Publications by authors named "Joan Martí-Carreras"

11 Publications

  • Page 1 of 1

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes.

Emerg Infect Dis 2021 Jan;27(1):76-84

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus-infected patients. We studied the relationship between KIR-human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4-003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4-003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.
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http://dx.doi.org/10.3201/eid2701.202177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774578PMC
January 2021

NCBI's Virus Discovery Codeathon: Building "FIVE" -The Federated Index of Viral Experiments API Index.

Viruses 2020 12 10;12(12). Epub 2020 Dec 10.

National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20894, USA.

Viruses represent important test cases for data federation due to their genome size and the rapid increase in sequence data in publicly available databases. However, some consequences of previously decentralized (unfederated) data are lack of consensus or comparisons between feature annotations. Unifying or displaying alternative annotations should be a priority both for communities with robust entry representation and for nascent communities with burgeoning data sources. To this end, during this three-day continuation of the Virus Hunting Toolkit codeathon series (VHT-2), a new integrated and federated viral index was elaborated. This Federated Index of Viral Experiments (FIVE) integrates pre-existing and novel functional and taxonomy annotations and virus-host pairings. Variability in the context of viral genomic diversity is often overlooked in virus databases. As a proof-of-concept, FIVE was the first attempt to include viral genome variation for HIV, the most well-studied human pathogen, through viral genome diversity graphs. As per the publication of this manuscript, FIVE is the first implementation of a virus-specific federated index of such scope. FIVE is coded in BigQuery for optimal access of large quantities of data and is publicly accessible. Many projects of database or index federation fail to provide easier alternatives to access or query information. To this end, a Python API query system was developed to enhance the accessibility of FIVE.
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http://dx.doi.org/10.3390/v12121424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764237PMC
December 2020

A Phylodynamic Workflow to Rapidly Gain Insights into the Dispersal History and Dynamics of SARS-CoV-2 Lineages.

Mol Biol Evol 2020 Nov 3. Epub 2020 Nov 3.

Laboratory of Clinical and Epidemiological Virology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of SARS-CoV-2 have been generated and shared with the scientific community. The unparalleled volume of available genetic data presents a unique opportunity to gain real-time insights into the virus transmission during the pandemic, but also a daunting computational hurdle if analyzed with gold-standard phylogeographic approaches. To tackle this practical limitation, we here describe and apply a rapid analytical pipeline to analyze the spatiotemporal dispersal history and dynamics of SARS-CoV-2 lineages. As a proof of concept, we focus on the Belgian epidemic, which has had one of the highest spatial densities of available SARS-CoV-2 genomes. Our pipeline has the potential to be quickly applied to other countries or regions, with key benefits in complementing epidemiological analyses in assessing the impact of intervention measures or their progressive easement.
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http://dx.doi.org/10.1093/molbev/msaa284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665608PMC
November 2020

STAT2 signaling restricts viral dissemination but drives severe pneumonia in SARS-CoV-2 infected hamsters.

Nat Commun 2020 11 17;11(1):5838. Epub 2020 Nov 17.

Laboratory of Virology and Chemotherapy, Rega Institute, KU Leuven Department of Microbiology, Immunology and Transplantation, 3000, Leuven, Belgium.

Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.
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http://dx.doi.org/10.1038/s41467-020-19684-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672082PMC
November 2020

Preparedness needs research: How fundamental science and international collaboration accelerated the response to COVID-19.

PLoS Pathog 2020 10 9;16(10):e1008902. Epub 2020 Oct 9.

Laboratory of Clinical and Epidemiological Virology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

The first cluster of patients suffering from coronavirus disease 2019 (COVID-19) was identified on December 21, 2019, and as of July 29, 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been linked with 664,333 deaths and number at least 16,932,996 worldwide. Unprecedented in global societal impact, the COVID-19 pandemic has tested local, national, and international preparedness for viral outbreaks to the limits. Just as it will be vital to identify missed opportunities and improve contingency planning for future outbreaks, we must also highlight key successes and build on them. Concomitant to the emergence of a novel viral disease, there is a 'research and development gap' that poses a threat to the overall pace and quality of outbreak response during its most crucial early phase. Here, we outline key components of an adequate research response to novel viral outbreaks using the example of SARS-CoV-2. We highlight the exceptional recent progress made in fundamental science, resulting in the fastest scientific response to a major infectious disease outbreak or pandemic. We underline the vital role of the international research community, from the implementation of diagnostics and contact tracing procedures to the collective search for vaccines and antiviral therapies, sustained by unique information sharing efforts.
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http://dx.doi.org/10.1371/journal.ppat.1008902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546461PMC
October 2020

BKTyper: Free Online Tool for Polyoma BK Virus VP1 and NCCR Typing.

