Search Results (338)

Rodents and shrews are important reservoir hosts due to their close association with human activities and their role in carrying various zoonotic pathogens. Recently, meta-transcriptomic sequencing has become a powerful tool for surveilling and screening novel pathogens from wild animals. However, many of these studies focused only on the diversity and genetic evolution of viruses from wildlife, while ignoring non-viral pathogens such as bacterial and eukaryotic microorganisms. Here, we performed a comprehensive infectome analysis of 227 tissue samples collected from 42 rodents and 16 shrews across six cities of Guangdong Province, China. We identified 34 viral families, including 23 mammalian viruses. Phylogenetic analysis revealed a henipavirus from the kidneys of shrews closely related to the Langya virus with potential infection risks to humans. Additionally, two potential pathogenic bacteria and 12 eukaryotic pathogens from six genera were found, showing clearer organ tropism than viruses. Interestingly, a moderate positive abundance correlation between Usmuvirus newyorkense and Trichinella suggested a potential virus–parasite association. We used machine learning models to evaluate the zoonotic potential of the obtained viruses, which indicated that 15 of 23 viral species were high risk for human infection. These findings provide important insight into the substantial zoonotic threat posed by pathogens circulating in wild small mammals in southern China and highlight the necessity for persistent wildlife pathogen surveillance. Full article

The rectal mucosa houses a large number of viruses with important roles in shaping the local microbial communities and modulating immune responses, which could influence host susceptibility to infection and other diseases. Unique composition of the gut microbiome, including the predominance of clinically significant eukaryotic viruses like herpesviruses, cytomegalovirus, and human papillomavirus, has been described in both people with HIV (PWH) and men who have sex with men (MSM) vulnerable to HIV. Despite these insights, the rectal virome and the clinical implications of virome–bacteriome–immune interactions in the rectal mucosa remain poorly understood. In this review, we synthesize existing data on the composition of the rectal virome, its interactions with the bacteriome and the immune system, and implications on clinical outcomes in people living with or vulnerable to HIV. We also highlight the gaps and research needed to further explore and unravel these relationships. Full article

The human virome, comprising eukaryotic viruses, bacteriophages, and viral genetic material, is a dynamic component of the microbiome with growing relevance in infectious diseases. This narrative review is structured to: (i) summarize the general composition of the human virome and methodological challenges, including the fraction of unclassified viral “dark matter”; (ii) describe virome alterations in chronic infections; and (iii) explore site-specific virome dynamics across respiratory, intestinal, and genito-urinary tracts in both chronic and acute infections. In chronic viral infections such as HIV, HBV, HCV, and HPV, a recurrent feature is the expansion of Anelloviridae—particularly torque teno virus—reflecting impaired immune surveillance rather than direct pathogenicity, suggesting their potential as surrogate biomarkers of immune competence. Evidence on virome changes in chronic bacterial and parasitic infections remains limited, highlighting a critical knowledge gap. Acute infections are associated with compartment-specific shifts in eukaryotic viruses and bacteriophage communities, often paralleling changes in bacterial populations and inflammatory responses, with implications for disease severity. Despite advances in metagenomic approaches, a substantial proportion of viral sequences remains unclassified, limiting functional interpretation. Nevertheless, virome profiling provides an ecosystem-level perspective, offering insights beyond single-pathogen detection and supporting emerging applications in diagnostics, immune monitoring, prognosis, and infectious disease surveillance. Full article

Feline calicivirus (FCV) is a major pathogen that threatens feline health worldwide. Its global prevalence, extensive genetic variability, and limited cross-protection among strains present significant challenges for vaccine development. In this study, an infectious clone of the FCV-GDJM202201 strain was constructed using the eukaryotic expression plasmid pcDNA3.1 under the control of the cytomegalovirus (CMV) promoter. The rescued virus, rGDJM-A4822T, exhibited growth kinetics comparable to those of the parental strain in vitro. Subsequently, two recombinant viruses, rGDJM-VP1_JL and rGDJM-VP1_SH, were generated by replacing the VP1 gene in the GDJM202201 backbone with those from heterologous FCV strains. Notably, these recombinant viruses exhibited reduced viral titers compared to rGDJM-A4822T. Finally, neutralization assays revealed differential neutralizing antibody titers among the recombinant FCVs, with rGDJM-A4822T inducing higher neutralizing antibody titers and cross-neutralizing activity. Collectively, this study establishes an FCV infectious clone that can be used to rescue recombinant viruses carrying heterologous VP1 proteins and to evaluate neutralizing antibody responses. Full article

