations between a tick bite and the development of clinical and pathological abnormalities. Various laboratory analyses are performed including metagenomics to investigate the potential transmission of bacteria, protozoa and/or viruses during tick bite. In addition, multi-omics technology is applied to investigate links between host immune responses and potential infectious and non-infectious disease causations. Psychometric profiling is also used to investigate whether psychological attributes influence symptom development. This research will fill important knowledge gaps about tick-borne diseases. Ultimately, we hope the results will promote improved diagnostic outcomes, and inform the safe management and treatment of patients bitten by ticks in Australia.
Keywords	DSCATT ; ticks ; tick-borne infection ; tick-borne disease ; Lyme disease-like illness ; biomarkers ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immunostimulatory motifs enhance antiviral siRNAs targeting highly pathogenic avian influenza H5N1.

Cameron R Stewart / Adam J Karpala / Sue Lowther / John W Lowenthal / Andrew G Bean

PLoS ONE, Vol 6, Iss 7, p e

2011 Volume 21552

Abstract: Highly pathogenic avian influenza (HPAI) H5N1 virus is endemic in many regions around the world and remains a significant pandemic threat. To date H5N1 has claimed almost 300 human lives worldwide, with a mortality rate of 60% and has caused the death or ...

Abstract	Highly pathogenic avian influenza (HPAI) H5N1 virus is endemic in many regions around the world and remains a significant pandemic threat. To date H5N1 has claimed almost 300 human lives worldwide, with a mortality rate of 60% and has caused the death or culling of hundreds of millions of poultry since its initial outbreak in 1997. We have designed multi-functional RNA interference (RNAi)-based therapeutics targeting H5N1 that degrade viral mRNA via the RNAi pathway while at the same time augmenting the host antiviral response by inducing host type I interferon (IFN) production. Moreover, we have identified two factors critical for maximising the immunostimulatory properties of short interfering (si)RNAs in chicken cells (i) mode of synthesis and (ii) nucleoside sequence to augment the response to virus. The 5-bp nucleoside sequence 5'-UGUGU-3' is a key determinant in inducing high levels of expression of IFN-α, -β, -λ and interleukin 1-β in chicken cells. Positioning of this 5'-UGUGU-3' motif at the 5'-end of the sense strand of siRNAs, but not the 3'-end, resulted in a rapid and enhanced induction of type I IFN. An anti-H5N1 avian influenza siRNA directed against the PB1 gene (PB1-2257) tagged with 5'-UGUGU-3' induced type I IFN earlier and to a greater extent compared to a non-tagged PB1-2257. Tested against H5N1 in vitro, the tagged PB1-2257 was more effective than non-tagged PB1-2257. These data demonstrate the ability of an immunostimulatory motif to improve the performance of an RNAi-based antiviral, a finding that may influence the design of future RNAi-based anti-influenza therapeutics.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2011-01-01T00:00:00Z
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: Circulating microRNA profiles of Hendra virus infection in horses

Christopher Cowled / Chwan-Hong Foo / Celine Deffrasnes / Christina L. Rootes / David T. Williams / Deborah Middleton / Lin-Fa Wang / Andrew G. D. Bean / Cameron R. Stewart

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 10

Abstract: Abstract Hendra virus (HeV) is an emerging zoonotic pathogen harbored by Australian mainland flying foxes. HeV infection can cause lethal disease in humans and horses, and to date all cases of human HeV disease have resulted from contact with infected ... ...

Abstract	Abstract Hendra virus (HeV) is an emerging zoonotic pathogen harbored by Australian mainland flying foxes. HeV infection can cause lethal disease in humans and horses, and to date all cases of human HeV disease have resulted from contact with infected horses. Currently, diagnosis of acute HeV infections in horses relies on the productive phase of infection when virus shedding may occur. An assay that identifies infected horses during the preclinical phase of infection would reduce the risk of zoonotic viral transmission during management of HeV outbreaks. Having previously shown that the host microRNA (miR)-146a is upregulated in the blood of HeV-infected horses days prior to the detection of viremia, we have profiled miRNAs at the transcriptome-wide level to comprehensively assess differences between infected and uninfected horses. Next-generation sequencing and the miRDeep2 algorithm identified 742 mature miRNA transcripts corresponding to 593 miRNAs in whole blood of six horses (three HeV-infected, three uninfected). Thirty seven miRNAs were differentially expressed in infected horses, two of which were validated by qRT-PCR. This study describes a methodology for the transcriptome-wide profiling of miRNAs in whole blood and supports the notion that measuring host miRNA expression levels may aid infectious disease diagnosis in the future.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2017-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

Stephen M. Rawlinson / Tianyue Zhao / Ashley M. Rozario / Christina L. Rootes / Paul J. McMillan / Anthony W. Purcell / Amanda Woon / Glenn A. Marsh / Kim G. Lieu / Lin-Fa Wang / Hans J. Netter / Toby D. M. Bell / Cameron R. Stewart / Gregory W. Moseley

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 13

Abstract: Many RNA viruses that replicate in the cytoplasm express proteins that localize to nucleoli, but the nucleolar functions remain largely unknown. Here, the authors show that the Henipavirus matrix protein mimics an endogenous Treacle partner of the DNA- ... ...

Abstract	Many RNA viruses that replicate in the cytoplasm express proteins that localize to nucleoli, but the nucleolar functions remain largely unknown. Here, the authors show that the Henipavirus matrix protein mimics an endogenous Treacle partner of the DNA-damage response, resulting in suppression of rRNA biogenesis.
Keywords	Science ; Q
Language	English
Publishing date	2018-08-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 13

Abstract	Many RNA viruses that replicate in the cytoplasm express proteins that localize to nucleoli, but the nucleolar functions remain largely unknown. Here, the authors show that the Henipavirus matrix protein mimics an endogenous Treacle partner of the DNA-damage response, resulting in suppression of rRNA biogenesis.
Keywords	Science ; Q
Language	English
Publishing date	2018-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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