Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes substantial morbidity in swine and may pose a zoonotic risk because of its cross-species transmission potential. Type I interferon (IFN-I) signaling is central to antiviral defense, initiated through the mitochondrial antiviral signaling (MAVS)-TBK1-IFN regulatory factor 3 (IRF3) axis and executed by the downstream JAK-STAT1-STAT2-IRF9 (ISGF3) pathway; however, how PDCoV circumvents both the induction and effector arms of this cascade remains incompletely understood. Here, we identify PDCoV nonstructural protein 13 (Nsp13) as a potent antagonist of IFN-I responses. Ectopic expression of Nsp13 markedly reduces IFN-β production and the expression of IFN-stimulated genes (ISGs, such as ISG56 and CXCL10). Mechanistically, Nsp13 directly binds the C-terminal domain (CTD) of TBK1 and competitively disrupts TBK1 interactions with IRF3 and MAVS. In addition, Nsp13 preferentially binds IRF9 and impairs its nuclear translocation, thereby inhibiting IFN-α-induced signaling. Notably, PDCoV Nsp13 exhibits a host-target binding profile similar to that of SARS-CoV-2 Nsp13, yet it does not alter TBK1 ubiquitination or protein stability. Collectively, these findings reveal a dual-layer immune evasion strategy whereby PDCoV Nsp13 suppresses both IFN induction and downstream signaling, and highlighting Nsp13 as a potential target for antiviral intervention.

While systemic immune dysregulation is well-documented in HIV infection, its impact on blood and respiratory tract viromes remains poorly understood. This study characterizes HIV-associated alterations in viral communities and examines their clinical relevance. Using viral metagenomics, we compare 203 ART-treated HIV-positive individuals and 120 healthy controls. HIV infection significantly restructures the blood virome, shifting from bacteriophage dominance (96.2% in controls) to eukaryotic virus predominance (69.1%). Increased alpha diversity, significant β-diversity divergence, and heightened dispersion heterogeneity are observed in HIV cases. Consistent enrichment of Flaviviridae, Parvoviridae, and Anelloviridae is detected. Throat viromes maintain phage dominance (>90%) but exhibit strain-level diversification, including Microviridae proliferation. Network analysis reveals Retroviridae-Anelloviridae co-dynamics (r = +0.562) and identifies Picobirnaviridae as a key interactor. Functional analysis shows enriched viral replication and host modulation genes. Compartment-specific disruption patterns nominate Pegivirus C, parvovirus B19, and Anelloviruses as potential biomarkers. Cross-kingdom viral interactions suggest novel mechanisms influencing disease progression and support future virome-targeting adjunct therapies.

The interaction between parasitic infection and the host virome represents a frontier issue in microbial ecology, yet how Echinococcus infection affects the multi-organ virome and whether these alterations hold diagnostic or interventional potential remains poorly understood. In this study, we performed viral metagenomic sequencing on gut, liver, and lung samples from both infected and uninfected mice, integrating community structure clustering, diversity indices, and differential analyses, including STAMP and LEfSe. Our results reveal that Echinococcus infection induced significant tissue-specific virome remodeling. Compared to healthy controls, gut virome diversity increased, characterized by marked expansion of the class Caudoviricetes, particularly the family Siphoviridae (LDA > 4), alongside Picornaviridae enrichment (LDA > 4). In contrast, virome diversity decreased in both the liver and lung, with significant enrichment of Reoviridae (LDA > 4) in the liver and Retroviridae (LDA > 4) in the lung, respectively. Conversely, Picobirnaviridae (LDA > 4) was significantly reduced in the infected liver and lung. Based on phylogenetic analysis, Echinococcus infection significantly altered the murine gut viral community, with eukaryotic viruses (e.g., norovirus, picobirnavirus, and picornavirus) detected exclusively in infected animals, while bacteriophage populations remained stable across groups. Phage host prediction further revealed that phages enriched in infected samples targeted opportunistic pathogens (Clostridium septicum, Trueperella pyogenes), whereas control phages predominantly targeted commensals (Bacteroides thetaiotaomicron). Together, these findings demonstrate that Echinococcus infection drives both eukaryotic virus enrichment and a shift in phage predation toward pathogens, suggesting that infection-induced immune modulation creates a permissive environment for viral replication and associated bacterial dysbiosis.

