Publications by authors named "Edward C Holmes"

552 Publications

Emergence and Spread of SARS-CoV-2 Lineages B.1.1.7 and P.1 in Italy.

Viruses 2021 04 29;13(5). Epub 2021 Apr 29.

Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise G. Caporale, 641000 Teramo, Italy.

Italy's second wave of SARS-CoV-2 has hit hard, with more than three million cases and over 100,000 deaths, representing an almost ten-fold increase in the numbers reported by August 2020. Herein, we present an analysis of 6515 SARS-CoV-2 sequences sampled in Italy between 29 January 2020 and 1 March 2021 and show how different lineages emerged multiple times independently despite lockdown restrictions. Virus lineage B.1.177 became the dominant variant in November 2020, when cases peaked at 40,000 a day, but since January 2021 this is being replaced by the B.1.1.7 'variant of concern'. In addition, we report a sudden increase in another documented variant of concern-lineage P.1-from December 2020 onwards, most likely caused by a single introduction into Italy. We again highlight how international importations drive the emergence of new lineages and that genome sequencing should remain a top priority for ongoing surveillance in Italy.
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http://dx.doi.org/10.3390/v13050794DOI Listing
April 2021

Use of Genomics to Track Coronavirus Disease Outbreaks, New Zealand.

Emerg Infect Dis 2021 05;27(5):1317-1322

Real-time genomic sequencing has played a major role in tracking the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), contributing greatly to disease mitigation strategies. In August 2020, after having eliminated the virus, New Zealand experienced a second outbreak. During that outbreak, New Zealand used genomic sequencing in a primary role, leading to a second elimination of the virus. We generated genomes from 78% of the laboratory-confirmed samples of SARS-CoV-2 from the second outbreak and compared them with the available global genomic data. Genomic sequencing rapidly identified that virus causing the second outbreak in New Zealand belonged to a single cluster, thus resulting from a single introduction. However, successful identification of the origin of this outbreak was impeded by substantial biases and gaps in global sequencing data. Access to a broader and more heterogenous sample of global genomic data would strengthen efforts to locate the source of any new outbreaks.
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http://dx.doi.org/10.3201/eid2705.204579DOI Listing
May 2021

How accurately can we assess zoonotic risk?

PLoS Biol 2021 Apr 20;19(4):e3001135. Epub 2021 Apr 20.

Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, Australia.

Identifying the animal reservoirs from which zoonotic viruses will likely emerge is central to understanding the determinants of disease emergence. Accordingly, there has been an increase in studies attempting zoonotic "risk assessment." Herein, we demonstrate that the virological data on which these analyses are conducted are incomplete, biased, and rapidly changing with ongoing virus discovery. Together, these shortcomings suggest that attempts to assess zoonotic risk using available virological data are likely to be inaccurate and largely only identify those host taxa that have been studied most extensively. We suggest that virus surveillance at the human-animal interface may be more productive.
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http://dx.doi.org/10.1371/journal.pbio.3001135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057571PMC
April 2021

Field and classroom initiatives for portable sequence-based monitoring of dengue virus in Brazil.

Nat Commun 2021 04 16;12(1):2296. Epub 2021 Apr 16.

Fundação Oswaldo Cruz, Bio-Manguinhos, Rio de Janeiro, Rio de Janeiro, Brazil.

Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015-2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses.
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http://dx.doi.org/10.1038/s41467-021-22607-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052316PMC
April 2021

Pathogenicity and transmissibility of a novel respirovirus isolated from a Malayan pangolin.

J Gen Virol 2021 04;102(4)

Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China.

