Marine viruses discovered through metagenomics shed light on viral strategies throughout the oceans
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ABSTRACT:
PROVIDER: PRJEB19352 | ENA |
REPOSITORIES: ENA
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Project description:A grand challenge in biology is the lack of annotation for much of global sequence space. In particular, while microbes and their viruses are critical to Earth System functioning, surveys of their communities in nature routinely return genes of unknown function, particularly for viruses. This hampers understanding and predictive capability, and reflects a number of database limitations. Here we apply high-resolution environmental metaproteomics to 4 purified viral concentrates from the Tara Oceans Expedition to identify in situ proteins extracted from uncultivated viral particles. Using matched metagenomic databases, we identified 1875 proteins belonging to 549 non-redundant protein clusters that are predominantly of unknown function. These data help identify function for structure-associated proteins in known abundant tailed viruses (e.g., pelagiphages and cyanophages) and validate newly-identified uncultured viral sequences linked to abundant novel hosts. One protein cluster alone comprised 22% of the identified structure-associated proteins, with ~46% of the observed spectra. Structural modeling of this highly abundant viral protein cluster indicates its likely role as a novel, previously unknown capsid. Together these analyses provide much-needed, culture-independent structure-associated protein annotations critical for identifying viral signals across diverse datasets to better elucidate viral roles in nature.
2016-02-25 | PXD000938 | Pride
Project description:<p>Algal blooms are hotspots of primary production in the ocean, forming the basis of the marine food web and fueling the dissolved organic matter (DOM) pool. Marine viruses are key players in controlling algal bloom demise, thereby diverting algal biomass from higher trophic levels to the DOM pool, a process termed the ‘viral shunt’. To decode the metabolic footprint of the ‘viral shunt’ in the marine environment, we induced a bloom of <em>Emiliania huxleyi</em> and followed its succession using an untargeted exometabolomics approach. Here, we show that algal bloom succession induces dynamic changes in the exometabolic landscape. We discovered a set of novel chlorine-iodine-containing metabolites that were induced by viral infection and released during bloom demise. These metabolites were further detected in virus-infected oceanic <em>E. huxleyi</em> blooms. Therefore, we propose that halogenation with both chlorine and iodine is a distinct hallmark of the virus-induced DOM of <em>E. huxleyi</em>, providing insights into the metabolic consequences of the ‘viral shunt’ for marine DOM.</p>
2021-05-05 | MTBLS1720 | MetaboLights
Project description:Paramyxoviruses (PMVs) exploit the host's translation machinery to enhance their replication. We found that the PMV matrix protein is crucial in this process, inhibiting host protein synthesis while boosting viral protein production. This occurs through interactions with the core exon-junction complex (cEJC), a key player in mRNA biogenesis. Disruption of this interaction using siRNA led to increased viral replication but did not affect other viruses like SARS-CoV-2. Our study unveils a novel mechanism by which PMVs hijack host cell resources, offering new targets for antiviral therapy.
2024-10-09 | GSE274026 | GEO
Project description:Marine sponges are essential for coral reefs to thrive and harbour a diverse microbiome that is thought to contribute to host health. Although the overall function of sponge symbionts has been increasingly described, in-depth characterisation of each taxa remains challenging, with many sponge species hosting up to 3,000 distinct microbial species. Recently, the sponge Ianthella basta has emerged as a model organism for symbiosis research, hosting only three dominant symbionts: a Thaumarchaeotum, a Gammaproteobacterium, and an Alphaproteobacterium and a range of other minor taxa. Here, we retrieved metagenome assembled genomes (MAGs) for >90% of I. basta’s microbial community which allowed us to make a complete metabolic reconstruction of the sponge’s microbiome, identifying metabolic complementarity between microbes, as well as the importance of symbionts present in low abundance. We also mined the metagenomes for putative viral sequences, highlighting the contribution of viruses to the overall metabolism of the sponge, and complement this data with metaproteomic sequencing to identify active metabolic pathways in both prokaryotes and viruses. This data now allows us to use I. basta as a model organism for studying host-microbe interactions and provides a basis for future (genomic) manipulative experiments.