Gastric cancer (GC) is a prevalent malignancy worldwide, yet effective early diagnostic tools remain lacking, and the role of the virome, a key component of the tumor microenvironment, in GC progression is largely unknown. This study aimed to characterize the virome landscapes in peripheral blood and feces of GC patients versus healthy controls, and to identify viral signatures associated with GC onset and metastasis. We performed viral metagenomic sequencing on pooled libraries from 100 GC patients (45 non-metastatic, 55 metastatic) and 50 healthy controls, followed by taxonomic annotation, diversity assessment, LEfSe differential abundance testing, and co-occurrence network analysis. In blood, the GC virome shifted from a bacteriophage-dominated profile in controls to one overwhelmingly dominated by Anelloviridae (> 80%), with significantly decreased alpha diversity. In contrast, the gut virome of GC patients showed increased alpha diversity and coexistence of diverse bacteriophages. LEfSe identified betatorquevirus in blood as a key discriminatory taxon for GC. Network analysis revealed negative correlations between Anelloviridae and multiple bacteriophage families, suggesting niche competition. We also discovered 67 provisional novel anellovirus species and one novel gemykibivirus in GC patient blood. Collectively, our findings indicate that GC is associated with compartment-specific virome remodeling in blood and gut, and that expansion of blood anelloviruses holds promise as a non-invasive biomarker. This study provides a foundational resource for understanding the virome's role in GC.

As the most abundant subset of leukocytes in the innate immune system, neutrophils are central to host defense, particularly against bacterial and fungal infections. With advances in tumor microenvironment (TME) research, their multifunctional roles in tumor biology have been clarified, and the identification of neutrophil extracellular traps (NETs) has provided a novel perspective for understanding neutrophil-mediated regulation of tumor initiation, progression, and metastasis. NETs are reticular structures of chromatin fibers released by activated neutrophils, comprising DNA backbones, histones, and various antimicrobial proteins, initially recognized as an antibacterial defense mechanism. However, recent studies reveal NETs exert a dual role in tumor progression: directly promoting metastasis by enhancing tumor cell migration, trapping circulating tumor cells (CTCs), reactivating dormant cancer cells, and increasing vascular permeability, while also reshaping the TME to support pre-metastatic niche formation. This review systematically summarizes the molecular mechanisms of NETs in gastrointestinal tumor initiation, progression, and metastasis, and explores potential NETs-targeted anti-tumor therapeutic strategies, aiming to provide a theoretical basis for novel gastrointestinal tumor treatment directions.

The Himalayan marmot (Marmota himalayana) is a keystone species in the Tibetan Plateau ecosystem and serves as a potential reservoir host for multiple zoonotic pathogens. To characterize its hepatic virome, this study conducted a systematic analysis of 70 marmot liver samples collected from the Three-River-Source Region in Qinghai Province using viral metagenomics. We identified more than 60 viral species belonging to 13 families. The species accumulation curve indicated that the sequencing effort captured the majority of the viral diversity present. Community analysis revealed that the family Retroviridae was the dominant viral group across all samples, though significant heterogeneity was observed among geographically distinct populations. Specifically, the relative abundance of Anelloviridae was markedly higher in the Chengduo group, whereas Parvoviridae exhibited exceptionally high library-specific enrichment in specific libraries. Furthermore, the study successfully assembled complete or near-complete genomic sequences of multiple strains belonging to the families Polyomaviridae, Anelloviridae, and Parvoviridae. Phylogenetic analysis demonstrated that these newly identified viral strains were most closely related to known marmot-origin viruses, clustering within distinct, host-specific evolutionary clades. This clustering pattern indicating host-associated of the viruses with their marmot hosts. Previous virome studies in marmots have primarily focused on the gut, peripheral blood, and other extrahepatic tissues, with no systematic viral metagenomic profiling of the liver in this species to date. The findings offer crucial scientific insights for the early warning and control of wildlife-origin diseases on the Tibetan Plateau.

Tripartite motif-containing protein 21 (TRIM21/Ro52) is a pivotal E3 ubiquitin ligase and cytoplasmic fragment crystallizable receptor (FcR). It plays a crucial role in viral infections, autoimmune disorders, and cancers by regulating multiple cell signaling axes, including the NF-κB, RIG-I-like receptor (RLR), cGAS-STING, and Toll-like receptor (TLR) pathways. Type I interferon (IFN-I), a pleiotropic cytokine, is produced via these immune signaling pathways, which are often triggered by viral components. TRIM21 both activates IFN-I signaling and mediates its negative feedback through post-translational modification of key immune signaling proteins, thereby maintaining immune homeostasis. In recent years, TRIM21 has been found to dually regulate autophagy and IFN-I in the context of virus–host interplay. Herein, we systematically summarize the functional roles of TRIM21 in virus-triggered intracellular immunity, aiming to provide insights for researchers and inspire further investigation in this area.

