Search Results (219)

Understanding host cell response to viral infection could lead to the identification of molecular targets that can be used for the development of diagnostics and therapeutics. In this study, we investigated human dendritic cell (DC) response to infections with Vaccinia (VAC) virus, a highly immunogenic poxvirus, and Venezuelan Equine Encephalitis (VEE) virus, a single-stranded positive-strand RNA alphavirus, using human gene expression microarrays. Comparative changes in DC mRNA expression resulting from infection by the two viruses at 1, 8, and 12 h post-infection (hpi) revealed distinct temporal dynamics. VAC infection triggered early and robust activation of pathways related to chromatin organization, DNA damage, and antigen presentation, while VEE infection exhibited delayed activation of immune signaling pathways, including interferon signaling and cytokine production. Shared pathways, such as interferon signaling and inflammasome activation, highlight universal antiviral responses and potential therapeutic targets. These findings provide a molecular framework affected by VAC and VEE that need to be validated with additional experiments, such as functional assays or in vivo studies. The specific up- or downregulation of these pathways at different time points likely dictates the overall outcome of the viral infection and could potentially lead to better understanding of the temporal regulatory dynamics of virus host response. Full article

Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne pathogen causing low mortality but high morbidity in humans, with 4–14% cases exhibiting neurological complications. While the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS–STING) pathway is canonically associated with double-stranded DNA (dsDNA) detection, it has been shown to respond to RNA viruses and subsequently limit viral pathogenesis. Several viruses antagonize this signaling cascade, underscoring the importance that cGAS–STING plays in host immunity. Previous studies regarding single-stranded RNA viruses revealed that cGAS–STING limits viral replication in Old World alphavirus chikungunya virus infections, but little is known about New World alphaviruses such as VEEV. Here, we investigate the impact that STING activation has on VEEV infection as a potential prophylactic and therapeutic intervention. VEEV infection alone did not induce STING phosphorylation at Ser366, but interferon-stimulated genes (ISGs) were upregulated during the late phase of infection. Loss of STING through siRNA showed a partial dependency on STING for ISG transcription, suggesting that STING activation may occur through a noncanonical process. Priming of the STING pathway prior to infection was found to be critical in limiting viral replication; however, targeting STING activation post-infection abrogated the antiviral effects that dsDNA had on VEEV. VEEV suppressed STING phosphorylation in a multiplicity of infection (MOI)-dependent manner with the most robust pSTING (Ser366) inhibition observed at an MOI of 10. Collectively, our results suggest that VEEV antagonizes canonical STING activation. Full article

Autoimmune flares are often accompanied by abrupt surges of circulating plasmablasts—short-lived, high-output antibody-secreting cells generated through extrafollicular B-cell activation in response to microbial cues. Three categories of microbial input appear to repeatedly trigger these “plasmablast storms”: latent herpesvirus reactivations (Epstein–Barr virus, cytomegalovirus, human herpesvirus-6, varicella–zoster virus), acute respiratory or gastrointestinal infections including SARS-CoV-2, and chronic oral or gut dysbiosis. Although biologically distinct, these stimuli converge on innate sensing pathways driven by pathogen-associated molecular patterns such as unmethylated CpG DNA, single-stranded RNA, lipopolysaccharide, and bacterial lipoglycans. Through Toll-like receptors and type I interferon signalling, microbial signatures accelerate class switching, amplify inflammatory cytokine milieus, and lower B-cell activation thresholds, enabling rapid plasmablast mobilisation. Dysbiosis further maintains B cells in a hyper-responsive state by disrupting mucosal homeostasis and altering microbial metabolite profiles, thereby reducing the stimulus required to trigger plasmablast bursts. Once generated, these waves of oligoclonal plasmablasts home to inflamed tissues, where chemokine and adhesion landscapes shape their retention during flares. Emerging evidence suggests that such episodic plasmablast expansions promote autoantibody diversification, somatic hypermutation, and epitope spreading, progressively eroding tolerance. This review synthesizes these insights into a unified model in which infections and dysbiosis promote microbe-licensed plasmablast storms that influence the tempo and severity of autoimmune disease. Full article