The identification of SARS-CoV-2-like viruses in Malayan pangolins () has focused attention on these endangered animals and the viruses they carry. We successfully isolated a novel respirovirus from the lungs of a dead Malayan pangolin. Similar to murine respirovirus, the full-length genome of this novel virus was 15 384 nucleotides comprising six genes in the order 3'-(leader)-NP-P-M-F-HN-l-(trailer)-5'. Phylogenetic analysis revealed that this virus belongs to the genus and is most closely related to murine respirovirus. Notably, animal infection experiments indicated that the pangolin virus is highly pathogenic and transmissible in mice, with inoculated mice having variable clinical symptoms and a fatality rate of 70.37 %. The virus was found to replicate in most tissues with the exception of muscle and heart. Contact transmission of the virus was 100 % efficient, although the mice in the contact group displayed milder symptoms, with the virus mainly being detected in the trachea and lungs. The isolation of a novel respirovirus from the Malayan pangolin provides new insight into the evolution and distribution of this important group of viruses and again demonstrates the potential infectious disease threats faced by endangered pangolins.
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http://dx.doi.org/10.1099/jgv.0.001586DOI Listing
April 2021

A Novel Rubi-Like Virus in the Pacific Electric Ray () Reveals the Complex Evolutionary History of the .

Viruses 2021 03 31;13(4). Epub 2021 Mar 31.

Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand.

(RuV) is the causative agent of rubella ("German measles") and remains a global health concern. Until recently, RuV was the only known member of the genus and the only virus species classified within the family of positive-sense RNA viruses. Recently, two new rubella-like matonaviruses, and , have been identified in several mammalian species, along with more divergent viruses in fish and reptiles. To screen for the presence of additional novel rubella-like viruses, we mined published transcriptome data using genome sequences from , , and as baits. From this, we identified a novel rubella-like virus in a transcriptome of -order Torpediniformes (Pacific electric ray)-that is more closely related to mammalian than to the divergent fish matonavirus and indicative of a complex pattern of cross-species virus transmission. Analysis of host reads confirmed that the sample analysed was indeed from a Pacific electric ray, and two other viruses identified in this animal, from the and , grouped with other fish viruses. These findings indicate that the evolutionary history of the is more complex than previously thought and highlights the vast number of viruses that remain undiscovered.
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http://dx.doi.org/10.3390/v13040585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067182PMC
March 2021

Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes.

Science 2021 04 9;372(6540):363-370. Epub 2021 Mar 9.

Department of Bioengineering, McGill University, Montreal, QC H3A 0C3, Canada.

Given vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two critical issues arise: How timing of delivery of the second dose will affect infection dynamics and how it will affect prospects for the evolution of viral immune escape via a buildup of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose as compared with natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short term, focusing on one dose generally decreases infections, but that longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose and to ramp up vaccination efforts globally.
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http://dx.doi.org/10.1126/science.abg8663DOI Listing
April 2021

Virome composition in marine fish revealed by meta-transcriptomics.

Virus Evol 2021 Jan 4;7(1):veab005. Epub 2021 Feb 4.

Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia.

Revealing the determinants of virome composition is central to placing disease emergence in a broader evolutionary context. Fish are the most species-rich group of vertebrates and so provide an ideal model system to study the factors that shape virome compositions and their evolution. We characterized the viromes of nineteen wild-caught species of marine fish using total RNA sequencing (meta-transcriptomics) combined with analyses of sequence and protein structural homology to identify divergent viruses that often evade characterization. From this, we identified twenty-five new vertebrate-associated viruses and a further twenty-two viruses likely associated with fish diet or their microbiomes. The vertebrate-associated viruses identified here included the first fish virus in the (single-strand, negative-sense RNA virus) Other viruses fell within the , , , , , , , , , and , and were sometimes phylogenetically distinct from known fish viruses. We also show how key metrics of virome composition-viral richness, abundance, and diversity-can be analysed along with host ecological and biological factors as a means to understand virus ecology. Accordingly, these data suggest that that the vertebrate-associated viromes of the fish sampled here are predominantly shaped by the phylogenetic history (i.e. taxonomic order) of their hosts, along with several biological factors including water temperature, habitat depth, community diversity and swimming behaviour. No such correlations were found for viruses associated with porifera, molluscs, arthropods, fungi, and algae, that are unlikely to replicate in fish hosts. Overall, these data indicate that fish harbour particularly large and complex viromes and the vast majority of fish viromes are undescribed.
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http://dx.doi.org/10.1093/ve/veab005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887440PMC
January 2021

Understanding the Impact of Resistance to Influenza Antivirals.