Papillomavirus (PV), a transmissible oncogenic pathogen, has recently been identified in both healthy and diseased giant pandas, posing a critical threat to this endangered species and highlighting the need for sensitive diagnostics. Here, we present an accumulation-mode organic photoelectrochemical transistor (OPECT) immunosensor for the sensitive detection of giant panda PV. We cloned and expressed the codon-optimized E6 protein gene of giant panda PV to generate polyclonal antibodies. The sensor employs a crystalline C4N photogate containing pyridinic nitrogen and graphitic nitrogen with a narrow bandgap (1.27 eV), broad ultraviolet-visible absorption, and high gating effect (a current gain of 10,000) for efficient charge separation and migration. This OPECT immunosensor achieves a detection limit of 40 fg mL-1, a broad dynamic range from 0.1 pg mL-1 to 161 ng mL-1, and high specificity. It enables accurate analysis of giant panda clinical samples, offering a robust tool for PV surveillance in this vulnerable species.

The giant panda (Ailuropoda melanoleuca) is a flagship species for biodiversity conservation, yet the viral communities inhabiting its upper respiratory tract (URT) remain poorly characterized. In this study, we performed viral metagenomic sequencing on 13 pooled libraries derived from 130 nasopharyngeal swabs collected from giant pandas between 2018 and 2021. The assembly yielded 16 complete or near-complete viral genomes, predominantly of DNA viruses belonging to the families Papillomaviridae, Genomoviridae, and Parvoviridae. Notably, we identified the complete genome of a novel Parvoviridae species within the subfamily Densovirinae. Phylogenetic analysis revealed that this virus clusters with invertebrate-infecting viruses, suggesting that it likely represents an arthropod-associated viral element derived from respiratory parasites rather than a direct vertebrate pathogen. Although the alpha diversity remained stable, beta diversity analysis revealed significant temporal shifts in viral community composition (P = 0.02). This study provides the first systematic characterization of the giant panda URT virome, establishing a critical baseline for disease surveillance and highlighting the complex interplay between the host and its environment-associated viral elements.

RNA viruses, a widely distributed group of pathogens in nature, possess exceptionally high genetic diversity and rapid evolutionary potential. High-altitude ecosystems, represented by the Qinghai-Tibet Plateau, with their unique environmental conditions, may harbor distinct viral communities. However, there remains a lack of systematic understanding regarding the composition and distribution of RNA viruses in wildlife under such extreme environments. In this study, a total of 741 fecal samples were collected from three regions on the Qinghai-Tibet Plateau, and viral metagenomics technology was used to reveal the composition and diversity of RNA viruses in the fecal samples of six species of herbivorous wild animals on the plateau. We identified a substantial abundance of RNA viruses, classified into 18 distinct viral families. Furthermore, the structure of the viral communities varied among different host species. Through assembly, 28 viral sequences belonging to the families Astroviridae, Picornaviridae, Picobirnaviridae, Tobaniviridae, and Caliciviridae were identified. Phylogenetic analysis revealed that the newly identified viral strains share close relationships with viruses found in humans, marmots, and other mammals. The results indicate that wildlife in this region are reservoirs of unidentified RNA viruses, some of which may pose potential threats to public health and the animal husbandry. These findings provide crucial scientific evidence and data support for future virus surveillance, ecological risk assessment, and the prevention and control of emerging infectious diseases at their source.