The eukaryotic genome is organized into distinct structural units dictated by architectural proteins. The major host architectural protein CCCTC-binding factor (CTCF) is usurped by DNA viruses to regulate viral gene expression. This review will discuss the major ways large (EBV, HSV, HCMV) and small (HPV, HBV, AAV) DNA viruses mimic eukaryotic genome topology using CTCF to regulate viral gene expression. We will further discuss how changes in genome topology can drive virally induced oncogenic progression. Knowledge gained from studying viral genome folding mechanisms will inform the development of targeted anti-viral agents and inform the modification of viruses to serve as gene therapy vectors. Full article

The eukaryotic translation initiation factor 4E (eIF4E) family plays a dual role in plants, regulating cap-dependent protein synthesis and mediating susceptibility to viruses in the family Potyviridae. In cowpea (Vigna unguiculata (L.) Walp.), an economically important legume cultivated worldwide, the structural determinants of these isoforms remain largely unexplored. This study characterizes the genomic organization, evolutionary history, and conformational dynamics of eIF4E, eIF(iso)4E, and nCBP in cowpea using a multi-omics approach. Genome mining identified three paralogous genes located on chromosomes 4, 6, and 7, showing high synteny with Phaseolus vulgaris. Phylogenetic analysis confirmed nCBP as the ancestral Class I lineage, distinct from the Class II eIF4E and eIF(iso)4E clades. Theoretical models for the isoforms were generated and subsequently validated by molecular dynamics simulations, revealing that while all isoforms preserve the canonical tertiary architecture and an electropositive cap-binding pocket, eIF(iso)4E exhibits superior structural compactness and hydrogen-bond stability. These biophysical features highlight their role as a stable anchor for viral VPg proteins. By elucidating the atomic-level landscape of these factors, we provide a robust structural framework to guide allele mining and genome-editing strategies aiming to engineer virus-resistant cowpea cultivars without compromising agronomic performance. Full article

African swine fever virus (ASFV) causes a fatal disease in domestic pigs and wild boars (Sus scrofa), leading to nearly 100% mortality during acute infection and significant economic losses in swine production. Unlike other eukaryotic viruses, ASFV encodes a histone-like nucleic acid-binding protein, pA104R, which is highly conserved and present in all described ASFV isolates of different genotypes. Moreover, A104R-like sequences have been identified in the genomes of soft ticks, which can replicate and transmit ASFV. Using a virulent genotype IX field isolate from Kenya, we analyzed the importance of A104R for viral replication in a permissive wild boar cell line (WSL). In this study, we confirmed that A104R is not essential for in vitro replication of ASFV. Loss of A104R did not detectably affect viral DNA replication or RNA transcription but led to a moderate reduction in virus titers and plaque sizes. Substitution of A104R with a similar ASFV-like element derived from the genome of an Ornithodoros moubata soft tick was not capable of rescuing the deletion mutant phenotype. In contrast, reintroduction of the authentic A104R open reading frame (ORF) into the deletion mutant fully restored wild-type virus growth properties. In accompanying studies, we verified the DNA-binding activities of the ASFV- and tick-derived A104R proteins and performed mass spectrometric analyses of the pA104R interactome. These experiments revealed, besides DNA-dependent co-precipitated proteins, specific DNA-independent protein–protein interactions of pA104R with other viral and cellular proteins. Full article

