Giant RNA genomes: Roles of host, translation elongation, genome architecture, and proteome in nidoviruses

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(7)

Опубликована: Фев. 10, 2025

Positive-strand RNA viruses of the order Nidovirales have largest known genomes vertebrate and invertebrate with 36.7 41.1 kb, respectively. The acquisition a proofreading exoribonuclease (ExoN) by an ancestral nidovirus enabled crossing 20 kb barrier. Other factors constraining genome size variations in nidoviruses remain poorly defined. We assemble 76 sequences from >500.000 published transcriptome experiments triple number >36 genomes, including 64 genome. Many identified viral lineages acquired putative enzymatic other protein domains linked to size, host phyla, or virus families. inserted may regulate replication virion formation, modulate infection otherwise. classify ExoN-encoding into seven groups four subgroups, according canonical noncanonical modes replicase expression ribosomes genomic organization (reModes). most-represented group employing reMode comprises nidoviruses, coronaviruses. Six reModes include 31-to-64 genomes. Among them are segmented utilizing dual ribosomal frameshifting that we validate experimentally. Moreover, polyprotein length show reMode- phylum-dependent relationships. hypothesize increase be limited host-inherent translation fidelity, ultimately setting limit. Thus, expansion vertebrate/invertebrate division, control expression, fidelity interconnected.

Язык: Английский

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Unleashing the Potential of Artificial Intelligence in Infectious Diseases

National Science Review, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Язык: Английский

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Impact of ornamentals for the one health concept during Anthropocene

Acta Horticulturae, Год журнала: 2025, Номер 1417, С. 149 - 156

Опубликована: Янв. 1, 2025

Язык: Английский

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Pathogen genomic surveillance and the AI revolution

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

ABSTRACT The unprecedented sequencing efforts during the COVID-19 pandemic paved way for genomic surveillance to become a powerful tool monitoring evolution of circulating viruses. Herein, we discuss how state-of-the-art artificial intelligence approach called protein language models (pLMs) can be used effectively analyzing pathogen data. We highlight examples pLMs applied predicting viral properties and lay out framework integrating into pipelines.

Язык: Английский

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Uncovering the hidden RNA virus diversity in Lake Nam Co: Evolutionary insights from an extreme high-altitude environment

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(6)

Опубликована: Фев. 4, 2025

Alpine lakes, characterized by isolation, low temperatures, oligotrophic conditions, and intense ultraviolet radiation, remain a poorly explored ecosystem for RNA viruses. Here, we present the first comprehensive metatranscriptomic study of viruses in Lake Nam Co, high-altitude alkaline saline lake on Tibetan Plateau. Using combination sequence- structure-based homology searches, identified 742 virus species, including 383 novel genus-level groups 84 family-level exclusively found Co. These findings significantly expand known diversity Orthornavirae , uncovering evolutionary adaptations such as permutated RNA-dependent polymerase motifs distinct secondary structures. Notably, 14 additional families potentially infecting prokaryotes were predicted, broadening host range questioning traditional assumption that predominantly target eukaryotes. The presence auxiliary metabolic genes viral genomes suggested (families f . 0102 Nam-Co_family_51) exploit energy production mechanisms energy-limited alpine lakes. Low nucleotide diversity, single polymorphism frequencies, pN/pS ratios indicate strong purifying selection Co populations. Our offer insights into evolution ecology, highlighting importance extreme environments hidden further shed light their potential ecological implications, particularly context climate change.

Язык: Английский

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Functional and evolutionary characterization of potential auxiliary metabolic genes of the global RNA virome