Clin Microbiol Rev 2021 Mar 10;34(2). Epub 2021 Feb 10.

Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.

SUMMARYInfluenza poses a significant burden on society and health care systems. Although antivirals are an integral tool in effective influenza management, the potential for the emergence of antiviral-resistant viruses can lead to uncertainty and hesitation among front-line prescribers and policy makers. Here, we provide an overview of influenza antiviral resistance in context, exploring the key concepts underlying its development and clinical impact. Due to the acute nature of influenza in immunocompetent patients, resistant viruses that develop during antiviral treatment of a single patient ("treatment-emergent resistance") are usually cleared in a relatively short time, with no impact on future antiviral efficacy. In addition, although available data are limited by small numbers of patients, they show that antiviral treatment still provides clinical benefit to the patient within whom resistance emerges. In contrast, the sustained community transmission of resistant variants in the absence of treatment ("acquired resistance") is of greater concern and can potentially render front-line antivirals ineffective. Importantly, however, resistant viruses are usually associated with reduced fitness such that their widespread transmission is relatively rare. Influenza antivirals are an essential part of effective influenza management due to their ability to reduce the risk of complications and death in infected patients. Although antiviral resistance should be taken seriously and requires continuous careful monitoring, it is not comparable to antibiotic resistance in bacteria, which can become permanent and widespread, with far-reaching medical consequences. The benefits of antiviral treatment far outweigh concerns of potential resistance, which in the vast majority of cases does not have a significant clinical impact.
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http://dx.doi.org/10.1128/CMR.00224-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950363PMC
March 2021

Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes.

medRxiv 2021 Feb 3. Epub 2021 Feb 3.

Department of Bioengineering, McGill University, Montreal QC H3A 0C3, Canada.

As the threat of Covid-19 continues and in the face of vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels. How timing of delivery of the second dose affects infection burden but also prospects for the evolution of viral immune escape are critical questions. Both hinge on the strength and duration (i.e. robustness) of the immune response elicited by a single dose, compared to natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short-term, focusing on one dose generally decreases infections, but longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection, evaluating how different second dose delays might drive immune escape via a build-up of partially immune individuals. Under certain scenarios, we find that a one-dose policy may increase the potential for antigenic evolution. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose, and to ramp up vaccination efforts throughout the world.
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http://dx.doi.org/10.1101/2021.02.01.21250944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872380PMC
February 2021

Retrospective meta-transcriptomic identification of severe dengue in a traveller returning from Africa to Sweden, 1990.

One Health 2021 Jun 22;12:100217. Epub 2021 Jan 22.

Public Health Agency of Sweden, Nobels väg 18, SE-171 82 Solna, Sweden.

Pathogens associated with haemorrhagic fever commonly have zoonotic origins. The first documented imported case of likely viral severe haemorrhagic fever in Sweden occurred in 1990. Despite extensive study, no aetiological agent was identified. Following retrospective investigation with total RNA-sequencing of samples collected between 7 and 36 days from onset of symptoms we identified dengue virus 3 (DENV-3) and a human pegivirus (HPgV). We conclude that the patient likely suffered from haemorrhagic symptoms due to an atypical severe and undiagnosed dengue infection.
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http://dx.doi.org/10.1016/j.onehlt.2021.100217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851179PMC
June 2021

Addendum: A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology.

Nat Microbiol 2021 03;6(3):415

Department of Zoology, University of Oxford, Oxford, UK.

An Addendum to this paper has been published: https://doi.org/10.1038/s41564-021-00872-5.
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http://dx.doi.org/10.1038/s41564-021-00872-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845574PMC
March 2021

Bioinformatics resources for SARS-CoV-2 discovery and surveillance.

Brief Bioinform 2021 03;22(2):631-641

Shandong First Medical University, China.

