Search Results (5,168)

The ubiquitin-proteasome system (UPS) constitutes a highly conserved regulatory hub governing protein turnover and signal transduction in eukaryotes, which precisely determines the fate of substrate proteins via dynamic and reversible ubiquitination. During long-term coevolution between plants and viruses, the UPS has evolved into a critical battlefield for host–virus arms races. Plants exploit the substrate recognition specificity and proteolytic activity of the UPS to selectively eliminate essential viral proteins required for infection, thereby establishing multilayered antiviral immune barriers. In contrast, viruses have evolved diverse effector proteins to antagonize or hijack this pathway to facilitate their replication and spread. Competitive exploitation of this shared regulatory machinery underlies the fundamental logic of bidirectional regulation in plant–virus interactions. This review systematically summarizes the molecular basis of UPS-mediated plant antiviral immunity, as well as convergent pathogenic strategies adopted by diverse viruses to perturb ubiquitin signaling, suppress host immune responses, and reprogram the intracellular environment. The work aims to provide theoretical insights for deciphering viral pathogenesis and breeding crops with durable virus resistance. Full article

Water scarcity is driving increasing interest in potable water reuse, particularly in arid regions. However, inadequately treated reclaimed water may pose health risks from waterborne pathogens, including gastrointestinal infections. This study applied quantitative microbial risk assessment (QMRA) to estimate infection risks associated with Escherichia coli (E. coli), Cryptosporidium, rotavirus, and adenovirus using pilot-scale data from El Paso Water’s Pure Water Center advanced purification facility. Pathogen concentrations in source and treated water were fitted to probability distributions and incorporated into a probabilistic Monte Carlo QMRA framework to estimate exposure doses, daily and cumulative infection risks, and treatment performance (expressed as log reduction values (LRVs)) and were compared to U.S. Environmental Protection Agency (EPA) drinking water risk thresholds. E. coli demonstrated the greatest treatment effectiveness, with a median daily treated water infection risk of 1.45 × 10⁻⁶ and a median LRV of 3.32. Cryptosporidium demonstrated limited reduction in infection risk (median LRV = 0.976), while rotavirus demonstrated minimal reduction following treatment. Although adenovirus infection risk decreased after treatment, the residual risk remained high. Viral risk estimates were strongly influenced by non-detects and limited observations. These findings highlight the importance of robust monitoring and probabilistic QMRA approaches for evaluating uncertainty and treatment performance in advanced potable reuse systems. Full article

Neuraminidase (NA) is a major surface glycoprotein of influenza viruses that mediates the release of progeny virions from infected cells. Although both hemagglutinin (HA) and NA are targets of protective immune responses, current seasonal influenza vaccines are primarily standardized based on HA content, resulting in variable and often suboptimal induction of NA-specific immunity. Therefore, NA is subject to different immune pressures and exhibits distinct patterns of antigenic evolution. Increasing evidence suggests that neuraminidase-inhibiting (NAI) antibodies contribute to protection against influenza by limiting viral replication and reducing disease severity, particularly when HA antibodies are poorly matched to circulating strains. The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses with widespread transmission in dairy cattle and increasing zoonotic infections has renewed interest in understanding the extent of pre-existing human immunity to NA and its potential role in mitigating disease caused by emerging influenza viruses. However, the breadth of cross-reactive NA immunity against zoonotic influenza viruses remains incompletely understood. In this review, we summarize current knowledge of population immunity to influenza NA, with a focus on the roles of immune imprinting, natural infection, and seasonal vaccination in shaping NA-specific antibody responses. We further discuss the cross-reactivity of these antibodies against zoonotic influenza viruses and highlight the implications of NA immunity for pandemic preparedness. Full article