iMetaOmics., Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

We generated the first comprehensive view of RNA viral auxiliary metabolic genes (AMGs), expanding known functional type AMGs by 75%. viruses encode a remarkably high diversity AMGs, spanning 25 distinct categories. Most these are linked to environmental regulation and genetic information processing, with fewer associated nutrient cycling. Additionally, carrying capable infecting both eukaryotes prokaryotes, may acquire from organisms beyond their predicted host range. Viruses most abundant biological entities on Earth, exhibiting immense playing vital ecological roles [1]. They can influence crucial processes biogeochemical cycles altering metabolism via (AMGs) [2]. virus-encoded acquired sporadically present in phage genome relatively unknown degree [3]. sample during infection, subset horizontal gene transfer events will be kept if they augment or redirect important that provide sufficient adaptive advantages under specific conditions [4]. For decades, research has focused DNA genomes variety habitats—including humans, oceans, soils, wastewater treatment plants, extreme environments [5]—have revealed diverse functions ranging photosynthesis, carbon phosphate metabolism, nitrogen sulfur cycling, nucleic acid antioxidants, heavy metal detoxification [4, 6]. The development metatranscriptomic sequencing illuminated vast, untapped global viruses, revealing equally critical shaping communities, driving evolution, regulating [7]. key mechanism effects, remain largely unexplored, only few studies focusing [8-12]. significance however, poorly understood. By leveraging power newly available virome datasets—including Tara Oceans data set [10], Metatranscriptomes (RVMT) database [13], LucaProt resource [14]—this study provides phylogenetic analysis AMGs. addressing this gap ecology, we aim uncover functions, virus–host interactions, evolutionary dynamics scale. screening 3,216,257 (vContigs) datasets, identified 256 putative 225 vContigs (Figure S1, Table S1). Of 124 were assigned five established phyla: Lenarviricota (57, 25.3%), Pisuviricota (29, 12.9%), Kitrinoviricota Duplornaviricota (8, 3.6%), Negarnaviricota (1, 0.4%). 93 classified novel "Taraviricota" 0.4%) 13 supergroups (92, 40.9%) 1A). primarily consisted Picorna (36, 16.0%), Tombus-Noda (18, 8.0%), Supergroup022 3.6%) However, 8 (3.6%) remained unclassified. Among taxonomically Fiersviridae (34, 15.1%), Narnaviridae (12, 5.3%), Marnaviridae 5.3%) represented families S2, S2). Host predictions predominantly infect (66, 29.3%), including Opisthokonta (Fungi Metazoa) Viridiplantae (green plants). these, emerged as frequent eukaryotic group for 1A, Meanwhile, 44 (19.6%) belonged canonical prokaryotic Leviviricetes Vidaverviricetes [13]. hosts remaining 115 (51.1%) could not confidently assigned. involved 58 pathways S3), categorized into (69, 27.0%), (128, 50.0%), 11.3%) well cellular (13, 5.1%) organismal systems (3, 1.2%) 1B). These spanned categories, top four being translation (77, 30.1%), energy (24, 9.4%), membrane transport 7.0%), transcription 7.0%) 1C). category was ribosomal proteins (RPs) 1D), which ribosome assembly protein synthesis, rely entirely host's translational machinery. After selectively inhibit synthesis usurping endogenous increasing biosynthesis virus [15]. prevalence RPs highlights importance replication. Interestingly, found 18 encoded more than one AMG S4). Notable examples include 150DCM1MMQQ14_25606 152SUR2MMQQ14_439061, photosynthesis-related PsbC PsbD; vContig S11_len2823, SoxY SoxZ; ND_008319, oxidative phosphorylation AtpC AtpD, all central Furthermore, (TARA_131_DCM_0.22-3_k119_171980) enzymes (NapA, NirB, NirD), alongside RPS21, priming enzyme DnaG, suggesting numerous chaperone peripheral regulate environment sensing stress adaptation 1D). example, molecular (HtpG) ATP-dependent Clp protease (ClpP) increase cell tolerance temperatures [16]. flagellar formation enhance ability cells adhere, invade, nutrients avoiding hostile [17]. also remodel antioxidant network improve replication efficiency encoding several oxidoreductases (catalase, superoxide dismutase, peroxiredoxin, thioredoxin) scavenging reactive oxygen species Given close relationship between hosts, reflect adaptations conditions. living plant phyllosphere have VI secretion system (T6SS)-related (HCP ImpE) (Table help inhibiting pathogens responding abiotic stresses [18]. coproporphyrinogen III oxidase (CpoX), tetrapyrrole rhizosphere cpoX prevent light-dependent death promote its growth [19]. mammals enriched oligopeptide S1), mediate uptake dipeptides tripeptides animal it source [20]. In such soil activated sludge, antibiotic resistance like VanY, concentrations antibiotics habitats. To further investigate how impact cycles, representative selected analysis. (pyruvate kinase, pk; acyl carrier protein, acpP; S-adenosylmethionine metK; decarboxylase, speD), (nitrate reductase, napA; nitrite reductase large subunit, nirB; small nirD), (sulfur-oxidizing proteins, soxY soxZ), photosynthesis (photosystem II (PSII) D1 psbA; PSII D2 psbD; CP43 reaction center psbC; J, psbJ) 2, Figure S5). structure modeling showed confidence PK, AcpP, MetK, SpeD, NapA, NirD, SoxY, SoxZ, PsbA, PsbC, PsbD, PsbJ 98% Although NirB confirmed modeling, full amino sequence shares 100% identity NCBI reference (Accession No.: WP_105027197.1) S3). related carbon, nitrogen, phosphorus, contrast, none phosphorus restricted role cycling counterparts. range differences might contribute difference, eukaryotes, while mainly target bacteria archaea. potential sources them, constructed trees 30 types (62 sequences 51 vContigs) motility. Phylogenetic 36 27 originated 11 (Figures S6, S7A–K 19 vContigs, six prokaryotes S7L–P S4), infected identities indicated 26 24 origin, two (S11_len3866 ND_146864) SpeD S7A). 22 10 12 S8A–H Therefore, investigated had inconsistent according taxonomic classification. prediction uncultured is still challenging task. Recent lineages [9]. subsets picobirnaviruses partitiviruses eukaryote likely able propose represent prokaryote viruses. Alternatively, same hosts. During co-infection, form tripartite association obtain genes. addition, through HGT third organism. Finally, acknowledge some contigs result misassembles. While assembled de novo short reads risk chimeric assemblies low, cannot excluded. Future employing long-read efforts isolate essential resolving uncertainties shedding light host-virus interactions. preparation work, published preprints, included current paper [9, 12]. Compared studies, similar patterns observed environments, transcription, translation, signaling pathways, photosynthesis. widespread distribution emphasizes interactions ecosystems. datasets [9-12], 75.3% (140 out 186 different AMGs) new S5), significantly expands existing Currently, portion ecosystems covered studies. Together our predict greater uncovered sampling virome. Leveraging Our findings insights: (i) exhibit diversity, categories; (ii) those less common; (iii) prokaryotes; (iv) outside Collectively, understanding intricate play modulating ecosystem functions. Detailed procedures collection, identification annotation analysis, tree construction comprehensively described Supporting Information Methods, Figures S9–10 S6. Yang Zhao: Data curation; software; investigation; validation; visualization; writing—original draft; writing—review editing; methodology. Zhihao Zhang: Methodology; editing. Meiling Feng: Writing—review investigation. Rong Wen: Pengfei Liu: Conceptualization; methodology; funding acquisition; supervision. This work supported National Natural Science Foundation China Excellent Young Scientists Fund Program (42222105), General (42171144), Second Tibetan Plateau Scientific Expedition Research (STEP) (2021QZKK0100), Global Ocean Negative Carbon Emissions (Global ONCE) Program. apologize cite additional owing space limitations. authors declare no conflicts interest. No animals humans study. support corresponding author upon reasonable request. scripts used at https://github.com/YangZhao-LZU/RNA_AMG. Supplementary materials (methods, figures, tables, graphical abstract, slides, videos, Chinese translated version, update materials) online DOI iMeta http://www.imeta.science/imetaomics/. S1. Overview pipeline. S2. RdRps phyla. S3. distributed eight habitats pathways. S4. Network diagram multiple S5. involvement system. sources, S7. prokaryotes. S8. eukaryotes. S9. Genome architecture model. S10. RdRP three highly complete conserved motifs (A, B, C). Auxiliary detected dataset. linkage. Protein model 140 46 previously reported HHsuite results Please note: publisher responsible content functionality any supporting supplied authors. Any queries (other missing content) should directed article.