In early January 2020, the novel coronavirus (SARS-CoV-2) responsible for a pneumonia outbreak in Wuhan, China, was identified using next-generation sequencing (NGS) and readily available bioinformatics pipelines. In addition to virus discovery, these NGS technologies and bioinformatics resources are currently being employed for ongoing genomic surveillance of SARS-CoV-2 worldwide, tracking its spread, evolution and patterns of variation on a global scale. In this review, we summarize the bioinformatics resources used for the discovery and surveillance of SARS-CoV-2. We also discuss the advantages and disadvantages of these bioinformatics resources and highlight areas where additional technical developments are urgently needed. Solutions to these problems will be beneficial not only to the prevention and control of the current COVID-19 pandemic but also to infectious disease outbreaks of the future.
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http://dx.doi.org/10.1093/bib/bbaa386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929396PMC
March 2021

Genomic Evidence of In-Flight Transmission of SARS-CoV-2 Despite Predeparture Testing.

Emerg Infect Dis 2021 03 5;27(3):687-693. Epub 2021 Jan 5.

Since the first wave of coronavirus disease in March 2020, citizens and permanent residents returning to New Zealand have been required to undergo managed isolation and quarantine (MIQ) for 14 days and mandatory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of October 20, 2020, of 62,698 arrivals, testing of persons in MIQ had identified 215 cases of SARS-CoV-2 infection. Among 86 passengers on a flight from Dubai, United Arab Emirates, that arrived in New Zealand on September 29, test results were positive for 7 persons in MIQ. These passengers originated from 5 different countries before a layover in Dubai; 5 had negative predeparture SARS-CoV-2 test results. To assess possible points of infection, we analyzed information about their journeys, disease progression, and virus genomic data. All 7 SARS-CoV-2 genomes were genetically identical, except for a single mutation in 1 sample. Despite predeparture testing, multiple instances of in-flight SARS-CoV-2 transmission are likely.
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http://dx.doi.org/10.3201/eid2703.204714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920679PMC
March 2021

Red fox viromes in urban and rural landscapes.

Virus Evol 2020 Jul 25;6(2):veaa065. Epub 2020 Aug 25.

Department of Biological Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.

The Red fox () has established large populations in Australia's urban and rural areas since its introduction following European settlement. The cryptic and highly adaptable nature of foxes allows them to invade cities and live among humans whilst remaining largely unnoticed. Urban living and access to anthropogenic food resources also influence fox ecology. Urban foxes grow larger, live at higher densities, and are more social than their rural counterparts. These ecological changes in urban red foxes are likely to impact the pathogens that they harbour, and foxes could pose a disease risk to humans and other species that share these urban spaces. To investigate this possibility, we used a meta-transcriptomic approach to characterise the virome of urban and rural foxes across the Greater Sydney region in Australia. Urban and rural foxes differed significantly in virome composition, with rural foxes harbouring a greater abundance of viruses compared to their urban counterparts. We identified ten potentially novel vertebrate-associated viruses in both urban and rural foxes, some of which are related to viruses associated with disease in domestic species and humans. These included members of the , , , and as well as rabbit haemorrhagic disease virus-2. This study sheds light on the viruses carried by urban and rural foxes and emphasises the need for greater genomic surveillance of foxes and other invasive species at the human-wildlife interface.
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http://dx.doi.org/10.1093/ve/veaa065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744383PMC
July 2020

Genomic Epidemiology of the First Wave of SARS-CoV-2 in Italy.

Viruses 2020 12 14;12(12). Epub 2020 Dec 14.

Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise G. Caporale, 641000 Teramo, Italy.

