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Artikel ; Online: SARS-CoV-2 in Domestic UK Cats from Alpha to Omicron: Swab Surveillance and Case Reports.

Jones, Sarah / Tyson, Grace B / Orton, Richard J / Smollett, Katherine / Manna, Federica / Kwok, Kirsty / Suárez, Nicolás M / Logan, Nicola / McDonald, Michael / Bowie, Andrea / Filipe, Ana Da Silva / Willett, Brian J / Weir, William / Hosie, Margaret J

Viruses

2023 Band 15, Heft 8

Abstract: Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive ... ...

Abstract	Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified by active surveillance (1/549, 0.18%), during the Delta wave (1/175, 0.57%). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. These cases demonstrate that, although uncommon in cats, a variety of clinical signs can occur.
Mesh-Begriff(e)	Animals ; Cats ; SARS-CoV-2/genetics ; COVID-19/diagnosis ; COVID-19/veterinary ; Antibodies, Viral ; United Kingdom/epidemiology
Chemische Substanzen	Antibodies, Viral
Sprache	Englisch
Erscheinungsdatum	2023-08-19
Erscheinungsland	Switzerland
Dokumenttyp	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15081769
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning.

Meehan, Gavin R / Herder, Vanessa / Allan, Jay / Huang, Xinyi / Kerr, Karen / Mendonca, Diogo Correa / Ilia, Georgios / Wright, Derek W / Nomikou, Kyriaki / Gu, Quan / Molina Arias, Sergi / Hansmann, Florian / Hardas, Alexandros / Attipa, Charalampos / De Lorenzo, Giuditta / Cowton, Vanessa / Upfold, Nicole / Palmalux, Natasha / Brown, Jonathan C /

Barclay, Wendy S / Filipe, Ana Da Silva / Furnon, Wilhelm / Patel, Arvind H / Palmarini, Massimo

PLoS pathogens

2023 Band 19, Heft 11, Seite(n) e1011589

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to evolve throughout the coronavirus disease-19 (COVID-19) pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to evolve throughout the coronavirus disease-19 (COVID-19) pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.1 (Omicron) was shown to be attenuated compared to the previous VOCs like Delta, but it is possible that newly emerging variants may regain a virulent phenotype. Hamsters have been proven to be an exceedingly good model for SARS-CoV-2 pathogenesis. Here, we aimed to develop robust quantitative pipelines to assess the virulence of SARS-CoV-2 variants in hamsters. We used various approaches including RNAseq, RNA in situ hybridization, immunohistochemistry, and digital pathology, including software assisted whole section imaging and downstream automatic analyses enhanced by machine learning, to develop methods to assess and quantify virus-induced pulmonary lesions in an unbiased manner. Initially, we used Delta and Omicron to develop our experimental pipelines. We then assessed the virulence of recent Omicron sub-lineages including BA.5, XBB, BQ.1.18, BA.2, BA.2.75 and EG.5.1. We show that in experimentally infected hamsters, accurate quantification of alveolar epithelial hyperplasia and macrophage infiltrates represent robust markers for assessing the extent of virus-induced pulmonary pathology, and hence virus virulence. In addition, using these pipelines, we could reveal how some Omicron sub-lineages (e.g., BA.2.75 and EG.5.1) have regained virulence compared to the original BA.1. Finally, to maximise the utility of the digital pathology pipelines reported in our study, we developed an online repository containing representative whole organ histopathology sections that can be visualised at variable magnifications (https://covid-atlas.cvr.gla.ac.uk). Overall, this pipeline can provide unbiased and invaluable data for rapidly assessing newly emerging variants and their potential to cause severe disease.
Mesh-Begriff(e)	Animals ; Cricetinae ; Humans ; SARS-CoV-2/genetics ; COVID-19 ; Virulence ; Machine Learning
Sprache	Englisch
Erscheinungsdatum	2023-11-07
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011589
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Population genomics of louping ill virus provide new insights into the evolution of tick-borne flaviviruses.