Microbial communities on obturator prosthesis biofilms have yet to be investigated. This pilot study explores eukaryotes, prokaryotes, and viruses present on obturator prosthesis biofilms using metagenomics. The prostheses of the selected patients (n = 3) were collected and their biofilms were physically removed. The total genomic DNA was extracted, followed by metagenomic analysis. The microbial diversity in each of the investigated biofilms was exceptionally abundant. Between 2616 to 3024 species were detected in the three biofilms. The highest percentage included prokaryotes and unclassified species, followed by low percentages of fungi, viruses, and archaea. Unusual pathogens rarely reported in oral biofilms, such as Mycobacterium and other species, were also found at very low percentages. Unigenes for functional pathways related to metabolism, cellular processes, human disease, and other microbial unigenes were abundant. In addition, unigenes for several antibiotic-resistance mechanisms were also detected. This study reveals, for the first time, that biofilm formation on obturator prostheses comprises a variety of dynamic microbial communities, suggesting a putative role in health and disease in patients following maxillofacial surgery. Full article

Over the past two decades, it has become clear that gene expression in eukaryotic cells is regulated by diverse RNA molecules. In this process, new RNAs have been discovered, and the roles of their modified molecules have been progressively elucidated. In this review, we first describe how RNA and its modifications function in virus-infected cells. We use adenovirus and several other viruses as models during the early stages of infection, which we believe determines the fate of infected cells. Next, we reviewed the process of identifying the early mRNA transcription initiation sites in adenovirus-infected cells. The results showed that the transcription initiation sites for the E1 and E4 mRNAs—known as adenovirus oncogenes—are highly complex. The same level of complexity in transcription initiation sites has been suggested for oncogenes in several other DNA tumor viruses, including SV40, polyomavirus, and papillomavirus. It is now understood that the transcription of the early adenovirus mRNA involves alternative splicing, rather than constitutive splicing, as we previously demonstrated. Furthermore, recent research indicates that the abnormal alternative splicing of intracellular mRNA may induce cellular carcinogenesis. Finally, we discuss whether alternative splicing plays a role in the carcinogenic effects of DNA tumor viruses, such as adenovirus. Additionally, we discuss that alternative splicing plays a crucial role in adenovirus replication. Full article

Riverine ecosystems represent critical nodes in the global carbon cycle, where the mechanistic role of viruses in modulating eukaryotic carbon cycling remains underexplored, particularly across heterogeneous landscapes. Here, we applied metatranscriptomics to dissect how multi-scale environmental factors and viral gene activity jointly regulate the spatial transcription of carbon cycling genes in riverine eukaryotic communities along the Yongding River, China. Our analyses reveal pronounced spatial heterogeneity in both viral gene expression—notably major capsid proteins of large eukaryotic DNA viruses—and carbon fixation, conversion, and metabolism pathways, peaking in agriculturally impacted plain regions. Multivariate statistics and network analyses demonstrate that land use enhances viral gene activity, serving as biological amplifiers that modulate host carbon metabolism and transformation. Structural equation modeling further identifies a cascade in which cropland coverage elevates viral gene expression, ultimately driving a 1.8-fold increase in TCA cycle gene transcription in plain regions, whereas nitrogen loading at the site scale suppresses viral activity and carbon fixation. Phylogenetic analysis corroborates that virus–host specificity underpins these spatial patterns. Collectively, these findings advance a new model in which viruses act as key intermediaries, transmitting multiscale environmental signals to shape riverine carbon cycling. Our study highlights the urgency of incorporating viral ecology into predictive frameworks of riverine biogeochemical cycling under accelerating environmental change. Full article

Pyrrolomycins and marinopyrroles are natural products originally derived from Streptomyces spp. that possess potent anti-infective activity against a variety of organisms, including drug-resistant bacteria and eukaryotic pathogens, especially pertinent amid the search for additional antimicrobial agents. These highly halogenated compounds have been proposed to act as protonophores, an uncommon mechanism of action that likely contributes to their broad-spectrum antibacterial activity. To improve efficacy and overcome limitations to clinical transition, promising derivatives of these natural compounds have been synthesized, introducing structural refinements that enhance pharmacological properties while preserving potent anti-infective activity. Recent discoveries demonstrate the potential of pyrrolomycins and marinopyrroles derivatives to serve as broad-spectrum anti-infective agents with efficacy against drug-resistant bacteria, bacterial biofilms, parasitic infections, and some viruses. Full article