Amniotic fluid is a critical compartment in pregnancy; however, its virome remains poorly characterized, and potential associations with maternal–fetal health are largely unexplored. This study aimed to comprehensively profile the human amniotic fluid virome and explore its association with maternal health status during pregnancy. We performed viral metagenomic sequencing of 515 amniotic fluid samples from 515 pregnant women in Changzhou, China, including healthy pregnancies (n = 275) and pregnancies with complications (n = 240). Viral sequences were identified using a bioinformatics pipeline, and phylogenetic analyses were used to assess genetic relationships. We identified diverse viral sequences, including members of viral families such as Anelloviridae and Paramyxoviridae. BLAST-based nucleotide comparisons showed high nucleotide identity to previously reported viruses, indicating that many detected sequences are closely related to known viruses. Phylogenetic analyses further supported their placement within established viral taxa. Community-level analyses indicated differences in virome composition profiles between the healthy control and disease groups. Our findings describe a previously undercharacterized virome in human amniotic fluid. This study establishes a basis for future investigations into the origins and potential associations of these viral signatures with pregnancy health, highlighting the importance of assessing their clinical relevance for both maternal and neonatal outcomes. Because metagenomic sequencing detects viral nucleic acids, these findings do not establish viral infectivity or causality.

Penguins, as distinctive marine birds, play important roles in polar and sub-Antarctic ecosystems, yet the diversity and species-specific distribution of their gut viromes remain insufficiently understood. Here, we used viral metagenomics to characterize the cloacal viromes of four penguin species-Spheniscus humboldti (S. humboldti), Pygoscelis papua (P. papua), Pygoscelis adeliae (P. adeliae), and Aptenodytes forsteri (A. forsteri)-collected at Chimelong Ocean Kingdom. A total of 219 viral sequences representing potentially novel lineages were identified, with more than 94% sharing <80% amino acid similarity with previously known viruses. These sequences were assigned to several viral families, including Parvoviridae, Caliciviridae, Anelloviridae, Circoviridae, and Microviridae, among others. Marked interspecies differences in virome composition were observed: Parvoviridae dominated in S. humboldti, Microviridae were enriched in P. papua, Caliciviridae accounted for a substantial proportion in A. forsteri, and P. adeliae displayed the greatest overall virome diversity. Multiple-virus co-detections, particularly involving Parvoviridae, were frequent in S. humboldti. Phylogenetic analyses showed that many penguin-associated viruses clustered with viruses infecting other avian and fish hosts, suggesting possible dietary or environmental origins of some detected viral sequences. These findings expand current knowledge of penguin gut virome diversity and host-associated differences and provide a valuable foundation for evaluating the ecological roles, health implications, and transmission risks of penguin-associated viruses.IMPORTANCEThis study uncovers significant diversity in the gut viromes of four penguin species, revealing over 219 viral sequences representing potentially novel lineages, many of which showed host-associated distribution patterns. Using viral metagenomics, we identified notable interspecies differences, with Parvoviridae predominating in Spheniscus humboldti and Microviridae being enriched in Pygoscelis papua. These findings highlight the complexity of viral community structures in penguins, including frequent viral co-detections, which could impact host health and ecological adaptation. Additionally, novel bacteriophage communities were identified, emphasizing their potential role in shaping the gut microbiome and influencing viral dynamics. This work provides new insights into viral diversity in wildlife and lays the groundwork for future studies on viral transmission risks and ecological conservation.

ABSTRACT Getah virus (GETV) is an emerging mosquito-borne alphavirus that poses a growing threat to animal and public health. However, the molecular mechanisms underlying its pathogenesis and immune evasion remain poorly defined. This study demonstrated that GETV infection suppressed the activation of interferon β (IFN-β) or IFN-stimulated response element after poly(I:C) stimulation. By screening nine viral proteins (non-structural proteins 1–4 [nsP1–4] and C-E3-E2-6K-E1), we discovered that the nsP2 protein of GETV could effectively inhibit the production of IFN-β and IFN-stimulated genes. Subsequently, we discovered that nsP2 disrupted the retinoic acid-inducible gene I-like receptor signaling pathway by causing widespread cellular shutoff and directly targeting inhibitor of kappa-B kinase ε (IKKε). Mechanistically, the inhibitory function of nsP2 is contingent upon the protein’s structural integrity and the presence of proline 717 and nuclear localization signal-related residues. Additionally, we illustrated that nsP2 markedly inhibited TRAF2-induced K63-linked polyubiquitination and phosphorylation of IKKε, which is essential for activating IKKε. Altogether, the present study elucidated a new mechanism in which GETV modulates the host’s antiviral immunity.IMPORTANCEGetah virus (GETV), a multi-host alphavirus of the Togaviridae family, imposes a significant economic burden on the swine industry by causing fever, diarrhea, reproductive disorders in sows, and elevated mortality in newborn piglets. Here, we reveal that GETV non-structural protein 2 antagonizes interferon β (IFN-β) production through a dual mechanism: it induces broad cellular shutoff and directly interacts with inhibitor of kappa-B kinase ε (IKKε) to prevent its activation. This strategy effectively disrupts type I IFN responses by suppressing antiviral gene expression, such as IKKε, IFN-I, and IFN-stimulated genes, and impairing retinoic acid-inducible gene I-like receptor signaling activation. Our findings not only uncover a novel mechanism of GETV immune evasion but also establish the rationale for novel therapeutic targets, suggesting a new avenue for the treatment and intervention of GETV infection.