2023-02-24 | PXD032278 | Pride
Project description:The marine diatom Guinardia delicatula is a cosmopolitan species that dominates seasonal blooms in the English Channel and the North Sea. Several eukaryotic parasites are known to induce the mortality of this key-stone species. Here, we report the isolation and the characterization of the first viruses that infect G. delicatula. Viruses were isolated from the Western English Channel (SOMLIT-ASTAN station) during the late summer bloom decline of G. delicatula. A combination of laboratory approaches revealed that these lytic viruses (GdelRNAV) are small untailed particles of 35-38 nm in diameter that replicated in the host cytoplasm where both unordered particles and crystalline arrays were formed. GdelRNAV displayed a linear single-stranded RNA genome of ~9 kb, including two open reading frames encoding for replication and structural polyproteins. Phylogenetic relationships based on the RNA-dependent-RNA-polymerase gene marker showed that GdelRNAV were new members of the Bacillarnavirus, a monophyletic genus belonging to the order Picornavirales. GdelRNAV were specific to several strains of G. delicatula, they were produced rapidly (< 12h) and in numbers (9.34 x 104 virions per host cell). We recorded a substantial delay (72 h) between virions release and host cell lysis. Our analysis points to variable viral susceptibilities of the host during the early exponential growth phase. Interestingly, we consistently failed to isolate viruses during spring and early summer while G. delicatula developed rapid and massive blooms. While our study suggests that viruses do contribute to the decline of G. delicatula late summer bloom, they may not be the primary mortality agents during the remaining blooms at SOMLIT-ASTAN. Future studies should focus on the relative contribution of the viral and eukaryotic pathogens to the control of Guinardia blooms to understand the fate of these prominent organisms in marine systems.
2019-01-30 | PXD010967 | Pride
Project description:Previous studies have demonstrated that the iron content in marine heterotrophic bacteria is comparatively higher than that of phytoplankton. Therefore, they have been indicated to play a major role in the biogeochemical cycling of iron. In this study, we aimed to investigate the potential of viral lysis as a source of iron for marine heterotrophic bacteria. Viral lysates were derived from the marine heterotrophic bacterium, Vibrio natriegens PWH3a (A.K.A Vibrio alginolyticus). The bioavailability of Fe in the lysates was determined using a model heterotrophic bacterium, namely, Dokdonia sp. strain Dokd-P16, isolated from Fe-limited waters along Line P transect in the Northeastern Pacific Ocean. The bacteria were grown under Fe-deplete or Fe-replete conditions before being exposed to the viral lysate. Differential gene expression following exposure to the viral lysate was analyzed via RNA sequencing to identify differentially expressed genes under iron-replete and iron-deplete conditions. This study would provide novel insights into the role of viral lysis in heterotrophic bacteria in supplying bioavailable iron to other marine microorganisms under iron-limiting and non-limiting conditions. First, the marine heterotrophic bacterium genome, Dokdonia sp. strain Dokd-P16, was sequenced to provide a genomic context for the expression studies. Subsequently, the relative gene expression in Dokdonia sp. strain Dokd-P16 grown under Fe limiting and non-limiting conditions were analyzed. This transcriptomic approach would be utilized to elucidate genes regulated by Fe availability in Dokdonia sp. strain Dokd-P16, which indicate its Fe-related response viral lysate exposure. Taken together, in this study, the transcriptomic responses of Fe-limited and non-limited marine heterotrophic bacteria were analyzed, which provided novel insights into the biological availability of Fe from the viral lysates.
2021-11-01 | GSE166618 | GEO
Project description:This mathematical model of the role of the innate immune responses generated by macrophages in the context of anti-tumour oncolytic viral therapies is described in the publication:
Nada Almuallem, Dumitru Trucu, Raluca Eftimie. "Oncolytic viral therapies and the delicate balance between virus-macrophage-tumour interactions: A mathematical approach". Mathematical Biosciences and Engineering, 2021, 18(1): 764-799.
doi: 10.3934/mbe.2021041
Comment:
This model is represented by Equations 2.1a-f of the publication manuscript.