Cynoglossus semilaevis papillomavirus (CsPaV) is an emerging viral pathogen associated with high mortality in farmed Chinese tongue soles. A sensitive, specific, and quantitative method is needed for CsPaV surveillance and epidemiological studies. In this study, we designed primers and a probe that targeted the CsPaV L1 gene. We then established a TaqMan probe-based quantitative PCR (qPCR) assay. The assay detected as few as 5.8 × 10¹ copies/µL and was 1000-fold more sensitive than conventional PCR. The assay did not cross-react with the other aquatic pathogens tested. The intra-assay coefficients of variation ranged from 0.23% to 0.84%, and the inter-assay coefficients ranged from 0.56% to 1.48%. These results showed that the assay had good repeatability. We used the assay to study the tissue distribution and temporal dynamics of CsPaV after experimental infection. Healthy Chinese tongue soles received an intraperitoneal injection of 300 µL of inoculum containing 3.66 × 10⁵ CsPaV copies/µL. Three fish were sampled at 1, 2, 3, 5, and 7 days post-infection. CsPaV DNA was detected in all tissues examined. The kidney had the highest viral DNA load, which reached 2.47 × 10⁷ copies/mg at 7 days post-infection. Among 176 clinically diseased Chinese tongue soles collected between 2023 and 2026, 80.68% tested positive for CsPaV. CsPaV DNA was also detected in several other aquatic species. These findings provide a sensitive tool for CsPaV surveillance and molecular epidemiological studies. The assay may also support disease prevention and control in Chinese tongue sole aquaculture. Full article

The occurrence of viral zoonotic spillover (the transmission of viruses from animals to humans) has attracted worldwide attention due to mounting concerns regarding viral threats such as avian influenza, Hendra, monkeypox, Nipah and bat coronaviruses. It is evident that these events deviate significantly from natural occurrences, being the conflation of ecological, environmental and social factors that are profoundly altering the boundaries between the animal and human domains. Consequently, in order to comprehend both the contemporary and prospective drivers of zoonotic viral spillover, a coordinated, comprehensive global One Health response is essential. The purpose of the present review is to analyze prevailing pathways of transmission between animal reservoirs and human populations. This examination involves the analysis of historical cases, including those of SARS and Ebola, as well as recent occurrences, such as the global pandemic of SARS-CoV-2 (COVID-19). A secondary objective of this review is to comprehend the fundamental mechanisms of cross-species transmission. The development of effective strategies to mitigate the emergence of zoonotic viruses and prevent future pandemics is contingent on a robust understanding of these mechanisms. This analysis is key to identifying pandemic pathogens and preventing the spread of zoonotic viruses. In conclusion, the review provides a thorough evaluation of current global strategies to prevent the spread of zoonotic viruses, highlighting gaps in our understanding and areas for further research. Full article

Highly pathogenic avian influenza H5N1 virus (H5N1 HPAIV) has long circulated in wild waterfowl and poultry and continues to cross species barriers, posing sustained threats to livestock productivity and public health. The 2024 outbreak of H5N1 HPAIV in dairy cattle across multiple U.S. states represents the first recognized large-scale transmission event of this virus in ruminants, reshaping our understanding of its host range and transmission ecology. This review summarizes recent advances in the epidemiology, virological characteristics, transmission, pathogenesis, surveillance, and control of dairy cattle-associated H5N1. The initial multistate outbreak was dominated by clade 2.3.4.4b genotype B3.13, whereas subsequent independent introductions of genotype D1.1 demonstrated that repeated avian-to-cattle spillover also contributes to the evolving outbreak ecology. A defining feature is efficient replication in bovine mammary epithelial cells, resulting in high viral titers in milk, supporting milk-associated exposure and milking-related contamination as plausible components of transmission, although the relative contribution of different routes remains unresolved. Infected cattle typically show reduced feed intake, a marked decline in milk production, abnormal milk, and mild systemic signs, whereas severe respiratory disease and mortality are uncommon. Mutations such as PB2-M631L, PA-K497R, and changes in NP and NS1 may promote replication and immune evasion in bovine cells, while genotype-specific PB2 adaptations highlight the potential for further mammalian adaptation. Human infections reported to date have been predominantly mild and associated with occupational exposure, with no evidence of sustained human-to-human transmission. Experimental vaccine studies have begun to demonstrate immunogenicity in cattle, although protection against mammary infection, viral shedding, and transmission remains to be established. Future priorities include clarifying mammary tropism and transmission dynamics, while strengthening diagnostics, farm biosecurity, vaccination, evaluating cattle vaccination strategies, and integrated One Health surveillance. Full article