Язык: Английский

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The Vaginal Virome in Women’s Health and Disease

Microorganisms, Год журнала: 2025, Номер 13(2), С. 431 - 431

Опубликована: Фев. 16, 2025

Most research on the vaginal microbiome has focused bacterial communities (the bacteriome), but viruses, including eukaryotic viruses and bacteriophages, are also important players in health disease states. In this review, we will briefly discuss microbiome, delve into what is known about virome its impact women's health, finish with novel microbial or microbial-derived therapeutics horizon. More studies needed to better prevent treat gynecological, reproductive, neonatal diseases.

Язык: Английский

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ACE2 utilization of HKU25 clade MERS-related coronaviruses with broad geographic distribution

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Abstract Dipeptidyl peptidase-4 (DPP4) is a well-established receptor for several MERS-related coronaviruses (MERSr-CoVs) isolated from humans, camels, pangolins, and bats (1–6). However, the usage of many genetically diverse bat MERSr-CoVs with broad geographical distributions remains poorly understood. Recent studies have identified angiotensin-converting enzyme 2 (ACE2) as an entry multiple merbecovirus clades. Here, using viral antigen pseudovirus-based functional assays, we demonstrate that merbecoviruses HKU25 clade previously thought to utilize DPP4 (7), employ ACE2 their receptor. Cryo-electron microscopy analysis revealed HsItaly2011 VsCoV-a7 recognize binding mode sharing similarity HKU5 but involving remodeled interfaces distinct ortholog selectivity, suggesting common evolutionary origin utilization these two clades viruses. EjCoV-3, strain closely related DPP4-using MERSr-CoV BtCoV-422, exhibited relatively tropism could human albeit suboptimally. Despite differences in mechanisms spike proteolytic activation compared MERS-CoV, viruses remain sensitive broadly neutralizing antibodies inhibitors. These findings redefine our understanding evolution among highlight versatility coronaviruses. Significance unexpectedly convergently evolved modes across three continents, challenging dogma primary distributed Eurasia host through shared HKU5, prior findings. reveal prevalence show EjCoV-3 preadapted use ACE2, potential spillover. Our data provide blueprint barrier determinants which will facilitate global surveillance development countermeasures against characterized merbecoviruses.

Язык: Английский

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Informationsschatz aus Umweltproben

BIOspektrum, Год журнала: 2025, Номер 31(1), С. 59 - 62

Опубликована: Фев. 1, 2025

Язык: Английский

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How nidoviruses evolved the largest known RNA genomes

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(11)

Опубликована: Март 10, 2025

Emotions coordinate our behavior and physiological states during survival-salient events pleasurable interactions. Even though we are often consciously aware of current emotional state, such as anger or happiness, the mechanisms giving ...Emotions felt in body, somatosensory feedback has been proposed to trigger conscious experiences. Here reveal maps bodily sensations associated with different emotions using a unique topographical self-report method. In ...

Язык: Английский

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