Chicken anemia virus (CAV) is a single-stranded circular DNA virus classified within the genus Gyrovirus of the family Anelloviridae. The disease caused by CAV is predominantly characterized by aplastic anemia, lymphatic atrophy, and concurrent immunosuppression. The widespread occurrence of CAV has led to significant economic detriment in the global poultry sector. This review offers a thorough overview of advancements in CAV, encompassing its genomic features and transmission, clinical signs and pathogenicity, diagnostic methodologies, prevalence, and current antiviral strategies, which will provide a valuable resource for future research and the effective management of this pathogen. Full article

Beak and feather disease virus (BFDV) is a small, icosahedral, non-enveloped virus with a circular single-stranded DNA genome, that belongs to the Circoviridae family. BFDV is globally distributed and poses a major threat to susceptible avian populations. This underscores the urgent need for rapid and reliable molecular detection methods to monitor and control the spread of the virus. Quantitative PCR assays offer several advantages, including high sensitivity, specificity, and the ability to quantify viral load. Here, we report the development and validation of a quantitative real-time PCR assay using a TaqMan probe targeting the replicase gene to detect BFDV in psittacine blood samples. The assay demonstrates high sensitivity, specificity, and suitability for routine diagnostic use with an LOD and an LOQ of 10 and 30 plasmid copies, respectively, determined using a recombinant plasmid containing a BFDV genomic fragment. The assay achieved 98.8% sensitivity and 100% specificity. The method also demonstrated strong repeatability and reproducibility, with intra- and inter-assay coefficients of variation of 4.14% and 4.44%, respectively. Both values are well below the acceptance threshold. Overall, this TaqMan-based real-time PCR assay is a reliable, sensitive, and efficient diagnostic tool for detecting BFDV in psittacine samples. Full article

The Bactrian camel is a key economic livestock species in China and around the world. It yields meat and milk (high-quality functional foods), and the milk reports health benefits. Dromedary camels, as intermediate hosts of MERS-CoV, have garnered significant public health attention. In contrast, viral surveillance in Bactrian camels from the same genus as dromedaries has received limited attention, with only sporadic or regionally confined reports available. Systematic investigations into the virome of viral species, viral diversity, and novel viruses in Bactrian camels are lacking. In this study, swabs were collected from 701 Bactrian camels in China. Through metagenomics, 3262 viral contigs were classified into 16 viral phyla, 29 viral families, and an unclassified group. The different landforms were found to influence viral diversity and composition in Bactrian camels, with mountainous area exerting the greatest impact. The viral composition significantly differed between captive and free-ranging camels. The study identified at least 12 viruses with zoonotic potential, and phylogenetic analysis indicated cross-species transmission in some of them. Additionally, picornavirus, circular Rep-encoding single-stranded (CRESS) DNA virus, and polyomavirus from Bactrian camels may represent novel species or genotypes. To summarize, in this study, we described the baseline virome profile of Chinese Bactrian camels, investigated the ecological factors influencing the viral distribution of Bactrian camels, identified key potential viral risks, and provided a scientific basis for the prevention, control, and early warning of critical viral diseases in Bactrian camels from China. Full article

The human papillomavirus (HPV) is a small, non-enveloped virus with a circular double-stranded DNA genome. The HPV genome encodes the E2 activator protein, which is required for viral transcription. R-loops are triple-stranded nucleic acid structures that occur when newly synthesized single-stranded RNA anneals to duplex DNA. These structures form during papillomavirus transcription. We and others have demonstrated that resolution of viral R loops is crucial for HPV episomal maintenance. ZPR1 is a zinc finger protein that can recruit SETX to mammalian R-loops to mediate resolution. E2 binds to and recruits SETX, an R-loop helicase, to the viral promoter. We observed E2 in complex with SETX and ZPR1. However, we found that ZPR1 depletion decreased viral R-loops while enhancing cellular R-loops. ZPR1 depletion also increased SETX binding to the viral promoter. These data suggest that ZPR1 is not required for HPV R-loop resolution, in contrast to what has been observed in mammalian cells. We detected the E2 protein associated with R-loops and found that E2 overexpression increases cell-derived R-loop formation. Analysis of TCGA datasets revealed that ZPR1, but not SETX, mRNA expression is significantly reduced in HPV-positive cervical and head and neck cancers. Together, these findings indicate that while E2 mediates HPV R-loop resolution, it also promotes R-loop accumulation in the host genome, likely through SETX sequestration. Full article

Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous spectrum of disorders that lead to progressive and irreversible vision loss. Gene therapy is the most promising emerging treatment for IRDs. While gene augmentation strategies have demonstrated clinical benefit and results within the first approved ocular gene therapy, their application is restricted by adeno-associated virus (AAV) packaging capacity and limited efficacy for dominant mutations. Recent breakthroughs in precision genome editing, particularly base editing (BE) and prime editing (PE), have provided alternatives capable of directly correcting pathogenic variants. BE enables targeted single-nucleotide conversions, whereas PE further allows for precise insertions and deletions, both circumventing the double-strand DNA cleavage or repair processes typically induced by conventional CRISPR–Cas editing systems, thereby offering advantages in post-mitotic retinal cells. Preclinical investigations across murine and non-human primate models have demonstrated the feasibility, molecular accuracy, and preliminary safety profiles of these platforms in targeting IRD-associated mutations. However, critical challenges remain before clinical application can be realized, including limited editing efficiency in photoreceptors, interspecies variability in therapeutic response, potential risks of off-target effects, and barriers in large-scale vector manufacturing. Moreover, the delivery of genome editors to the outer retina remains suboptimal, prompting intensive efforts in capsid engineering and the development of non-viral delivery systems. This review synthesizes the current progress in BE and PE optimization, highlights innovations in delivery platforms that encompass viral and emerging non-viral systems and summarizes the major barriers to clinical translation. We further discuss AI-driven strategies for the rational design of BE/PE systems, thereby outlining their future potential and perspectives in the treatment of IRDs. Full article

Psittacine Beak and Feather Disease (PBFD) is a highly contagious viral condition caused by Circovirus parrot—commonly known as Beak and Feather Disease Virus (BFDV)—a small, single-stranded DNA virus of the family Circoviridae. The disease primarily affects parrots (order Psittaciformes) and is characterized by progressive feather dystrophy, beak deformities, immunosuppression, and high mortality rates, particularly in juvenile birds. Although PBFD was initially documented in Australian psittacines, the virus has now attained global distribution, facilitated predominantly by the international trade in live parrots, both legal and illegal. This review provides a comprehensive synthesis of current knowledge on the virology, clinical presentation, molecular epidemiology, and phylogeographic spread of BFDV. Particular attention is given to the role of parrot trade in shaping transmission dynamics and genetic diversification. The review further evaluates existing biosecurity policies, diagnostic challenges, and disease management strategies within both captive and wild avian contexts. Given PBFD’s dual status as a veterinary concern and a growing conservation threat, strengthening international surveillance, regulating wildlife trade, and integrating molecular diagnostics into routine screening are critical priorities. Effective containment of BFDV requires a multidisciplinary approach involving veterinarians, aviculturists, conservation biologists, and policymakers to safeguard the health and genetic viability of endangered psittacine species globally. Full article