Clark, Jordan J / Gilray, Janice / Orton, Richard J / Baird, Margaret / Wilkie, Gavin / Filipe, Ana da Silva / Johnson, Nicholas / McInnes, Colin J / Kohl, Alain / Biek, Roman

PLoS neglected tropical diseases

2020 Band 14, Heft 9, Seite(n) e0008133

Abstract: The emergence and spread of tick-borne arboviruses pose an increased challenge to human and animal health. In Europe this is demonstrated by the increasingly wide distribution of tick-borne encephalitis virus (TBEV, Flavivirus, Flaviviridae), which has ... ...

Abstract	The emergence and spread of tick-borne arboviruses pose an increased challenge to human and animal health. In Europe this is demonstrated by the increasingly wide distribution of tick-borne encephalitis virus (TBEV, Flavivirus, Flaviviridae), which has recently been found in the United Kingdom (UK). However, much less is known about other tick-borne flaviviruses (TBFV), such as the closely related louping ill virus (LIV), an animal pathogen which is endemic to the UK and Ireland, but which has been detected in other parts of Europe including Scandinavia and Russia. The emergence and potential spatial overlap of these viruses necessitates improved understanding of LIV genomic diversity, geographic spread and evolutionary history. We sequenced a virus archive composed of 22 LIV isolates which had been sampled throughout the UK over a period of over 80 years. Combining this dataset with published virus sequences, we detected no sign of recombination and found low diversity and limited evidence for positive selection in the LIV genome. Phylogenetic analysis provided evidence of geographic clustering as well as long-distance movement, including movement events that appear recent. However, despite genomic data and an 80-year time span, we found that the data contained insufficient temporal signal to reliably estimate a molecular clock rate for LIV. Additional analyses revealed that this also applied to TBEV, albeit to a lesser extent, pointing to a general problem with phylogenetic dating for TBFV. The 22 LIV genomes generated during this study provide a more reliable LIV phylogeny, improving our knowledge of the evolution of tick-borne flaviviruses. Our inability to estimate a molecular clock rate for both LIV and TBEV suggests that temporal calibration of tick-borne flavivirus evolution should be interpreted with caution and highlight a unique aspect of these viruses which may be explained by their reliance on tick vectors.
Mesh-Begriff(e)	Animals ; Cell Line ; Cricetinae ; Encephalitis Viruses, Tick-Borne/classification ; Encephalitis Viruses, Tick-Borne/genetics ; Encephalitis, Tick-Borne/virology ; Evolution, Molecular ; Genetics, Population ; Genome, Viral ; Metagenomics ; Phylogeny ; Sequence Analysis, RNA ; Sheep ; United Kingdom
Sprache	Englisch
Erscheinungsdatum	2020-09-14
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0008133
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Epidemiology and biology of a herpesvirus in rabies endemic vampire bat populations.

Griffiths, Megan E / Bergner, Laura M / Broos, Alice / Meza, Diana K / Filipe, Ana da Silva / Davison, Andrew / Tello, Carlos / Becker, Daniel J / Streicker, Daniel G

Nature communications

2020 Band 11, Heft 1, Seite(n) 5951

Abstract: Rabies is a viral zoonosis transmitted by vampire bats across Latin America. Substantial public health and agricultural burdens remain, despite decades of bats culls and livestock vaccinations. Virally vectored vaccines that spread autonomously through ... ...

Abstract	Rabies is a viral zoonosis transmitted by vampire bats across Latin America. Substantial public health and agricultural burdens remain, despite decades of bats culls and livestock vaccinations. Virally vectored vaccines that spread autonomously through bat populations are a theoretically appealing solution to managing rabies in its reservoir host. We investigate the biological and epidemiological suitability of a vampire bat betaherpesvirus (DrBHV) to act as a vaccine vector. In 25 sites across Peru with serological and/or molecular evidence of rabies circulation, DrBHV infects 80-100% of bats, suggesting potential for high population-level vaccine coverage. Phylogenetic analysis reveals host specificity within neotropical bats, limiting risks to non-target species. Finally, deep sequencing illustrates DrBHV super-infections in individual bats, implying that DrBHV-vectored vaccines might invade despite the highly prevalent wild-type virus. These results indicate DrBHV as a promising candidate vector for a transmissible rabies vaccine, and provide a framework to discover and evaluate candidate viral vectors for vaccines against bat-borne zoonoses.
Mesh-Begriff(e)	Animals ; Betaherpesvirinae/classification ; Betaherpesvirinae/genetics ; Betaherpesvirinae/physiology ; Biological Coevolution ; Cattle ; Chiroptera/classification ; Chiroptera/virology ; Genome, Viral/genetics ; Herpesviridae Infections/epidemiology ; Herpesviridae Infections/veterinary ; Herpesviridae Infections/virology ; Host Specificity ; Mammals/classification ; Mammals/virology ; Peru/epidemiology ; Phylogeny ; Rabies/epidemiology ; Rabies/prevention & control ; Rabies/transmission ; Rabies/veterinary ; Rabies virus/immunology ; Rabies virus/physiology ; Seroepidemiologic Studies ; Superinfection/veterinary ; Superinfection/virology
Sprache	Englisch
Erscheinungsdatum	2020-11-23
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-19832-4
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning

bioRxiv

Abstract: SARS-CoV-2 has continued to evolve throughout the COVID-19 pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any ... ...

Abstract	SARS-CoV-2 has continued to evolve throughout the COVID-19 pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.1 (Omicron) was shown to be attenuated compared to the previous VOCs like Delta, but it is possible that newly emerging variants may regain a virulent phenotype. Hamsters have been proven to be an exceedingly good model for SARS-CoV-2 pathogenesis. Here, we aimed to develop robust quantitative pipelines to assess the virulence of SARS-CoV-2 variants in hamsters. We used various approaches including RNAseq, RNA in situ hybridization, immunohistochemistry, and digital pathology, including software assisted whole section imaging and downstream automatic analyses enhanced by machine learning, to develop methods to assess and quantify virus-induced pulmonary lesions in an unbiased manner. Initially, we used Delta and Omicron to develop our experimental pipelines. We then assessed the virulence of recent Omicron sub-lineages including BA.5, XBB, BQ.1.18, BA.2 and BA.2.75. We show that in experimentally infected hamsters, accurate quantification of alveolar epithelial hyperplasia and macrophage infiltrates represent robust markers for assessing the extent of virus-induced pulmonary pathology, and hence virus virulence. In addition, using these pipelines, we could reveal how some Omicron sub-lineages (e.g., BA.2.75) have regained virulence compared to the original BA.1. Finally, to maximise the utility of the digital pathology pipelines reported in our study, we developed an online repository containing representative whole organ histopathology sections that can be visualised at variable magnifications (https://covid-atlas.cvr.gla.ac.uk). Overall, this pipeline can provide unbiased and invaluable data for rapidly assessing newly emerging variants and their potential to cause severe disease.
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2023-08-01
Verlag	Cold Spring Harbor Laboratory
Dokumenttyp	Artikel ; Online
DOI	10.1101/2023.08.01.551417
Datenquelle	COVID19

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Artikel ; Online: A polymorphic residue that attenuates the antiviral potential of interferon lambda 4 in hominid lineages.

Bamford, Connor G G / Aranday-Cortes, Elihu / Filipe, Ines Cordeiro / Sukumar, Swathi / Mair, Daniel / Filipe, Ana da Silva / Mendoza, Juan L / Garcia, K Christopher / Fan, Shaohua / Tishkoff, Sarah A / McLauchlan, John

PLoS pathogens

2018 Band 14, Heft 10, Seite(n) e1007307

Abstract: As antimicrobial signalling molecules, type III or lambda interferons (IFNλs) are critical for defence against infection by diverse pathogens, including bacteria, fungi and viruses. Counter-intuitively, expression of one member of the family, IFNλ4, is ... ...