Background: Precision diagnostics are more and more important in intensive care units (ICUs), where rapid identification of infectious agents and antimicrobial resistance determinants is crucial for timely and appropriate treatment. Conventional microbiological methods are frequently limited by long turnaround times and reduced sensitivity, which may delay appropriate treatment. Nanopore sequencing allows rapid, direct, and long-read sequencing of DNA/RNA molecules without the need for amplification, avoiding biases introduced by NGS during amplification and library preparation and generating data in real time. Objectives: This narrative review aims to summarize current knowledge of nanopore technology in the ICU, discuss nanopore principles and current clinical applications in intensive care medicine, highlight its advantages and limitations, and explore future perspectives for integrating nanopore-based diagnostics into precision critical care. Methods: A literature search was performed using PubMed and Web of Science. The literature search was conducted with no lower restriction, covering English-language publications. Results: Nanopore sequencing enables real-time, long-read, single-molecule analysis of native nucleic acid molecules, rapid pathogen identification, antimicrobial resistance profiling, metagenomic analysis, and direct sequencing without amplification. Recent studies have proved the clinical utility of nanopore sequencing in critically ill patients with sepsis, bloodstream infections, hospital-acquired pneumonia, ventilator-associated pneumonia, and fungal and viral infections. Its portability, rapid turnaround time, and potential for point-of-care implementation make it particularly attractive for ICU settings. Conclusions: Nanopore sequencing technology represents a promising molecular diagnostic tool, but wider clinical implementation warrants further larger studies with clinical outcome endpoints, standardized bioinformatic pipelines, and clearer validation pathways. Full article

Background/Objectives: Epstein–Barr virus (EBV) is a ubiquitous pathogen responsible for significant malignancies and autoimmune diseases, yet no prophylactic vaccine is available. The viral entry glycoproteins gL/gH and gB are essential for infection, but soluble forms are poorly immunogenic and fail to elicit durable neutralizing antibodies. Moreover, EBV infects both B cells and epithelial cells, demanding broad neutralization. This study aimed to develop a virus-like particle (VLP) platform that displays gL/gH and gB in a dense, repetitive array to overcome these barriers. Methods: We conjugated recombinant gL/gH and gB to Acinetobacter phage AP205 VLPs using SpyTag/SpyCatcher covalent linkage, generating monovalent and bivalent chimeric nanoparticles (co-displaying both antigens on the same particle). Mice were immunized with these VLP constructs or alum-adjuvanted soluble proteins, and antibody responses, neutralization titres against B-cell and epithelial-cell infection, as well as germinal centre responses and durability, were assessed over a four-month period. Results: AP205-conjugated nanoparticles elicited significantly higher antigen-specific IgG titres than soluble proteins. The chimeric VLP, co-displaying gL/gH and gB, induced the stronger neutralising antibodies, effectively blocking EBV entry into both B cells and epithelial cells. Mechanistically, VLP immunization drove robust and sustained germinal centre reactions, resulting in increased plasma and memory B cells, and maintained neutralising activity for at least four months. Conclusions: Precision nanoscale assembly of EBV entry glycoproteins on a synthetic VLP programs high-magnitude, broad-spectrum, and durable humoral immunity. The AP205-SpyTag platform offers a versatile and promising strategy for developing an effective prophylactic EBV vaccine. Full article

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen that causes substantial livestock losses and a range of severe human illnesses, including hemorrhagic disease, hepatitis, retinitis, vision loss, and delayed encephalitis. Despite its public health and One Health importance, no approved RVFV-specific antiviral therapy or licensed human vaccine is available. Therapeutic development is challenged by the progression of RVFV disease from acute viremia and hepatic injury to delayed neurologic and ocular complications, highlighting the need for countermeasures that protect both systemic organs and CNS tissues. This review examines RVFV antiviral development in the context of neuroinvasive disease. We summarize evidence on RVFV neuroinvasion and central nervous system injury, including route-dependent entry, blood–brain barrier interactions, immune responses, neuroinflammation, and neuronal damage. We then evaluate major antiviral strategies by mechanism, treatment timing, tissue exposure, and central nervous system relevance. Finally, we propose that future RVFV therapeutics are assessed not only by survival, viremia, and hepatic viral-load endpoints, but also by blood–brain barrier penetration, brain pharmacokinetics, efficacy in neuroinvasive models, delayed-treatment activity, and protection against encephalitis-associated injury. This framework may help prioritize antivirals that control both acute systemic disease and delayed neurological complications. Full article