Aedes albopictus is a globally important mosquito species capable of transmitting a variety of viruses. In this study, a total of 440 Ae. albopictus individuals were collected from Fanchang, Anhui Province, and 22 tissue libraries were constructed for metagenomic sequencing. A total of 649,930,614 reads were obtained and assembled into 209,335 contigs, of which 18,339 showed similarity to known viral proteins, spanning 13 viral families including both DNA and RNA viruses. Because several DNA virus-related sequences were recovered from the dataset, we further focussed on CRESS-DNA virus-related sequences and members of the family Parvoviridae. Phylogenetic analysis showed that three CRESS-DNA virus-related sequences clustered within Smacoviridae and Genomoviridae, while two Parvoviridae genomes were assigned to Brevihamaparvovirus and Protoparvovirus. These findings provide a metagenomic overview of the Ae. albopictus-associated virome in Anhui Province and provide baseline information on mosquito-associated DNA virus-related sequences in this region.

Endogenous retroviruses (ERVs) are a dynamic and biologically significant component of vertebrate genomes, with integration events spanning deep evolutionary time. The crab-eating macaque (Macaca fascicularis) is an important non-human primate model for biomedical research because of its close phylogenetic relationship to humans and its conservation status as an endangered species. However, the ERV complement of its genome has not been systematically characterized. Using the current highest-quality chromosome-level genome assembly for this species, we performed a genome-wide, homology-based survey of relatively intact ERV proviruses in M. fascicularis. We identified 106 proviral loci distributed across all chromosomes. Phylogenetic reconstruction based on conserved reverse transcriptase domains classified these elements into β-, γ-, and unclassified lineages, with β- and γ-retroviral lineages predominating. LTR divergence-based dating indicated that these proviruses represent multiple waves of historical retroviral activity and span a broad range of integration ages. This curated dataset provides a high-confidence reference set for investigating the evolutionary history and genomic impact of preserved ERV proviruses in an endangered primate model; however, it does not include degraded ERV fragments or solo LTRs.

Respiratory tract infections represent a leading cause of morbidity and mortality globally, with viral pathogens accounting for a substantial proportion of these cases. However, research on the human respiratory virome is still in its infancy, and our understanding of this field remains relatively limited. In the present study, viral metagenomic sequencing was conducted on 65 sputum samples obtained from patients with severe fungal infections. We successfully assembled viral genome sequences belonging to four distinct viral families: Anelloviridae, Genomoviridae, Microviridae, and Inoviridae. Through systematic analysis of the virome composition, this study characterized the structural features of the respiratory virome in patients with severe fungal infections. The findings provide a foundational description of viral diversity in this specific clinical context. These findings lay a theoretical foundation for clinical pathogen detection, targeted interventions, and the development of future prevention strategies.

Most human pathogens, while originating from animals, have crossed species barriers to infect humans, often leading to outbreaks of new infectious diseases. Despite significant efforts, the mechanisms, timing, and locations of these emerging diseases remain largely uncertain. Here, using a viral metagenomic approach, we discovered a novel canine-associated parvovirus in human oropharyngeal secretions. Molecular screening revealed the presence of this parvovirus in different canine tissues, including 24 of 108 pharyngeal lymph node samples. Further molecular investigation showed that the virus was detected in the oropharyngeal secretions of pet dogs and in human samples that were not linked to these animals. This parvovirus was therefore named human-canine associated parvovirus 1 (HCAPV-1). Nine complete genomes of HCAPV-1 were acquired through next-generation sequencing, combining Sanger sequencing. Genomic and phylogenetic analyses indicate that these nine strains of HCAPV-1 belong to the genus Protoparvovirus and form a distinct clade, with their closest relatives being newlaviruses from foxes. Amino acid substitutions have been characterized in the capsid proteins of the variants of HCAPV-1, which potentially alter their infection patterns. Potential genomic recombination was also observed in HCAPV-1. Taken together, our findings reveal the presence of a novel parvovirus in both canine and human samples, highlighting the need to investigate its host range and transmission dynamics.IMPORTANCEThis study identified a novel parvovirus, human-canine associated parvovirus 1 (HCAPV-1), which was detected in human oropharyngeal secretions and various canine tissues, suggesting that its host range may extend beyond a single species. Phylogenetic analysis revealed that HCAPV-1 forms a distinct clade within the genus Protoparvovirus, closely related to newlaviruses from foxes. Amino acid substitutions observed in the capsid proteins of HCAPV-1 variants indicate genetic divergence, warranting further investigation into their potential implications for host interactions. Recombination events may have contributed to its emergence. This finding highlights the importance of continued surveillance in settings where humans and companion animals coexist and underscores the need for further research to clarify the ecological and host-range characteristics of such viruses.