Abstract:
The success of oncolytic virotherapies depends on the tumour microenvironment, which contains a large number of infiltrating immune cells. In this theoretical study, we derive an ODE model to investigate the interactions between breast cancer tumour cells, an oncolytic virus (Vesicular Stomatitis Virus), and tumour-infiltrating macrophages with different phenotypes which can impact the dynamics of oncolytic viruses. The complexity of the model requires a combined analytical-numerical approach to understand the transient and asymptotic dynamics of this model. We use this model to propose new biological hypotheses regarding the impact on tumour elimination/relapse/persistence of: (i) different macrophage polarisation/re-polarisation rates; (ii) different infection rates of macrophages and tumour cells with the oncolytic virus; (iii) different viral burst sizes for macrophages and tumour cells. We show that increasing the rate at which the oncolytic virus infects the tumour cells can delay tumour relapse and even eliminate tumour. Increasing the rate at which the oncolytic virus particles infect the macrophages can trigger transitions between steady-state dynamics and oscillatory dynamics, but it does not lead to tumour elimination unless the tumour infection rate is also very large. Moreover, we confirm numerically that a large tumour-induced M1→M2 polarisation leads to fast tumour growth and fast relapse (if the tumour was reduced before by a strong anti-tumour immune and viral response). The increase in viral-induced M2→M1 re-polarisation reduces temporarily the tumour size, but does not lead to tumour elimination. Finally, we show numerically that the tumour size is more sensitive to the production of viruses by the infected macrophages.
2024-09-02 | BIOMD0000001033 | BioModels
Project description:As intracellular parasites, viruses exploit cellular proteins at every stage of infection. Adenovirus related outbreaks cause severe acute respiratory illnesses and conjunctivitis, with no specific antiviral therapy yet available. Herein, we investigate human adenovirus (HAdV-D37) pIIIa-host protein interactions by affinity purification and mass spectrometry (AP-MS) screens. We demonstrate that viral pIIIa interacts with ubiquitin-specific protease 9x (USP9x) and Ran-binding protein 2 (RANBP2). As intracellular parasites, viruses exploit cellular proteins at every stage of infection. Adenovirus related outbreaks cause severe acute respiratory illnesses and conjunctivitis, with no specific antiviral therapy yet available. Herein, we investigate human adenovirus (HAdV-D37) pIIIa-host protein interactions by affinity purification and mass spectrometry (AP-MS) screens. We demonstrate that viral pIIIa interacts with ubiquitin-specific protease 9x (USP9x) and Ran-binding protein 2 (RANBP2).
2022-05-30 | PXD023642 | Pride
Project description:In healthy individuals, immune control of persistent human cytomegalovirus (HCMV) infection is effectively mediated by virus-specific CD4+ and CD8+ T cells. However, identification of the repertoire of T-cell specificities for HCMV is hampered by the immense protein coding capacity of this betaherpesvirus. We applied a novel approach which employs HCMV deletion mutant viruses, lacking HLA class I immunoevasins. Infection of human fibroblast cell lines with those mutant viruses allowed the direct identification of naturally presented HCMV-derived HLA ligands by mass spectrometry. Using this strategy, we identified 368 unique HCMV-derived HLA class I ligands representing an unexpectedly broad panel of 123 HCMV antigens. Functional characterization revealed memory T-cell responses in seropositive individuals for a substantial proportion (28%) of these novel peptides. The unbiased identification of naturally presented viral epitopes enabled a comprehensive and systematic assessment of the physiological repertoire of anti-HCMV T-cell specificities in seropositive individuals. This approach proved to be superior to procedures applying in silico analysis to identify true viral antigens.
2019-11-20 | PXD013120 | Pride
Project description:Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigated the antiviral RNA interference (RNAi) pathway in bat cells and discovered that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs (vsiRNAs) upon Sindbis virus (SINV) infection that were missing in human cells. Disruption of Dicer function resulted in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors (PRRs), such as retinoic acid-inducible gene I (RIG-I), with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.
2024-07-12 | GSE221607 | GEO