Italy was one of the first countries to experience a major epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with >1000 cases confirmed by 1 March 2020. However, virus genome sequence data is sparse and there has been only limited investigation of virus transmission across the country. Here, we provide the most extensive study to date of the genomic epidemiology of SARS-CoV-2 in Italy covering the first wave of infection. We generated 191 new full-length genomes, largely sampled from central Italy (Abruzzo), before, during, and after the enforcement of a nationwide "lockdown" (8 March-3 June). These were combined with 460 published SARS-CoV-2 sequences sampled across Italy. Phylogenetic analysis including global sequence data revealed multiple independent introductions into Italy, with at least 124 instances of sequence clusters representing longer chains of transmission. Eighteen of these transmission clusters emerged before the nation-wide lockdown was implemented on 8 March, and an additional 18 had evidence for transmission between different Italian regions. Extended transmission periods between infections of up to 104 days were observed in five clusters. In addition, we found seven clusters that persisted throughout the lockdown period. Overall, we show how importations were an important driver of the first wave of SARS-CoV-2 in Italy.
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http://dx.doi.org/10.3390/v12121438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765063PMC
December 2020

Collecting and managing taxonomic data with NCBI-taxonomist.

Bioinformatics 2020 Dec 16. Epub 2020 Dec 16.

Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, Australia.

Summary: We present NCBI-taxonomist - a command-line tool written in Python that collects and manages taxonomic data from the National Center for Biotechnology Information (NCBI). NCBI-taxonomist does not depend on a pre-downloaded taxonomic database but can store data locally. NCBI-taxonomist has six commands to map, collect, extract, resolve, import and group taxonomic data that can be linked together to create powerful analytical pipelines. Because many life science databases use the same taxonomic information, the data managed by NCBI-taxonomist is not limited to NCBI and can be used to find data linked to taxonomic information present in other scientific databases.

Availability And Implementation: NCBI-taxonomist is implemented in Python 3 (≥3.8) and available at https://gitlab.com/janpb/ncbi-taxonomist and via PyPi (https://pypi.org/project/ncbi-taxonomist/), as a Docker container (https://gitlab.com/janpb/ncbi-taxonomist/container_registry/) and Singularity (v3.5.3) image (https://cloud.sylabs.io/library/jpb/ncbi-taxonomist). NCBI-taxonomist is licensed under the GPLv3.

Supplementary Information: https://ncbi-taxonomist.readthedocs.io/en/latest/.
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http://dx.doi.org/10.1093/bioinformatics/btaa1027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016462PMC
December 2020

Extensive genetic diversity and host range of rodent-borne coronaviruses.

Virus Evol 2020 Jul 21;6(2):veaa078. Epub 2020 Nov 21.

Shanghai Public Health Clinical Center & School of Life Science, Fudan University, Shanghai 201052, China.

To better understand the genetic diversity, host associations and evolution of coronaviruses (CoVs) in China we analyzed a total of 696 rodents encompassing 16 different species sampled from Zhejiang and Yunnan provinces. Based on reverse transcriptase PCR-based CoV screening of fecal samples and subsequent sequence analysis of the RNA-dependent RNA polymerase gene, we identified CoVs in diverse rodent species, comprising , , , , , , , , and . CoVs were particularly commonplace in , with a detection rate of 12.44 per cent (24/193). Genetic and phylogenetic analysis revealed the presence of three groups of CoVs carried by a range of rodents that were closely related to the Lucheng Rn rat CoV (LRNV), China Rattus CoV HKU24 (ChRCoV_HKU24), and Longquan Rl rat CoV (LRLV) identified previously. One newly identified -associated virus closely related to LRNV lacked an NS2 gene. This virus had a similar genetic organization to AcCoV-JC34, recently discovered in the same rodent species in Yunnan, suggesting that it represents a new viral subtype. Notably, additional variants of LRNV were identified that contained putative non-structural (NS)2b genes located downstream of the NS2 gene that were likely derived from the host genome. Recombination events were also identified in the open reading frame (ORF) 1a gene of Lijiang-71. In sum, these data reveal the substantial genetic diversity and genomic complexity of rodent-borne CoVs, and extend our knowledge of these major wildlife virus reservoirs.
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http://dx.doi.org/10.1093/ve/veaa078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665783PMC
July 2020

A household case evidences shorter shedding of SARS-CoV-2 in naturally infected cats compared to their human owners.