Viruses 2020 07 31;12(8). Epub 2020 Jul 31.

Laboratory of Clinical and Epidemiological Virology, Department of Microbiology, Immunology and Transplantation, Rega Institute, Zoonotic Infectious Diseases Unit, KU Leuven, BE3000 Leuven, Belgium.

Human BK polyomavirus (BKPyV) prevalence has been increasing due to the introduction of more potent immunosuppressive agents in transplant recipients, and its clinical interest. BKPyV has been linked mostly to polyomavirus-associated hemorrhagic cystitis, in allogenic hematopoietic stem cell transplant, and polyomavirus-associated nephropathy in kidney transplant patients. BKPyV is a circular double-stranded DNA virus that encodes for seven proteins, of which Viral Protein 1 (VP1), the major structural protein, has been extensively used for genotyping. BKPyV also contains the noncoding control region (NCCR), configured by five repeat blocks (OPQRS) known to be highly repetitive and diverse, and linked to viral infectivity and replication. BKPyV genetic diversity has been mainly studied based on the NCCR and , due to the high occurrence of BKPyV-associated diseases in transplant patients and their clinical implications. Here BKTyper is presented, a free online genotyper for BKPyV, based on a genotyping and a novel algorithm for NCCR block identification. genotyping is based on a modified implementation of the (BKTGR) algorithm, providing a maximum-likelihood phylogenetic tree using a custom internal BKPyV database. Novel NCCR block identification relies on a minimum of 12-bp motif recognition and a novel sorting algorithm. A graphical representation of the OPQRS block organization is provided.
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http://dx.doi.org/10.3390/v12080837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472310PMC
July 2020

Accounting for population structure reveals ambiguity in the Zaire Ebolavirus reservoir dynamics.

PLoS Negl Trop Dis 2020 03 4;14(3):e0008117. Epub 2020 Mar 4.

KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Division of Clinical and Epidemiological Virology, Leuven, Belgium.

Ebolaviruses pose a substantial threat to wildlife populations and to public health in Africa. Evolutionary analyses of virus genome sequences can contribute significantly to elucidate the origin of new outbreaks, which can help guide surveillance efforts. The reconstructed between-outbreak evolutionary history of Zaire ebolavirus so far has been highly consistent. By removing the confounding impact of population growth bursts during local outbreaks on the free mixing assumption that underlies coalescent-based demographic reconstructions, we find-contrary to what previous results indicated-that the circulation dynamics of Ebola virus in its animal reservoir are highly uncertain. Our findings also accentuate the need for a more fine-grained picture of the Ebola virus diversity in its reservoir to reliably infer the reservoir origin of outbreak lineages. In addition, the recent appearance of slower-evolving variants is in line with latency as a survival mechanism and with bats as the natural reservoir host.
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http://dx.doi.org/10.1371/journal.pntd.0008117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075637PMC
March 2020

Drosophila Interspecific Hybridization Causes A Deregulation of the piRNA Pathway Genes.

Genes (Basel) 2020 02 19;11(2). Epub 2020 Feb 19.

Grup de Genòmica, Bioinformàtica i Biologia Evolutiva, Departament de Genètica i Microbiologia (Edifici C), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

Almost all eukaryotes have transposable elements (TEs) against which they have developed defense mechanisms. In the Drosophila germline, the main transposable element (TE) regulation pathway is mediated by specific Piwi-interacting small RNAs (piRNAs). Nonetheless, for unknown reasons, TEs sometimes escape cellular control during interspecific hybridization processes. Because the piRNA pathway genes are involved in piRNA biogenesis and TE control, we sequenced and characterized nine key genes from this pathway in and species and studied their expression pattern in ovaries of both species and their F1 hybrids. We found that gene structure is, in general, maintained between both species and that two genes- and are under positive selection. Three genes- and -displayed higher expression values in hybrids than both parental species, while others had RNA levels similar to the parental species with the highest expression. This suggests that the overexpression of some piRNA pathway genes can be a primary response to hybrid stress. Therefore, these results reinforce the hypothesis that TE deregulation may be due to the protein incompatibility caused by the rapid evolution of these genes, leading to a TE silencing failure, rather than to an underexpression of piRNA pathway genes.
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http://dx.doi.org/10.3390/genes11020215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073935PMC
February 2020

NCBI's Virus Discovery Hackathon: Engaging Research Communities to Identify Cloud Infrastructure Requirements.