Abstract	As antimicrobial signalling molecules, type III or lambda interferons (IFNλs) are critical for defence against infection by diverse pathogens, including bacteria, fungi and viruses. Counter-intuitively, expression of one member of the family, IFNλ4, is associated with decreased clearance of hepatitis C virus (HCV) in the human population; by contrast, a natural frameshift mutation that abrogates IFNλ4 production improves HCV clearance. To further understand how genetic variation between and within species affects IFNλ4 function, we screened a panel of all known extant coding variants of human IFNλ4 for their antiviral potential and identify three that substantially affect activity: P70S, L79F and K154E. The most notable variant was K154E, which was found in African Congo rainforest 'Pygmy' hunter-gatherers. K154E greatly enhanced in vitro activity in a range of antiviral (HCV, Zika virus, influenza virus and encephalomyocarditis virus) and gene expression assays. Remarkably, E154 is the ancestral residue in mammalian IFNλ4s and is extremely well conserved, yet K154 has been fixed throughout evolution of the hominid genus Homo, including Neanderthals. Compared to chimpanzee IFNλ4, the human orthologue had reduced activity due to amino acid K154. Comparison of published gene expression data from humans and chimpanzees showed that this difference in activity between K154 and E154 in IFNλ4 correlates with differences in antiviral gene expression in vivo during HCV infection. Mechanistically, our data show that the human-specific K154 negatively affects IFNλ4 activity through a novel means by reducing its secretion and potency. We thus demonstrate that attenuated activity of IFNλ4 is conserved among humans and postulate that differences in IFNλ4 activity between species contribute to distinct host-specific responses to-and outcomes of-infection, such as HCV infection. The driver of reduced IFNλ4 antiviral activity in humans remains unknown but likely arose between 6 million and 360,000 years ago in Africa.
Mesh-Begriff(e)	Animals ; Antiviral Agents/therapeutic use ; Biological Evolution ; Cardiovirus Infections/drug therapy ; Cardiovirus Infections/genetics ; Cardiovirus Infections/virology ; Cells, Cultured ; Encephalomyocarditis virus/drug effects ; Encephalomyocarditis virus/isolation & purification ; Gene Expression Regulation ; Hepacivirus/drug effects ; Hepacivirus/isolation & purification ; Hepatitis C/drug therapy ; Hepatitis C/genetics ; Hepatitis C/virology ; Humans ; Interleukins/genetics ; Pan troglodytes ; Polymorphism, Single Nucleotide ; Species Specificity ; Zika Virus/drug effects ; Zika Virus/isolation & purification ; Zika Virus Infection/drug therapy ; Zika Virus Infection/genetics ; Zika Virus Infection/virology
Chemische Substanzen	Antiviral Agents ; IFNL4 protein, human ; Interleukins
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2018-10-11
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1007307
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Metagenomic next-generation sequencing aids the diagnosis of viral infections in febrile returning travellers.

Jerome, Hanna / Taylor, Callum / Sreenu, Vattipally B / Klymenko, Tanya / Filipe, Ana Da Silva / Jackson, Celia / Davis, Chris / Ashraf, Shirin / Wilson-Davies, Eleri / Jesudason, Natasha / Devine, Karen / Harder, Lisbeth / Aitken, Celia / Gunson, Rory / Thomson, Emma C

The Journal of infection

2019 Band 79, Heft 4, Seite(n) 383–388

Abstract: Objectives: Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a ... ...

Abstract	Objectives: Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a single center to explore its suitability as a diagnostic tool. Methods: Plasma samples from 40 returning travellers presenting with a fever of ≥38°C were sequenced using MNGS on the Illumina MiSeq platform and compared with standard-of-care diagnostic assays. Results: In total, 11/40 patients were diagnosed with a viral infection. Standard of care diagnostics revealed 5 viral infections using plasma samples; dengue virus 1 (n = 2), hepatitis E (n = 1), Ebola virus (n = 1) and hepatitis A (n = 1), all of which were detected by MNGS. Three additional patients with Chikungunya virus (n = 2) and mumps virus were diagnosed by MNGS only. Respiratory infections detected by nasal/throat swabs only were not detected by MNGS of plasma. One patient had infection with malaria and mumps virus during the same admission. Conclusions: MNGS analysis of plasma samples improves the sensitivity of diagnosis of viral infections and has potential as an all-in-one diagnostic test. It can be used to identify infections that have not been considered by the treating physician, co-infections and new or emerging pathogens. Summary: Next generation sequencing (NGS) has potential as an all-in-one diagnostic test. In this study we used NGS to diagnose returning travellers with acute febrile illness in the UK, highlighting cases where the diagnosis was missed using standard methods.
Mesh-Begriff(e)	Adult ; Bacterial Infections/diagnosis ; Bacterial Infections/microbiology ; Fever/virology ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics ; Parasitic Diseases/diagnosis ; Parasitic Diseases/parasitology ; Proof of Concept Study ; RNA, Viral/genetics ; Respiratory Tract Infections/blood ; Respiratory Tract Infections/diagnosis ; Respiratory Tract Infections/microbiology ; Respiratory Tract Infections/virology ; Retrospective Studies ; Sensitivity and Specificity ; Travel/statistics & numerical data ; Travel-Related Illness ; Virus Diseases/blood ; Virus Diseases/diagnosis ; Viruses/genetics ; Viruses/pathogenicity
Chemische Substanzen	RNA, Viral
Sprache	Englisch
Erscheinungsdatum	2019-08-06
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424417-5
ISSN	1532-2742 ; 0163-4453
ISSN (online)	1532-2742
ISSN	0163-4453
DOI	10.1016/j.jinf.2019.08.003
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: "Frozen evolution" of an RNA virus suggests accidental release as a potential cause of arbovirus re-emergence.