IntroductionThis study aimed to characterize the viral diversity in the blood of marmots in the Qinghai-Tibet Plateau region, to assess their role as potential viral reservoirs and evaluate the potential implications for wildlife and human health.MethodologySeventy marmot blood samples were collected from Yushu and Guoluo Prefectures in Qinghai Province. Viral communities were comprehensively analyzed using high-throughput sequencing and bioinformatics techniques.ResultsAnalysis identified a wide range of viral families, including Anelloviridae, Flaviviridae, Parvoviridae, and Polyomaviridae, and revealed multiple novel viral sequences. Notably, we documented the first evidence of Anelloviridae in marmot serum; phylogenetic analysis indicated these sequences cluster with those from marmot feces and tissues, suggesting a natural host relationship. A critical finding was the detection of Tick-borne encephalitis virus, with a sequence highly similar to human-derived strains, implying potential involvement of marmots in the transmission cycle. Furthermore, identification of a novel polyomavirus was supported by prediction of all main large tumor antigen functional domains and motifs, including a putative nuclear localization signal between its LXCXE motif and origin-binding domain, typical of mammalian-infecting polyomaviruses. Comparative analysis revealed significant regional differences in viral diversity between sampling areas, potentially linked to local ecological factors.DiscussionThis study significantly expands the known viral diversity in marmots and underscores their role as potential zoonotic reservoirs. However, the functional and pathogenic implications of these viruses require further experimental validation. These findings highlight the importance of ongoing wildlife surveillance for understanding viral ecology and mitigating emerging public health risks.

Endogenous viral elements serve as molecular fossils of ancient viral infections, providing valuable evidence for reconstructing the evolutionary history of modern viruses and their hosts. These genomic remnants also provide crucial benchmarks for calibrating viral evolutionary timelines. Here, our flanking sequence analysis reveals that densovirus NS1 sequences are chromosomally integrated in Platyhelminth genomes. Furthermore, their evolutionary dynamics reflect an ancient host-virus codivergence event dating to the Ediacaran-Cambrian transition (approximately 692 million years ago, MYA). Phylogenomic analyses delineate profound divergence between endogenous densovirus sequences in Platyhelminthes and exogenous Parvoviridae sequences, with distinct phylogenetic clustering supporting long-term endogenization. Structural alignments reveal significant global divergence (RMSD: 15.048-36.725 Å) yet striking local conservation in NS1 proteins, with the ATPase (RMSD: 0.271-1.756 Å) and effector domains (RMSD: 2.446-4.775 Å) remaining highly conserved across Platyhelminth hosts. The timescale phylogenetic tree inferred ancient divergence times of 233.51 MYA for Schistosoma-Dicrocoelium and 190.43 MYA for the Clonorchis sinensis, Opisthorchis viverrini, and Paragonimus westermani lineage. Distance matrix analysis revealed pronounced interspecific divergence and intraspecific conservation in NS1 sequences, consistent with a host-virus codivergence model. These findings reveal the preservation of replication-critical domains and the optimization of host-specific adaptation, providing molecular evidence for virus-parasite coevolution over geological timescales. Collectively, our findings reshape our understanding of virus-host coevolution and offer a framework to reconstruct paleoviral dynamics using endogenous "molecular fossils."IMPORTANCEThis study provides evidence of densoviral endogenization in Platyhelminth hosts, advancing understanding of virus-host codivergence and offering a framework for reconstructing paleoviral dynamics using endogenous "molecular fossils."