Biology subjects

Guo, L.

Publications and source records attributed to Guo, L..

At least 73 records · Page 4Linked to original sources

bioRxiv2025

Metagenomic analysis of antimicrobial resistance, virulence, and mobile genetic elements in the gut microbiota of Caprinae species

The gut microbiota of livestock serves as a reservoir for antimicrobial resistance (AMR), yet Caprinae species remain understudied in this context. In this comprehensive metagenomic study, we analyzed 779 gut samples from Caprinae animals and reconstructed 17,023 high-quality metagenome-assembled genomes (MAGs). From these, we identified 4,685 antimicrobial resistance genes (ARGs) and 5,401 virulence factor genes (VFGs). Escherichia coli emerged as a major host carrying high burdens of both ARGs and VFGs. Strong positive correlations between ARGs, VFGs, and mobile genetic elements (MGEs) suggest potential co-selection and genetic linkage. Although MGEs were found in only 1.45% of MAGs, 23 ARGs were physically co-located with MGEs, indicating mobility potential. Additionally, three ARGs were embedded within viral genomes, two of which were associated with Myoviridae phages and one with an unclassified viral source, implicating phages in AMR dissemination. Comparative analyses revealed 292 ARG types shared between Caprinae and the human gut microbiota, including 20 genes representing six clinically critical resistance types: tetX1, tetX4, tmexD3, vanD, vanR, and vanS--conferring resistance to tigecycline, vancomycin, and polymyxins. These findings expand our understanding of the resistome and virulome in Caprinae animals and highlight potential zoonotic transmission pathways, underscoring the need for targeted AMR surveillance and mitigation strategies.

microbiology↗

bioRxiv2025

High-resolution in situ structures of hantavirus glycoprotein tetramers

SUMMARY/ABSTRACTNew World hantaviruses cause severe infections in humans, with case fatality rates approaching 40%. Previous structural studies have advanced our understanding of hantavirus glycoprotein architecture and function, however, the lack of high-resolution in situ structures of the glycoprotein tetramer and its lattice organization has limited mechanistic insights into viral assembly, entry, and antigenicity. Here, we leveraged a virus-like particle (VLP) system to establish a cryo-electron microscopy workflow for lattice-forming viral glycoproteins. This enabled the determination of a 2.35 [A] resolution structure of the membrane-embedded Andes virus (ANDV) glycoprotein tetramer, as well as structures of dimers of tetramers and a complex with antibody ADI-65534. These structures reveal previously uncharacterized features of glycoprotein organization, stability, and pH-sensing. Immunization of mice with self-amplifying replicon RNA (repRNA) encoding ANDV-VLPs elicited high levels of glycoprotein-binding antibodies but equivalent titers of neutralizing antibodies compared to repRNA-encoded native ANDV glycoprotein complex. Collectively, these findings advance our understanding of hantavirus glycoprotein assemblies and their function, laying a foundation for structure-based vaccine design efforts.

microbiology↗

bioRxiv2025

AAV gene therapy for GBA-PD and Gaucher Disease

Mutations in GBA1, the gene encoding glucocerebrosidase (GCase), are the most common risk factor for Parkinsons Disease (PD). GBA-PD patients are a genetic subpopulation of PD carrying heterozygous mutations in GBA1. Additionally, bi-allelic mutations in GBA1 cause Gaucher Disease (GD), a lysosomal storage disorder. Loss of GCase activity, a lysosomal enzyme leads to the accumulation of lipid substrates, disrupting lipid homeostasis and promoting cellular toxicity. Here, we report an AAV-mediated GBA1 replacement strategy to treat GD and GBA-PD by a one-time infusion via intravenous (GD Type 1) or intra-CSF (GBA-PD) route of administration. We engineered human GCase to be readily secretable to facilitate broad cross-correction. We developed CBE (conduritol {beta}-epoxide) induced lipid accumulation models to assess efficacy in mice and non-human primates (NHPs) to assess efficacy of our engineered constructs. Based on data across species, across different routes of administration, we nominated AAV.GMU01 SS3-GBA1 as our lead candidate. SS3-GBA1 is robustly secreted, cross-corrected across tissues and promotes lipid clearance. By comparing human GCase levels in AAV-treated NHP brains to healthy human donor brains, we demonstrate that AAV.GMU01 SS3-GBA1 replenishes the GCase deficit seen in GBA-PD patients, thus, restoring GCase to near-physiological levels Importantly, AAV.GMU01 SS3-GBA1 is well-tolerated with no adverse findings. Collectively, we establish a therapeutic strategy for the treatment of Gaucher Disease and GBA-PD with a single gene therapy product. One Sentence SummaryA novel gene therapy strategy for GBA1-PD and Gaucher disease with an engineered payload that robustly cross-corrects enhancing therapeutic footprint

neuroscience↗

bioRxiv2025

Integrating Multimodal Data for a Comprehensive Knowledge Graph to Advance Infectious Disease Research