Emerg Microbes Infect 2021 Dec;10(1):376-383

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in domestic and wild cats. However, little is known about natural viral infections of domestic cats, although their importance for modelling disease spread, informing strategies for managing positive human-animal relationships and disease prevention. Here, we describe the SARS-CoV-2 infection in a household of two human adults and sibling cats (one male and two females) using real-time RT-PCR, an ELISA test, viral sequencing, and virus isolation. On May 5th, 2020, the cat-owners tested positive for SARS-CoV-2. Two days later, the male cat showed mild respiratory symptoms and tested positive. Four days after the male cat, the two female cats became positive, asymptomatically. Also, one human and one cat showed antibodies against SARS-CoV-2. All cats excreted detectable SARS-CoV-2 RNA for a shorter duration than humans and viral sequences analysis confirmed human-to-cat transmission. We could not determine if cat-to-cat transmission also occurred.
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http://dx.doi.org/10.1080/22221751.2020.1863132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939552PMC
December 2021

Genomic epidemiology reveals transmission patterns and dynamics of SARS-CoV-2 in Aotearoa New Zealand.

Nat Commun 2020 12 11;11(1):6351. Epub 2020 Dec 11.

Institute of Environmental Science and Research, Wellington, New Zealand.

New Zealand, a geographically remote Pacific island with easily sealable borders, implemented a nationwide 'lockdown' of all non-essential services to curb the spread of COVID-19. Here, we generate 649 SARS-CoV-2 genome sequences from infected patients in New Zealand with samples collected during the 'first wave', representing 56% of all confirmed cases in this time period. Despite its remoteness, the viruses imported into New Zealand represented nearly all of the genomic diversity sequenced from the global virus population. These data helped to quantify the effectiveness of public health interventions. For example, the effective reproductive number, R of New Zealand's largest cluster decreased from 7 to 0.2 within the first week of lockdown. Similarly, only 19% of virus introductions into New Zealand resulted in ongoing transmission of more than one additional case. Overall, these results demonstrate the utility of genomic pathogen surveillance to inform public health and disease mitigation.
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http://dx.doi.org/10.1038/s41467-020-20235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733492PMC
December 2020

Total infectomes of 162 SARS-CoV-2 cases using meta-transcriptomic sequencing.

J Infect 2021 Jan 8;82(1):e44-e48. Epub 2020 Dec 8.

Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China; The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan 250014, China; School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian 271000, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722261PMC
January 2021

SARS-CoV-2 replicates in respiratory ex vivo organ cultures of domestic ruminant species.

Vet Microbiol 2021 Jan 24;252:108933. Epub 2020 Nov 24.

Istituto Zooprofilattico Sperimentale dell' Abruzzo e Molise, Teramo, Italy. Electronic address:

There is strong evidence that severe acute respiratory syndrome 2 virus (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, originated from an animal reservoir. However, the exact mechanisms of emergence, the host species involved, and the risk to domestic and agricultural animals are largely unknown. Some domestic animal species, including cats, ferrets, and minks, have been demonstrated to be susceptible to SARS-CoV-2 infection, while others, such as pigs and chickens, are not. Importantly, the susceptibility of ruminants to SARS-CoV-2 is unknown, even though they often live in close proximity to humans. We investigated the replication and tissue tropism of two different SARS-CoV-2 isolates in the respiratory tract of three farm animal species - cattle, sheep, and pigs - using respiratory ex vivo organ cultures (EVOCs). We demonstrate that the respiratory tissues of cattle and sheep, but not of pigs, sustain viral replication in vitro of both isolates and that SARS-CoV-2 is associated to ACE2-expressing cells of the respiratory tract of both ruminant species. Intriguingly, a SARS-CoV-2 isolate containing an amino acid substitution at site 614 of the spike protein (mutation D614G) replicated at higher magnitude in ex vivo tissues of both ruminant species, supporting previous results obtained using human cells. These results suggest that additional in vivo experiments involving several ruminant species are warranted to determine their potential role in the epidemiology of this virus.
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http://dx.doi.org/10.1016/j.vetmic.2020.108933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685048PMC
January 2021

Response to Brinkmann et al. "Re-assembly of 19th century smallpox vaccine genomes reveals the contemporaneous use of horsepox and horsepox-related viruses in the United States".