Genes (Basel) 2019 09 16;10(9). Epub 2019 Sep 16.

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda MD 20894, USA.

A wealth of viral data sits untapped in publicly available metagenomic data sets when it might be extracted to create a usable index for the virological research community. We hypothesized that work of this complexity and scale could be done in a hackathon setting. Ten teams comprised of over 40 participants from six countries, assembled to create a crowd-sourced set of analysis and processing pipelines for a complex biological data set in a three-day event on the San Diego State University campus starting 9 January 2019. Prior to the hackathon, 141,676 metagenomic data sets from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) were pre-assembled into contiguous assemblies (contigs) by NCBI staff. During the hackathon, a subset consisting of 2953 SRA data sets (approximately 55 million contigs) was selected, which were further filtered for a minimal length of 1 kb. This resulted in 4.2 million (Mio) contigs, which were aligned using BLAST against all known virus genomes, phylogenetically clustered and assigned metadata. Out of the 4.2 Mio contigs, 360,000 contigs were labeled with domains and an additional subset containing 4400 contigs was screened for virus or virus-like genes. The work yielded valuable insights into both SRA data and the cloud infrastructure required to support such efforts, revealing analysis bottlenecks and possible workarounds thereof. Mainly: (i) Conservative assemblies of SRA data improves initial analysis steps; (ii) existing bioinformatic software with weak multithreading/multicore support can be elevated by wrapper scripts to use all cores within a computing node; (iii) redesigning existing bioinformatic algorithms for a cloud infrastructure to facilitate its use for a wider audience; and (iv) a cloud infrastructure allows a diverse group of researchers to collaborate effectively. The scientific findings will be extended during a follow-up event. Here, we present the applied workflows, initial results, and lessons learned from the hackathon.
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http://dx.doi.org/10.3390/genes10090714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771016PMC
September 2019

Complete Genome Sequence of a New Ebola Virus Strain Isolated during the 2017 Likati Outbreak in the Democratic Republic of the Congo.

Microbiol Resour Announc 2019 May 16;8(20). Epub 2019 May 16.

KU Leuven, Department of Microbiology, Immunology and Transplantation, Clinical and Epidemiological Virology Division, Rega Institute, Leuven, Belgium

Genomic sequencing for early identification of Ebola virus remains a big challenge in low-income countries. Here, we report the complete genome sequence of an Ebola virus strain obtained during the 2017 Likati outbreak in the Democratic Republic of the Congo (DRC) by using the Oxford Nanopore Technologies (ONT) MinION sequencer.
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http://dx.doi.org/10.1128/MRA.00360-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522791PMC
May 2019

Human cytomegalovirus genomics and transcriptomics through the lens of next-generation sequencing: revision and future challenges.

Virus Genes 2019 Apr 2;55(2):138-164. Epub 2019 Jan 2.

Zoonotic Infectious Diseases Unit, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Herestraat 49, Box 1040, 3000, Leuven, Belgium.

The human cytomegalovirus (HCMV) genome was sequenced by hierarchical shotgun almost 30 years ago. Over these years, low and high passaged strains have been sequenced, improving, albeit still far from complete, the understanding of the coding potential, expression dynamics and diversity of wild-type HCMV strains. Next-generation sequencing (NGS) platforms have enabled a huge advancement, facilitating the comparison of differentially passaged strains, challenging diagnostics and research based on a single or reduced gene set genotyping. In addition, it allowed to link genetic features to different viral phenotypes as for example, correlating large genomic re-arrangements to viral attenuation or different mutations to antiviral resistance and cell tropism. NGS platforms provided the first high-resolution experiments to HCMV dynamics, allowing the study of intra-host viral population structures and the description of rare transcriptional events. Long-read sequencing has recently become available, helping to identify new genomic re-arrangements, partially accounting for the genetic variability displayed in clinical isolates, as well as, in changing the understanding of the HCMV transcriptome. Better knowledge of the transcriptome resulted in a vast number of new splicing events and alternative transcripts, although most of them still need additional validation. This review summarizes the sequencing efforts reached so far, discussing its approaches and providing a revision and new nuances on HCMV sequence variability in the sequencing field.
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http://dx.doi.org/10.1007/s11262-018-1627-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458973PMC
April 2019