Infectious diseases remain a formidable threat to global public health, with their escalating morbidity and mortality rates compounded by recurrent epidemics and the alarming rise of antimicrobial resistance (AMR). These challenges have intensified the urgent demand for innovative therapeutic strategies that can accelerate drug development cycles and overcome traditional research bottlenecks. To address these critical needs, we present IDKG (Infectious Disease Knowledge Graph), a specialized large-scale biomedical knowledge network designed to bridge data fragmentation through multimodal data integration. The IDKG constructs comprehensive associations from 345 infectious diseases and 708 pathogens across heterogeneous biomedical sources systematically. The graph architecture comprises nearly 50,000 nodes (8 types, including Pathogen, Protein, etc.) and over 1.2 million edges (11 types, including treats, contains, etc.), establishing an interconnected framework that enables systematic interrogation of cross-disciplinary knowledge. The integrative approach effectively dismantles conventional data silos while preserving biological contextuality. We validated the IDKGs potential by applying graph neural network-based approaches for drug repurposing prediction in human metapneumovirus (hMPV) infection, a common acute respiratory infection for which effective specific antiviral drugs are currently absent. The successfully identification of established antiviral agents, such as ribavirin and emetine, by our M1 model demonstrated its predictive accuracy and biological relevance. IDKG unifies multimodal biomedical data into a network to accelerate drug discovery and bolster outbreak response. This establishes a data-driven, knowledge-based paradigm for infectious disease research. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/657361v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@f5dc24org.highwire.dtl.DTLVardef@147d584org.highwire.dtl.DTLVardef@113083corg.highwire.dtl.DTLVardef@81d523_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

De novo design of protein-binding aptamers through deep reinforcement learning assembly of nucleic acid fragments

Nucleic acid aptamers targeting proteins are becoming increasingly important in biopharmaceuticals and molecular diagnostics. Traditionally, aptamers are discovered through labor-intensive screening of nucleic acid libraries using the SELEX method. However, de novo design approaches without experimental screening remain a significant challenge. Here, we employed deep reinforcement learning to develop an artificial intelligence (AI) agent capable of de novo aptamer design, termed AiDTA (AI-driven Docking-Then-Assembling). First, nucleic acid fragments were docked to the target protein to identify target-binding fragments. Then, AiDTA automatically assembled these fragments into aptamers using the Monte Carlo tree search algorithm and a policy-value neural network to guide the agent in generating aptamers with secondary structures similar to the original constituent fragments. Experimental validation demonstrated that the AiDTA-designed DNA aptamers targeting disease-related proteins exhibited high binding affinities in the nanomolar range, achieving the de novo design of protein-binding aptamers for the first time. Our study establishes a new approach to obtaining protein-binding aptamers for potential applications in biopharmaceuticals and diagnostics.

bioinformatics↗

bioRxiv2025

Th9-endothelial cell crosstalk promotes inflammatory atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death, and understanding its pathogenic drivers is critical for effective prevention and treatment. Inflammation has a critical role in ASCVD, and patients with inflammatory diseases are at increased risk. However, the key inflammatory mediator promoting ASCVD are incompletely understood, a major barrier when targeting inflammation to prevent ASCVD. Here, we found that interleukin-9 (IL-9) producing T helper cells (Th9) were significantly associated with ASCVD in patients with the autoimmune disease psoriasis. Th9 cells were poised to migrate to coronary vessels and were identified in atherosclerotic plaque. In vivo, murine inflammatory atherogenesis was prevented by IL-9 blockade and by IL-9 receptor (IL-9R) deletion in endothelial cells. In human arterial endothelial cells, IL-9R/STAT3 signaling promoted endothelial dysfunction, angiogenesis, and release of leukocyte chemoattractants. These findings suggest that in autoimmune diseases like psoriasis, Th9/IL-9 promote atherosclerosis by directly targeting endothelial cells, and that IL-9R/STAT3 signaling could be a promising therapeutic target for ASCVD. eTOC SummaryBaral et. al. investigate individuals who are at high risk for atherosclerosis due to underlying inflammatory disease and use mouse models of cardiovascular disease to uncover a role for interleukin-9-producing T helper 9 cells in the pathogenesis of inflammatory atherosclerosis.