PLoS biology

2020 Band 18, Heft 4, Seite(n) e3000673

Abstract: The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an arthropod-borne virus of ruminants, emerged in livestock in northern Europe in 2006, ... ...

Abstract	The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an arthropod-borne virus of ruminants, emerged in livestock in northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of euros. Although the outbreak was successfully controlled through vaccination by early 2010, puzzlingly, a closely related BTV-8 strain re-emerged in France in 2015, triggering a second outbreak that is still ongoing. The origin of this virus and the mechanisms underlying its re-emergence are unknown. Here, we performed phylogenetic analyses of 164 whole BTV-8 genomes sampled throughout the two outbreaks. We demonstrate consistent clock-like virus evolution during both epizootics but found negligible evolutionary change between them. We estimate that the ancestor of the second outbreak dates from the height of the first outbreak in 2008. This implies that the virus had not been replicating for multiple years prior to its re-emergence in 2015. Given the absence of any known natural mechanism that could explain BTV-8 persistence over this long period without replication, we hypothesise that the second outbreak could have been initiated by accidental exposure of livestock to frozen material contaminated with virus from approximately 2008. Our work highlights new targets for pathogen surveillance programmes in livestock and illustrates the power of genomic epidemiology to identify pathways of infectious disease emergence.
Mesh-Begriff(e)	Animals ; Biological Evolution ; Bluetongue/epidemiology ; Bluetongue/virology ; Bluetongue virus/genetics ; Bluetongue virus/physiology ; Disease Outbreaks ; Europe/epidemiology ; France ; Genome, Viral ; Livestock/virology ; Mutation ; Phylogeny
Sprache	Englisch
Erscheinungsdatum	2020-04-28
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3000673
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Subgenomic RNA identification in SARS-CoV-2 genomic sequencing data.

Parker, Matthew D / Lindsey, Benjamin B / Leary, Shay / Gaudieri, Silvana / Chopra, Abha / Wyles, Matthew / Angyal, Adrienn / Green, Luke R / Parsons, Paul / Tucker, Rachel M / Brown, Rebecca / Groves, Danielle / Johnson, Katie / Carrilero, Laura / Heffer, Joe / Partridge, David G / Evans, Cariad / Raza, Mohammad / Keeley, Alexander J /

Smith, Nikki / Filipe, Ana Da Silva / Shepherd, James G / Davis, Chris / Bennett, Sahan / Sreenu, Vattipally B / Kohl, Alain / Aranday-Cortes, Elihu / Tong, Lily / Nichols, Jenna / Thomson, Emma C / Wang, Dennis / Mallal, Simon / de Silva, Thushan I

Genome research

2021 Band 31, Heft 4, Seite(n) 645–658

Abstract: We have developed periscope, a tool for the detection and quantification of subgenomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed " ... ...