Banana bunchy top virus (BBTV) is a devastating pathogen threatening global banana production. The plant ubiquitin–proteasome system (UPS) governs immune signaling and is frequently subverted by invading viruses, yet the molecular mechanism through which BBTV interferes with host UPS remains unclear. Here, we show that BBTV nuclear shuttle protein (NSP) serves as the core viral effector to disrupt banana ubiquitination homeostasis. RT-qPCR time-series assays confirmed that BBTV infection dynamically remodels the transcription of eight phylogenetically divergent RING-type E3 ubiquitin ligases: four subfamily I E3-SIS3 paralogs and E3-HIP1 are significantly upregulated at 14 dpi and 21 dpi, while E3-BOI and E3-RHA1B are suppressed at 21 dpi. Transient expression screening of all six BBTV-encoded proteins verified that only NSP reproduces the UPS perturbation signature triggered by viral infection. Cross-species sequence alignment identified an evolutionarily conserved FNGSF motif within NSP orthologs of all Nanoviridae members. Alanine substitution mutagenesis (NSP^AAAAA) completely abolished NSP’s capacity to alter E3 ligase transcription. Western blot assays further validated that wild-type NSP induces massive accumulation of ubiquitinated host proteins, whereas the FNGSF-deficient mutant does not disrupt cellular ubiquitination. Phylogenetic analysis revealed that NSP-targeted E3 ligases share low overall sequence similarity but retain conserved catalytic RING domains, indicating that NSP exerts broad-spectrum regulatory effects on host UPS via the FNGSF motif. Collectively, this study reveals a novel pathogenic strategy whereby BBTV NSP recruits diverse host RING E3 ligases via its conserved FNGSF motif to dysregulate plant ubiquitination and elicit plant pathogenicity. Our findings provide two promising targets—the NSP FNGSF motif and defense-associated E3-SIS3 ligases—for developing antiviral agents and breeding BBTV-resistant banana germplasm. Full article

Senecavirus A (SVA), an emerging causative agent of porcine vesicular disease, belongs to the genus Senecavirus of the family Picornaviridae. The virus has been circulating in pig herds in the USA dating back to 1988, evolved into clinically significant pathogenic SVA variants causing a pandemic in the USA and Canada since 2014, and thereafter gradually spread to the Americas and Asia. To date, most studies have illustrated the infection dynamics, epidemiology, diagnostic methods, and vaccine development, yet the molecular pathogenesis of SVA remains incompletely characterized. As a novel picornavirus capable of establishing persistent subclinical infections, SVA has been detected in tissues such as tonsils and testicles for up to 156 days post-infection, posing a substantial challenge to swine health and production systems. In parallel, SVA has gained attention as an oncolytic virotherapy candidate for neuroendocrine tumors due to its tumor-selective tropism. Therefore, elucidating the mechanisms underlying SVA pathogenesis will not only support the development of effective countermeasures for swine but also inform the engineering of recombinant variants with enhanced therapeutic potential for human oncology. This review comprehensively summarizes the current knowledge on viral and host determinants of SVA pathogenesis, from the viral genome, evolution, and recombination to ANTXR1 host immunity, and programmed cell death, and presents future research directions, aiming to identify key knowledge gaps to guide future studies on SVA. Full article

Ticks are prominent hosts for many viruses that are pathogenic to humans on almost every continent. Despite the documented historical association of ticks with viral disease in humans, clinical case reports are low, likely due to under-recognition of these pathogens. A key feature of understanding tick-borne virus transmission to humans lies in the natural invertebrate and vertebrate hosts supporting ecological maintenance. As humans are often infected as incidental hosts during the tick–virus life cycle, determining relevant ticks and mammals involved in maintenance can inform prevention strategies, surveillance priorities, and diagnostic assay development. This review aims to cover common trends in tick-borne virus ecology, including the wide breadth of implicated tick species, an unclear role for definitive vertebrate reservoirs, and the focal distributions of these viruses closely linked to these host ecological features. Here we also provide examples of prominent tick-borne viruses causing human disease between the Old (Africa, Asia, Europe) and New (Americas) Worlds, highlighting parallels in initial discoveries, vectors, and vertebrates including tick-borne encephalitis, Crimean–Congo hemorrhagic fever, severe fever with thrombocytopenia syndrome, Colorado Tick fever, and Powassan, Heartland, and Bourbon viruses. Full article