immunology↗

bioRxiv2025

Grapevine phyllosphere pan-metagenomics reveals pan-microbiome structure, diversity, and functional roles in downy mildew resistance

Grapevines are among the most economically important fruit crops, and microbiome profoundly influence their health, yield, and quality. However, mechanistic insights into microbiome-orchestrated grapevine biology remain limited. Here, we conduct large-scale pan-metagenomic and pan-metatranscriptomic analyses of the phyllosphere microbiome from 107 grapevine accessions spanning 34 Vitis species. We show that the grapevine core microbiome is dominated by phylum Bacillota and Pseudomonadota. Leveraging PacBio sequencing, we assembled 19 high-quality metagenome-assembled genomes (MAGs) from the grapevine pan-microbiome, representing the first MAG reconstruction in plant-associated microbial communities using PacBio reads. These MAGs encode genes associated with antibiotic resistance, secondary metabolism, and carbohydrate-active enzymes (CAZymes), which could potentially influence grapevine biology. During downy mildew (DM) infection, DM-resistant grapevines exhibit significantly higher microbial network complexity than susceptible counterparts. Among the key taxa contributing to this complexity, Bacillota emerged as the dominant phylum with displaying strong abundance correlations with phylum Euglenozoa and Cyanobacteriota, and an isolated Bacillota species from the grapevine leaves, Bacillus cereus, demonstrated potent biocontrol activity against DM infection. Pan-metatranscriptomic analysis further revealed significant upregulation of eukaryotic microbial genes involved in primary and secondary metabolism. This pan-metagenomic study offers unprecedented insights into the complex structure, diversity and functional roles of grapevine phyllosphere microbiome, and presents valuable genomic and microbial resources for microbiome research and engineering to enhance viticulture productivity and quality.

microbiology↗

bioRxiv2025

IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity against neuroblastoma

Invariant natural killer T cells (NKTs) have intrinsic anti-tumor properties that make them promising candidates for chimeric antigen receptor (CAR)-based immunotherapies. Transgenic cytokine expression has been shown to enhance the potency of cellular immunotherapies, and we hypothesized that co-expressing IL-18 alone or with IL-15 would boost CAR-NKT therapeutic potential. To test this hypothesis, we generated retroviral constructs expressing IL-15 and/or IL-18 with the inducible caspase 9 (iC9) safety switch and co-transduced them with a GD2-specific CAR into human NKTs. Co-expression of IL-18 or IL-15/IL-18 increased GD2.CAR-NKT in vitro cytotoxicity, proliferation, and cytokine secretion compared to IL-15 alone. In a metastatic neuroblastoma model, GD2.CAR-NKTs expressing constructs with IL-18 controlled tumor growth better than cells expressing IL-15 only, but mice in the IL-15/IL-18 group developed severe toxicities not observed in the IL-18-only group. Mechanistically, we found that IL-18 drives a distinct transcriptional profile from IL-15 in CAR-NKTs marked by lower expression of exhaustion gene signatures and enrichment of metabolism-related processes. Finally, targeted metabolomics revealed that IL-18 induces broad metabolic reprogramming in CAR-NKTs including enhancement of oxidative phosphorylation, glycolysis, glutaminolysis and purine metabolism. These results support the use of IL-18 in developing the next generation of cytokine-armed CAR-NKT cancer immunotherapy.

immunology↗

bioRxiv2025

SND1 Impairs Calcium Homeostasis in Right Ventricular Failure by Binding and Destabilizing SERCA2a in Cardiomyocytes