Gemykibivirus, an emerging single-stranded DNA (ssDNA) virus of the recently established genus in the family of Genomoviridae, had been discovered in human blood and cerebrospinal fluid and a variety of other body fluids. However, the molecular mechanisms of gemykibivirus entrance into the host cells and its pathogenicity remain poorly understood. To investigate the host response of gemykibivirus, we used an infectious clone of gemykibivirus previously established through molecular biology techniques to rescue virus in HEK293T cells and analyzed the changes in the host transcriptome during the infection period by RNA-Seq. Our findings indicate that gemykibivirus can both express viral proteins and accomplish replication, and high-throughput transcriptome analysis identified a total 1732 significantly different genes. Functional enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for differentially expressed genes (DEGs) showed gemykibivirus involving several important pathways, including MAPK signaling pathway, Chemical carcinogenesis-reactive oxygen species and Oxidative phosphorylation. Interestingly, mitochondrial DNA-encoded mRNAs exhibited varying levels of upregulation, suggesting that gemykibivirus may be involved in mitochondrial fission and the regulation of mitochondrial function. Subsequently, a series of experiments proved that gemykibivirus can lead an increase in mitochondrial DNA copy number, promote the release of mtDNA into the cytoplasm, enhance reactive oxygen species production and trigger other cellular antiviral responses. Overall, we lay a foundation for revealing the relationship between Gemykibivirus and human diseases through mitochondrial functional alterations. Full article

Virus inactivation exhibits varying disinfection kinetics due to structural or genomic differences. Standard post-disinfection assessment relies on observing cytopathic effects in inoculated cell cultures, which are limited by sensitivity, availability, cost, and turnaround time. This study explores nucleic acid aptamers as molecular sensors to differentiate between intact and post-disinfection virus particles. To discover aptamers, 12 cycles of an automated SELEX (Systematic Evolution of Ligands by Exponential Enrichment) experiment were performed using recombinant (r)-VP2 protein of canine parvovirus (CPV). Enrichment of single stranded (ss) DNA binders was evaluated by sequencing the enriched libraries. The most abundant sequences were tested for binding with coated rVP2 and CPV (intact and treated with heat and peracetic acid (PAA) disinfectant) followed by detection using PCR. Binding specificity was assessed using intact and heat-treated feline panleukopenia virus (FPV) and porcine parvovirus (PPV). Sequencing of the DNA libraries from selection cycle 6 and cycle 12 products showed individual sequence enrichment with maximum frequencies of 2.14% and 8.65%, respectively. The top three abundant sequences from each cycle confirmed rVP2 binding. In the case of CPV, only heat-treated and PAA-treated CPV showed binding to the candidate sequences. However, reduced binding to the CPV-specific antibody was observed for rVP2 and treated CPV compared to intact CPV. No apparent binding of the tested sequences was observed for FPV and PPV. Aptamers binding to denatured but not intact CPV demonstrate the potential to distinguish between the two states, providing a basis for developing a molecular assay to assess disinfection efficacy. Full article

Porcine parvovirus (PPV), a non-envelope single-stranded DNA virus, causes severe reproductive disorders in swine worldwide, characterized by fetal mortality, mummification, and reduced boar fertility. As a highly prevalent pathogen in Chinese swine herds, PPV imposes substantial economic burdens on intensive pig production systems. This review systematically synthesizes recent advances in PPV virology, focusing on genomic evolution of emerging strains (PPV1–PPV8), epidemiological dynamics of emerging strains, molecular pathogenesis, and novel diagnostic tools. Furthermore, we critically evaluate current vaccine strategies, highlighting their limitations in cross-protective efficacy and viral shedding control. By integrating multi-omics insights with immunological profiling, this work delineates actionable pathways for next-generation vaccine design and proposes a roadmap for rational antigen selection. This review consolidates foundational knowledge and establishes a translational bridge between basic virology and prevention and control of porcine parvovirus, addressing critical gaps in porcine reproductive disease management. Full article