Genome Biol 2020 12 4;21(1):287. Epub 2020 Dec 4.

McMaster Ancient DNA Centre, Department of Anthropology, McMaster University, Hamilton, L8S 4L9, Canada.

We thank Brinkmann and colleagues for their correspondence and their further investigation into these American Civil War Era vaccination strains. Here, we summarize the difficulties and caveats of work with ancient DNA.
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http://dx.doi.org/10.1186/s13059-020-02203-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716422PMC
December 2020

Novel hepaci- and pegi-like viruses in native Australian wildlife and non-human primates.

Virus Evol 2020 Jul 20;6(2):veaa064. Epub 2020 Aug 20.

School of Life and Environmental Sciences and School of Medical Sciences, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney 2006, Australia.

The family of positive-sense RNA viruses contains important pathogens of humans and other animals, including Zika virus, dengue virus, and hepatitis C virus. The are currently divided into four genera-, , , and -each with a diverse host range. Members of the genus are associated with an array of animal species, including humans, non-human primates, other mammalian species, as well as birds and fish, while the closely related pegiviruses have been identified in a variety of mammalian taxa, also including humans. Using a combination of total RNA and whole-genome sequencing we identified four novel hepaci-like viruses and one novel variant of a known hepacivirus in five species of Australian wildlife. The hosts infected comprised native Australian marsupials and birds, as well as a native gecko (). From these data we identified a distinct marsupial clade of hepaci-like viruses that also included an engorged tick collected while feeding on Australian long-nosed bandicoots (). Distinct lineages of hepaci-like viruses associated with geckos and birds were also identified. By mining the SRA database we similarly identified three new hepaci-like viruses from avian and primate hosts, as well as two novel pegi-like viruses associated with primates. The phylogenetic history of the hepaci- and pegi-like viruses as a whole, combined with co-phylogenetic analysis, provided support for virus-host co-divergence over the course of vertebrate evolution, although with frequent cross-species virus transmission. Overall, our work highlights the diversity of the and genera as well as the uncertain phylogenetic distinction between.
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http://dx.doi.org/10.1093/ve/veaa064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673076PMC
July 2020

Identification of Novel Astroviruses in the Gastrointestinal Tract of Domestic Cats.

Viruses 2020 11 12;12(11). Epub 2020 Nov 12.

School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, NSW 2006, Australia.

Astroviruses, isolated from numerous avian and mammalian species including humans, are commonly associated with enteritis and encephalitis. Two astroviruses have previously been identified in cats, and while definitive evidence is lacking, an association with enteritis is suggested. Using metagenomic next-generation sequencing of viral nucleic acids from faecal samples, we identified two novel feline astroviruses termed Feline astrovirus 3 and 4. These viruses were isolated from healthy shelter-housed kittens (Feline astrovirus 3; 6448 bp) and from a kitten with diarrhoea that was co-infected with Feline parvovirus (Feline astrovirus 4, 6549 bp). Both novel astroviruses shared a genome arrangement of three open reading frames (ORFs) comparable to that of other astroviruses. Phylogenetic analysis of the concatenated ORFs, ORF1a, ORF1b and capsid protein revealed that both viruses were phylogenetically distinct from other feline astroviruses, although their precise evolutionary history could not be accurately determined due to a lack of resolution at key nodes. Large-scale molecular surveillance studies of healthy and diseased cats are needed to determine the pathogenicity of feline astroviruses as single virus infections or in co-infections with other enteric viruses.
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http://dx.doi.org/10.3390/v12111301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697530PMC
November 2020

Meta-Transcriptomic Identification of Divergent in Fish.