BackgroundRight ventricular failure (RVF) is a major contributor to a poor prognosis in patients with pulmonary arterial hypertension (PAH); however, its underlying molecular mechanisms remain incompletely understood. We identified a significant upregulation of the cardiac fetal gene SND1 in the right ventricular myocardium of RVF rats. This upregulation may be a key component of cardiac fetal reprogramming and play a critical role in RVF progression. However, the precise molecular mechanisms by which SND1 contributes to RVF remain unelucidated. MethodsRat models of PAH were established by intraperitoneal injection of monocrotaline (MCT). The pulmonary artery pressure and right ventricular function of rats were assessed using transthoracic echocardiography combined with right heart catheterization. Weighted gene co-expression network analysis (WGCNA) of proteomic data identified a significant association between SND1 upregulation and RVF progression. Calcium transient and contractility measurements in single cardiomyocytes were performed to evaluate the effect of SND1 on sarcoplasmic reticulum (SR) function. Liquid chromatography with mass spectrometry/mass spectrometry analysis combined with co-immunoprecipitation (Co-IP) was used to identify sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2A (SERCA2a) as the protein interacting with SND1. The effect of SND1 on the progression of RVF was validated using cardiomyocyte-specific SND1 conditional knockout rats. ResultsProteomic and molecular analyses revealed that the cardiac fetal gene SND1 is reactivated in RVF and may contribute to disease progression. In vitro, SND1 knockdown in neonatal rat ventricular myocytes (NRVMs) enhanced contractility, improved calcium transient amplitude and velocity, and increased cell survival under calcium overload. Mechanistically, SND1 interacts with SERCA2a and promotes its proteasomal degradation, impairing SR calcium reuptake. SND1 knockdown restored SERCA2a stability. In vivo, cardiomyocyte-specific SND1 knockout improved right ventricular function, reduced SERCA2a degradation and apoptosis, and increased survival in RVF rats. ConclusionOur study revealed that SND1 reactivation (a fetal gene) contributes to the progression of RVF by promoting SERCA2a degradation and impairing calcium handling. Targeted suppression of SND1 enhances cardiomyocyte contractility and survival, highlighting SND1 as a potential therapeutic target for improving right ventricular function in PAH. Clinical perspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIThis study identifies SND1, a reactivated fetal gene, as a key contributor to right ventricular failure (RVF) progression in pulmonary arterial hypertension (PAH). C_LIO_LISND1 interacts with SERCA2a, promoting its proteasomal degradation, which disrupts sarcoplasmic reticulum calcium reuptake and weakens cardiomyocyte contractility. C_LIO_LICardiomyocyte-specific SND1 deletion restores SERCA2a levels, improves calcium handling, enhances right ventricular function, and increases survival in RVF rats. C_LI What Are the Clinical Implications?O_LIThe reactivation of fetal genes such as SND1 is not just a marker but a pathogenic driver in maladaptive right ventricular remodeling. C_LIO_LITargeting SND1 represents a novel therapeutic approach to improve right ventricular contractility and prevent heart failure progression in patients with PAH. C_LIO_LIThese findings may inform the development of gene- or protein-targeted therapies aimed at stabilizing SERCA2a and preserving right heart function in high-risk populations. C_LI

cell biology↗

bioRxiv2025

Gap-free genomes and transcriptomes uncover race-specific effectors in watermelon wilt pathogen Fusarium oxysporum f. sp. niveum

Watermelon (Citrullus lanatus L.) is one of the worlds most economically important fruit crops, yet it is susceptible to devastating diseases such as vascular wilt caused by Fusarium oxysporum f. sp. niveum (Fon), with limited effective control measures. Fon evolves rapidly in the field to overcome host resistance and global watermelon production is constantly threatened by new pathogenic races. High-quality genomic resources are key to understanding the molecular mechanisms underlying Fon virulence evolution for disease management. Here, we de novo assembled and annotated gapless genomes of three physiological races of Fon (race 1, 2, and 3), and dissected the mechanisms behind their distinctive virulence through comparative genomics and transcriptomics. Whole-genome alignments identified core and accessory chromosomes in Fon where each race carried a unique set of accessory chromosomes or regions. Comparative transcriptomics of Fon infection revealed distinctive temporal patterns of gene expression even among core gene families, particularly those related to cell wall degradation enzymes. Effectoromic prediction and comparative analysis in three gap-free genomes identified 13 race-specific effectors (RSEs) in FonR3, one (FonRSE1) of which was a critical virulence factor of FonR3 on watermelon as demonstrated via functional experiments. The gap-free genome assemblies and annotations, and the RSEs are valuable resources for studying Fon pathobiology and genome evolution, adding in the design of improved disease control strategies.

genomics↗

bioRxiv2025

A transcriptional biosensor reveals mechanisms of α-ketoglutarate signaling to chromatin