Background/Objectives: Nipah virus (NiV) is a highly pathogenic zoonotic agent that causes fatal respiratory and neurological diseases, for which no approved vaccines are currently available. To address this unmet need, we developed and evaluated novel mRNA-LNP vaccine candidates. These vaccines employ an epitope- and structure–guided “immune-focusing” strategy, aiming to maximize the exposure of critical neutralizing epitopes on the viral attachment (G) and fusion (F) glycoproteins. Methods: Head-to-head dimeric antigens (2Gs and 2Fs) were engineered by removing subdominant stalk regions and tandemly duplicating epitope-rich globular head domains. Three LNP-encapsulated candidates-NV1 (encoding 2Gs), NV2 (encoding 2Fs), and NV3 (a 1:1 mixture of NV1 and NV2)-were evaluated in BALB/c mice and Syrian hamsters to systematically assess humoral responses, cytokine secretion, BCR/TCR repertoires, and systemic safety. Results: NV1 and NV3 induced potent binding antibodies and strong neutralizing activity against NiV pseudoviruses. Meanwhile, although NV2 lacked neutralizing activity, it induced superior Th1-biased cellular immunity, accompanied by extensive T-cell clonal proliferation. BCR/TCR sequencing revealed unique adaptive immune characteristics that perfectly align with the distinct immunogenic properties described above. Preliminary safety assessments found no toxicity to vital organs, while active germinal center formation confirmed the success of immune mobilization. Conclusions: An epitope-centered dimer design effectively shapes the unique defense mechanisms of the adaptive immune system. NV3 offers a balanced and synergistic strategy that combines potent humoral and cellular immune defenses, providing a highly promising platform for the development of a Nipah virus (NiV) vaccine. Full article

Sexually transmitted infections (STIs) are common and probably underreported causes of proctitis and colitis. Bacterial (chlamydia, gonorrhoea, syphilis, Mycoplasma genitalium), viral (herpes simplex virus, mpox), and amoebic (Entamoeba histolytica) pathogens can cause inflammatory proctitis or colitis, which, depending on the pathogen, can mimic inflammatory bowel disease both on endoscopy and histopathology. Rectal and colonic masses are uncommon, but important manifestations of these infections, especially with chlamydia, syphilis, and E. histolytica. Testing for HIV is important in this context, since it allows for the inclusion of opportunistic pathogens into the differential diagnosis. Chronic diarrhoea can be a feature of chronic HIV infection. Enteric pathogens, such as Salmonella spp., Shigella spp., or Campylobacter spp., can be transmitted during sex, especially during oral–anal contact (“rimming”). The most common STI, human papillomavirus, is not associated with colitis, but is important because of its causal association with genital warts and anal cancer. Full article

Wildlife surveillance contributes to the detection of pathogens of veterinary and zoonotic importance. The red fox (Vulpes vulpes), which is well adapted to human-modified environments, is frequently included in wildlife pathogen surveillance. This preliminary study screened 20 opportunistically collected red fox carcasses from three neighboring areas of Pisa Province, Italy, for selected viral pathogens, including hepatitis E virus (HEV), canine adenovirus (CAdV), canine circovirus (CanineCV), canine parvovirus (CPV), canine coronavirus (CCoV), and canine bocavirus (CBoV), using an integrated serological, molecular, histopathological, and immunohistochemical approach. Five of 20 serum samples showed ELISA reactivity above the applied positive threshold, while two yielded equivocal results. One fecal sample produced an amplification product of the expected size in the HEV nested RT-PCR assay, but Sanger sequencing did not confirm HEV identity. Sequence-confirmed molecular analysis identified CAdV-1 in the liver and CCoV in the feces of the same fox, whereas CPV, CanineCV, and CBoV were not detected. Histopathological findings were nonspecific, and HEV and CAdV immunohistochemistry yielded negative results. These findings represent limited local observations from an opportunistically collected sample and may help inform the design of larger, systematically sampled investigations in red foxes. Full article