Recent advances in next-generation sequencing have revealed that the virome—the set of viruses residing in the gastrointestinal tract—is a fundamental yet still underexplored component of the human intestinal ecosystem. Despite the prevalence of research focused on bacterial alterations, recent findings suggest a significant role for viral elements within the intestinal microbiota, namely latent viruses, bacteriophages and eukaryotic viruses, in influencing brain health. Alterations in the gut virome may, in particular, contribute to the processes underlying brain aging, cognitive decline, and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis (MS). This review highlights the potential of intestinal viruses to modulate gut barrier integrity, systemic immune response and neuroimmune inflammation. Such interactions could promote conditions of chronic neuroinflammation, alterations in synaptic plasticity, and neuronal vulnerability. A more comprehensive understanding of the role of the gut virome could potentially result in novel approaches to the early detection and treatment of neurocognitive disorders in adults and older individuals. Full article

Cryo-electron microscopy (cryo-EM) has revolutionized structural virology, enabling routine structure determination at 2–4 Å resolution, with exceptional cases reaching 1.56 Å. The structural diversity of viruses across vertebrate, plant, and insect hosts provides fundamental insights into infection mechanisms, host–pathogen coevolution, and therapeutic target identification. However, analysis of Electron Microscopy Data Bank entries reveals notable disparities in structural coverage: among 11,717 eukaryotic virus structures (excluding bacteriophages), vertebrate viruses constitute 97.6% (n = 11,432) of deposited entries, while plant viruses (1.0%; n = 117) and insect viruses (1.4%; n = 168) remain significantly underrepresented. This bias stems from distinct technical barriers including size limitations for giant viruses exceeding 200 nm, the loss of asymmetric information during symmetry-imposed processing, and the morphological complexity of filamentous and pleomorphic viruses. Each barrier has driven the development of specialized methodological solutions: block-based local refinement overcomes through-focus variations in giant viruses, cryo-electron tomography (cryo-ET) validates and reveals asymmetric features lost in symmetrized reconstructions, and subtomogram averaging enables structural analysis of pleomorphic assemblies. This review synthesizes recent methodological advances, critically evaluates their capacity to address specific technical barriers, and proposes strategies for expanding structural investigations across underrepresented host systems to achieve comprehensive understanding of viral structural biology. Full article

The human virome represents a fundamental yet understudied component of the microbiome, influencing immune regulation and disease. Given the profound immune dysregulation and microbial imbalance associated with HIV infection, understanding virome alterations during HIV and antiretroviral therapy is essential. This narrative review seeks to integrate and discuss the latest evidence regarding the structure and behavior of the human virome in healthy individuals, in the context of HIV infection, and under antiretroviral therapy. A comprehensive literature search was performed in MEDLINE and Google Scholar for peer-reviewed English-language articles published up to November 2025. Studies describing virome composition, diversity, and interactions in people living with HIV, as well as antiretroviral-induced changes, were included. Reference lists of relevant papers were screened to identify additional sources. Data were extracted and synthesized narratively, emphasizing human studies and supported by evidence from primate models where applicable. HIV infection induces profound alterations in the human virome, notably an expansion of eukaryotic viruses such as Anelloviridae, Adenoviridae, and Parvoviridae, accompanied by reduced bacteriophage diversity. Antiretroviral therapy partially restores virome balance but fails to fully re-establish pre-infection diversity, with persistent enrichment of Anelloviridae reflecting incomplete immune reconstitution. Virome perturbations correlate with immune activation, microbial translocation, and inflammation, contributing to comorbidities despite virological suppression. Emerging evidence suggests regimen-specific effects, with integrase inhibitor-based therapies showing more favorable viromic recovery. HIV and antiretroviral therapy profoundly remodel the human virome, with lasting implications for immune homeostasis and chronic inflammation. The ongoing disruption of the virome highlights its promise as both a biomarker and a potential therapeutic target in the management of HIV. Longitudinal, multi-omic studies are needed to clarify the causal role of virome alterations and guide future interventions. Full article