Alpha-ketoglutarate (KG) is required for chromatin demethylation but mechanisms controlling KG abundance in the nucleus are poorly defined. Therefore, we designed a biosensor system to monitor this metabolite pool in human cells using an KG-responsive cyanobacterial transcription factor, NtcA. We then coupled this system with a genetic screen to identify genes that regulate KG in the nucleus, defining an inter-organelle pathway in which sequential mitochondrial activities of the GPT2 transaminase and SLC25A11 transporter supply nuclear KG. Using a mouse model of GPT2 deficiency, a human inborn error of metabolism, we found that this pathway controls chromatin methylation in the developing brain. Our work provides a tool to assess KG signaling to chromatin and a framework for leveraging forward genetics to study nuclear metabolite pools.

synthetic biology↗

bioRxiv2025

AAV-mediated ARSA replacement for the treatment of Metachromatic Leukodystrophy

Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative disorder caused by mutations in the arylsulfatase A (ARSA) gene, resulting in lower sulfatase activity and the toxic accumulation of sulfatides in the central and peripheral nervous system. Children account for 70% of cases and become progressively disabled with death occurring within 10 years of disease onset. Gene therapy approaches to restore ARSA expression via adeno-associated viral vectors (AAV) have been promising but hampered by limited brain biodistribution. We report the development of a novel capsid AAV.GMU01, demonstrating superior biodistribution and transgene expression in the central nervous system of non-human primates (NHPs). Next, we show that AAV.GMU01-ARSA treated MLD mice exhibit persistent, normal levels of sulfatase activity and a concomitant reduction in toxic sulfatides. Treated mice also show a reduction in MLD-associated pathology and auditory dysfunction. Lastly, we demonstrate that treatment with AAV.GMU01-ARSA in NHPs is well-tolerated and results in potentially therapeutic ARSA expression in the brain. In summary, we propose AAV.GMU01-ARSA mediated gene replacement as a clinically viable approach to achieve broad and therapeutic levels of ARSA.

neuroscience↗

bioRxiv2025

RNA Architecture Underlies Discontinuous Transcription and Evolution of Coronavirus

Coronaviruses employ discontinuous transcription to produce canonical subgenomic RNAs (sgRNAs) essential for gene expression, as well as non-canonical sgRNAs with unclear function. Nevertheless, the mechanisms regulating the balance between canonical and non-canonical sgRNAs throughout the viral replication cycle remain unknown. We conducted an integrated analysis on 234 transcriptome and 12 RNA-RNA interactome samples across various coronavirus genera. RNA-RNA interactions were identified between TRS-B and TRS-L flanking regions in the same genomic direction, correlating with the formation of canonical junctions. Non-canonical junctions frequently span short or long genomic distance, with short-range junctions generally mediated by reverse complementary stem-loops and coinciding with genomic deletion regions. Conserved long-range non-canonical sgRNAs were identified across different coronaviruses, and these sgRNAs harbor ORF10 or an evolving gene to suppress antiviral innate immune responses. This work establishes a structural framework that enables an understanding of the regulatory mechanism behind discontinuous transcription and the evolutionary pathway of coronaviruses. TeaserDeciphering coronavirus transcription and evolution: an integration analysis of transcriptome and RNA-RNA interactome. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=165 HEIGHT=200 SRC="FIGDIR/small/642953v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1c58502org.highwire.dtl.DTLVardef@9f87d7org.highwire.dtl.DTLVardef@18f3492org.highwire.dtl.DTLVardef@c49362_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

MSMCE: A Novel Representation Module for Classification of Raw Mass Spectrometry Data

Mass spectrometry (MS) analysis plays a crucial role in the biomedical field; however, the high dimensionality and complexity of MS data pose significant challenges for feature extraction and classification. Deep learning has become a dominant approach in data analysis, and while some deep learning methods have achieved progress in MS classification, their feature representation capabilities remain limited. Most existing methods rely on single-channel representations, which struggle to effectively capture the structural information within MS data. To address these limitations, we propose a Multi-Channel Embedding Representation Module (MSMCE), which focuses on modeling inter-channel dependencies to generate multi-channel representations of raw MS data. Additionally, we introduce a "residual" connection along the channel dimension, significantly enhancing the classification performance of subsequent models. Experimental results on four public datasets demonstrate that the proposed MSMCE module not only achieves substantial improvements in classification performance but also reduces computational resource consumption and enhances training efficiency, highlighting its effectiveness and generalizability in raw MS data classification.