Abstract	We have developed periscope, a tool for the detection and quantification of subgenomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation of the SARS-CoV-2 RNA genome for most open reading frames (ORFs) occurs via RNA intermediates termed "subgenomic RNAs." sgRNAs are produced through discontinuous transcription, which relies on homology between transcription regulatory sequences (TRS-B) upstream of the ORF start codons and that of the TRS-L, which is located in the 5' UTR. TRS-L is immediately preceded by a leader sequence. This leader sequence is therefore found at the 5' end of all sgRNA. We applied periscope to 1155 SARS-CoV-2 genomes from Sheffield, United Kingdom, and validated our findings using orthogonal data sets and in vitro cell systems. By using a simple local alignment to detect reads that contain the leader sequence, we were able to identify and quantify reads arising from canonical and noncanonical sgRNA. We were able to detect all canonical sgRNAs at the expected abundances, with the exception of ORF10. A number of recurrent noncanonical sgRNAs are detected. We show that the results are reproducible using technical replicates and determine the optimum number of reads for sgRNA analysis. In VeroE6
Mesh-Begriff(e)	Animals ; Base Sequence ; Chlorocebus aethiops ; Genome, Viral ; Humans ; Limit of Detection ; RNA, Viral/genetics ; SARS-CoV-2/genetics ; Sequence Analysis, RNA/methods ; Vero Cells
Chemische Substanzen	RNA, Viral
Sprache	Englisch
Erscheinungsdatum	2021-03-15
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.268110.120
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Viral genotype correlates with distinct liver gene transcription signatures in chronic hepatitis C virus infection.

Robinson, Mark W / Aranday-Cortes, Elihu / Gatherer, Derek / Swann, Rachael / Liefhebber, Jolanda M P / Filipe, Ana Da Silva / Sigruener, Alex / Barclay, Stephen T / Mills, Peter R / Patel, Arvind H / McLauchlan, John

Liver international : official journal of the International Association for the Study of the Liver

2015 Band 35, Heft 10, Seite(n) 2256–2264

Abstract: Background: Chronic hepatitis C virus (HCV) infection of the liver with either genotype 1 or genotype 3 gives rise to distinct pathologies, and the two viral genotypes respond differently to antiviral therapy.: Methods: To understand these clinical ... ...

Abstract	Background: Chronic hepatitis C virus (HCV) infection of the liver with either genotype 1 or genotype 3 gives rise to distinct pathologies, and the two viral genotypes respond differently to antiviral therapy. Methods: To understand these clinical differences, we compared gene transcription profiles in liver biopsies from patients infected with either gt1 or gt3, and uninfected controls. Results: Gt1-infected biopsies displayed elevated levels of transcripts regulated by type I and type III interferons (IFN), including genes that predict response to IFN-α therapy. In contrast, genes controlled by IFN-γ were induced in gt3-infected biopsies. Moreover, IFN-γ levels were higher in gt3-infected biopsies. Analysis of hepatocyte-derived cell lines confirmed that the genes upregulated in gt3 infection were preferentially induced by IFN-γ. The transcriptional profile of gt3 infection was unaffected by IFNL4 polymorphisms, providing a rationale for the reduced predictive power of IFNL genotyping in gt3-infected patients. Conclusions: The interactions between HCV genotypes 1 and 3 and hepatocytes are distinct. These unique interactions provide avenues to explore the biological mechanisms that drive viral genotype-specific differences in disease progression and treatment response. A greater understanding of the distinct host-pathogen interactions of the different HCV genotypes is required to facilitate optimal management of HCV infection.
Mesh-Begriff(e)	Adult ; Cell Line ; Female ; Genotype ; Hepatitis C/genetics ; Hepatitis C, Chronic/genetics ; Host-Pathogen Interactions ; Humans ; Interferon-gamma/metabolism ; Interleukins/genetics ; Liver/pathology ; Male ; Middle Aged ; Polymorphism, Genetic ; Transcription, Genetic ; Transcriptome
Chemische Substanzen	IFNG protein, human ; IFNL4 protein, human ; Interleukins ; Interferon-gamma (82115-62-6)
Sprache	Englisch
Erscheinungsdatum	2015-04-07
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2102783-3
ISSN	1478-3231 ; 1478-3223
ISSN (online)	1478-3231
ISSN	1478-3223
DOI	10.1111/liv.12830
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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