Nile tilapia (Oreochromis niloticus) is an indispensable source of high-quality protein worldwide. Along with the exponential expansion of tilapia aquaculture, several novel pathogenic viruses have emerged, and some cause significant economic losses. Unfortunately, there is scarce information on the biology and epidemiology of these viruses. This exploratory metagenomic study used Oxford Nanopore Technology (ONT) sequencing to profile the virome compositions of both wild and farmed Nile tilapia across five regions in Egypt. The Nile tilapia virome was dominated by two double-stranded DNA bacteriophages, Muvirus mu and M. sfmu, which constituted 79.8% of the detected sequences. Eukaryotic viruses, including members of the families Amnoonviridae, Peribunyaviridae, and Baculoviridae, were also identified. Two giant DNA viruses known to infect Acanthamoeba spp., Mollivirus sp., and Pandoravirus sp. were identified in the spleen virome of tilapia from a single sampling site. The diversity analysis showed no significant differences among tissue types or sampling sites. Phylogenetic analyses were performed on a single virus detected of potential pathogenicity, an amnoonvirus. The analyses demonstrated that the detected virus is a member of the family Amnoonviridae and placed it alongside members of the Tilapinevirus genus. The virus, however, was distinct from the other two members in the genus: T. tilapae and T. poikilos. This study underscores the usefulness of ONT in providing a foundational understanding of the Nile tilapia virome. Full article

Minute virus of canines (MVC), which is a member of the Bocaparvovirus genus, is a non-enveloped, single-stranded DNA virus that causes respiratory and gastrointestinal disease in canines, as well as causing infertility and fetal death in pregnant dogs. The non-structural small protein NP1 of bocaparvoviruses is a unique feature that distinguishes the bocaparvovirus subfamily from other parvovirus subfamilies. In the life cycle of the MVC, NP1 plays an indispensable role in viral DNA replication and pre-mRNA processing. Currently, there is a paucity of studies reporting the characterization of host cell proteins interacting with NP1 during MVC replication. In this study, we screened and identified host cell proteins interacting with MVC-NP1 through immunoprecipitation (IP) combined with liquid chromatography and tandem mass spectrometry (LC-MS/MS) analysis; MCM7 (Mini-chromosome Maintenance Protein 7) has been identified and confirmed to interact directly with NP1 through its N-terminal domain. Furthermore, functional studies reveal that MCM7 is essential in MVC replication. The knockdown of MCM7 decreased the expression of this MVC protein significantly, as well as suppressing MVC replication by arresting the cell cycle in the G0/G1 phase during infection. Conversely, up-regulating MCM7 can rehabilitate the expression of MVC proteins, as well as supporting MVC replication. In conclusion, this study elucidates the interaction between the NP1 protein of MVC and the host factor MCM7, demonstrating that MCM7 is a key factor in the replication process of MVC. These findings provide a potential target for future antiviral therapy. Full article

Background/Objectives: Parvovirus B19 (B19V) is a non-enveloped single-stranded DNA virus transmissible by blood transfusion, with potentially severe outcomes in immunocompromised and pregnant recipients. In this study, we investigated the B19V prevalence in 441,084 blood donations from Salzburg, Austria, collected between 2012 and 2024, focusing on changes in epidemiological dynamics before, during, and after the SARS-CoV-2 pandemic. Additionally, the B19VB19V persistence and its implications for deferral policies were assessed. Methods: Donor samples were screened for B19VB19V DNA by qPCR (2012–2024) and for SARS-CoV-2 total anti-N antibodies (2020–2024). B19VB19V prevalence rates, cycle threshold (Ct) values, and seasonal distribution were compared between pre-pandemic, pandemic, and post-pandemic phases. Follow-up testing of initially B19VB19V-positive donors was performed after a 2-year deferral period. Results: The B19VB19V positivity rate of 0.13% (2012–2019) significantly decreased to 0.02% during the SARS-CoV-2 pandemic (2020–2022). A substantial increase occurred post-pandemic, with prevalence reaching 1.47% in 2024. Significant lower Ct values were observed in the post-pandemic phase, indicating higher viral loads. Additionally, younger donors (aged 18–45 years) showed significantly lower Ct values. After a 2-year deferral, 39% of re-tested donors remained B19VB19V DNA-positive. Conclusions: B19VB19V circulation increased substantially after the SARS-CoV-2 pandemic. Our observation is consistent with international reports and is likely due to an ‘immunity debt’ that has been accumulated due to pandemic-related public health interventions. Targeted B19VB19V screening and strict deferral strategies may be warranted particularly during outbreak periods to protect high-risk transfusion recipients. Full article