bioengineering↗

bioRxiv2025

Emergence of isochorismate-based salicylic acid biosynthesis within Brassicales

Salicylic acid (SA) is a major defense phytohormone. In Arabidopsis thaliana, the isochorismate (IC) pathway is the primary route for pathogen-induced SA biosynthesis. First, the IC synthase (ICS) catalyzes the isomerization of chorismate to IC in chloroplasts. Second, the chloroplast-localized MATE transporter EDS5 appears to transport IC from chloroplasts to the cytosol. Cytosolic IC is then further converted to SA via the GH3 amino acid-conjugating enzyme PBS3. While this pathway is genetically well-characterized in A. thaliana, its evolutionary origin and conservation remain controversial. In this study, through comprehensive phylogenetic, structural, and functional analyses, we demonstrate that the IC pathway emerged within the Brassicales order in a time span between the divergence of Carica papaya and Capparis spinosa. The evolution of the IC pathway was driven by three key adaptations during the time span: (1) enhancement of ICS activity, (2) neofunctionalization of EDS5 after duplication of its ancestral gene, and (3) evolution of a PBS3, whose activity is specialized for glutamate-conjugation to IC. Structural modeling and functional assays reveal that an enhanced salt bridge network in ICS enhanced its activity. One of the duplicated genes, EDS5, acquired key amino acid substitutions in the C-lobe, which likely contributed to the EDS5 neofunctionalization. In addition, the functional PBS3 clade, including A. thaliana PBS3, is restricted to a Brassicales clade. Taken together, this study addresses the evolutionary trajectory of IC-based SA biosynthesis.

plant biology↗

bioRxiv2025

Endometrial microbiome in mares with and without clinical endometritis

Chronic endometritis (CE) has been recognized as an important disease in the clinical theriogenology practice. Studies have suggested that CE is one of the major causes of infertility in breeding mares. However, a comprehensive analysis of the CE microbiome is currently insufficient in published reports. In this paper, we compared the uterine microbiomes of mares with CE to those of healthy mares and propose that there are significant differences in the composition of the uterine microbiome between these two groups of mares. This study suggests that changes in the uterine microbiome may play a vital role in the development and progression of CE in mares, adds to the understanding of the role of the uterine microbiome in CE and in developing targeted treatment strategies.

microbiology↗

bioRxiv2025

Unprecedented Microviridae phages isolated from equine uteri

Descriptions of the virome has only recently returned to the fore. There is much information yet to be discovered. Single-stranded DNA (ssDNA) viruses as an exceptionally widespread virus can infect diverse hosts. The simple genome of ssDNA viruses leads to a high propensity for mutation and recombination, which often pose infectious threats to society. However, research investigating ssDNA phage genomes have ignored the reproductive tract communities. Here we have identified novel members of the Microviridae family from horse (Equus cabalas) uteri, with completed genomic sequences. Comparative and phylogenetic analyses between different animals indicate that genetically similar animals to the equine likely have the same or similar viruses in their uterine microbiome. This research not only expands the understanding of the diversity within Microviridae family, but also provides new insights into potential therapeutics for uterine infectious disease.

microbiology↗

bioRxiv2025

Mammalian Uteri Contain a Diverse Virome: Insights from Healthy Mares

The Earths estimated 1031 virions, primarily phages, significantly impact microbial ecosystems. Despite their abundance, viromes remain relatively understudied. This is especially the case in domestic animals. Although recent studies have described the presence of a dynamic commensal microbiome in mammalian uteri, no studies have attempted to characterize the commensal virome in a mammalian uterus. In this study we have established for the first time the presence of a sparse, but diverse native virome in the equine uterus. The resulting virome database consists of 513 non-redundant viral genomes (>2 kb). Taxonomic annotations revealed a diverse virome dominated by Gammaretrovirus, Mamastrovirus, Sapovirus and Rosenblumvirus. Notably, 75% of the assembled genomes represented novel species. The phylogenetic tree unveiled distinct clades suggesting unexplored viral diversity with the uterine environment. Furthermore, bacterial hosts for equine uterine phages were predicted, aligning with previous studies findings. Most notably, the study identified antibiotic resistance genes within the virome, hinting at potential gene transfer mechanisms between bacteria and viruses. This study establishes the first uterine virome of any mammal, shedding light on a previously unexplored domain. The findings highlight the potential for phage therapy in reproductive infectious diseases and the importance of understanding the maternal gestational environment. Moreover, the study underscores the need for further studies to expand the uterine viromes, paving the way to deeper understanding of uterine microbiome and its implications for animal and human health.

microbiology↗