Viruses 2020 11 4;12(11). Epub 2020 Nov 4.

Department of Microbiology and Immunology, University of Otago, Dunedin 9016, New Zealand.

Tilapia lake virus (TiLV) has caused mass mortalities in farmed and wild tilapia with serious economic and ecological consequences. Until recently, this virus was the sole member of the , a family within the order comprising segmented negative-sense RNA viruses. We sought to identify additional viruses within the through total RNA sequencing (meta-transcriptomics) and data mining of published transcriptomes. Accordingly, we sampled marine fish species from both Australia and China and discovered several segments of two new viruses within the , tentatively called and , respectively. In addition, by mining vertebrate transcriptome data, we identified nine additional virus transcripts matching to multiple genomic segments of TiLV in both marine and freshwater fish. These new viruses retained sequence conservation with the distantly related in the RdRp subunit PB1, but formed a distinct and diverse phylogenetic group. These data suggest that the have a broad host range within fish and that greater animal sampling will identify additional divergent members of the .
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http://dx.doi.org/10.3390/v12111254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694244PMC
November 2020

Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage.

EMBO J 2020 12 14;39(24):e105896. Epub 2020 Dec 14.

Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China.

COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.
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http://dx.doi.org/10.15252/embj.2020105896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737620PMC
December 2020

Diverse and abundant resistome in terrestrial and aquatic vertebrates revealed by transcriptional analysis.

Sci Rep 2020 11 2;10(1):18870. Epub 2020 Nov 2.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Despite increasing evidence that antibiotic resistant pathogens are shared among humans and animals, the diversity, abundance and patterns of spread of antibiotic resistance genes (ARGs) in wildlife remains unclear. We identified 194 ARGs associated with phenotypic resistance to 13 types of antibiotic in meta-transcriptomic data generated from a broad range of lower vertebrates residing in both terrestrial and aquatic habitats. These ARGs, confirmed by PCR, included those that shared high sequence similarity to clinical isolates of public health concern. Notably, the lower vertebrate resistome varied by ecological niche of the host sampled. The resistomes in marine fish shared high similarity and were characterized by very high abundance, distinct from that observed in other habitats. An assessment of ARG mobility found that ARGs in marine fish were frequently co-localized with mobile elements, indicating that they were likely spread by horizontal gene transfer. Together, these data reveal the remarkable diversity and transcriptional levels of ARGs in lower vertebrates, and suggest that these wildlife species might play an important role in the global spread of ARGs.
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http://dx.doi.org/10.1038/s41598-020-75904-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608656PMC
November 2020

Metatranscriptomic Identification of Diverse and Divergent RNA Viruses in Green and Chlorarachniophyte Algae Cultures.

Viruses 2020 10 19;12(10). Epub 2020 Oct 19.

Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia.

Our knowledge of the diversity and evolution of the virosphere will likely increase dramatically with the study of microbial eukaryotes, including the microalgae within which few RNA viruses have been documented. By combining total RNA sequencing with sequence and structural-based homology detection, we identified 18 novel RNA viruses in cultured samples from two major groups of microbial algae: the chlorophytes and the chlorarachniophytes. Most of the RNA viruses identified in the green algae class Ulvophyceae were related to the and viral families commonly associated with land plants. This suggests that the evolutionary history of these viruses extends to divergence events between algae and land plants. Seven sp-associated viruses exhibited sequence similarity to the mitoviruses most commonly found in fungi, compatible with horizontal virus transfer between algae and fungi. We also document, for the first time, RNA viruses associated with chlorarachniophytes, including the first negative-sense (bunya-like) RNA virus in microalgae, as well as a distant homolog of the plant virus , potentially signifying viral inheritance from the secondary chloroplast endosymbiosis that marked the origin of the chlorarachniophytes. More broadly, these data suggest that the scarcity of RNA viruses in algae results from limited investigation rather than their absence.
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http://dx.doi.org/10.3390/v12101180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594059PMC
October 2020