Search Results (2,476)

The major histocompatibility complex (MHC) represents a critical genetic locus that orchestrates adaptive immune responses through antigen presentation and T cell activation, characterized by exceptional polymorphism and species-specific diversity. In herbivores, MHC polymorphisms constitute fundamental determinants of resistance to parasitic, viral, and bacterial infections while serving as crucial indicators of genetic diversity and breeding value in animal populations. Recent advances in high-throughput sequencing technologies, single-cell omics, and population genetics have substantially advanced understanding of MHC gene structure, allelic polymorphism, evolutionary patterns, and associations with disease susceptibility and vaccine responsiveness. This comprehensive review systematically examines the structural characteristics and regulatory mechanisms of MHC genes, their associations with infectious disease resistance, their role in vaccine responses, and their practical applications in molecular breeding programs, conservation genetics, and immunological research. We identify current technical limitations and outline future research directions to establish a robust theoretical foundation for disease resistance breeding and immune regulation strategies in herbivore populations. Full article

The accurate characterization of human immunodeficiency virus (HIV) genetic diversity and drug resistance is critical for effective surveillance and treatment, yet current sequencing technologies face limitations in sensitivity and scalability for community-level implementation. We present G-HIV, an integrated platform combining long-read sequencing (G-seq500) with an automated bioinformatics pipeline. G-HIV processes raw FastQ data to generate automated reports on point mutations, drug resistance predictions, viral quasispecies diversity, and haplotype networks via a two-step analytical approach. Applied to 44 HIV-1 plasma samples (42 used in the final comparison after excluding 2 samples with low-quality Sanger chromatograms), G-HIV detected 3–48 candidate minority variants per sample that were not observed by Sanger sequencing, identifying drug-resistant quasispecies in two samples with undetectable Sanger signals, and revealed mixed infection cases (e.g., inter-subtype CRF07_BC/CRF08_BC) through phylogenetic analysis. G-HIV addresses an integration of long-read sequencing with a fully automated, one-stop bioinformatics pipeline designed for frontline laboratories without specialized bioinformatics expertise—providing a scalable solution for community-based resistance surveillance and personalized therapy optimization in resource-limited settings. This research addresses an integrated long-read sequencing and automated bioinformatics platform for rapid and precise HIV-1 surveillance. G-HIV surpasses conventional approaches like Sanger sequencing in resolution, efficiency, and accessibility for community-level surveillance. By integrating long-read sequencing, streamlining workflows and eliminating the need for specialized bioinformatics expertise, G-HIV is positioned to become a new solution, providing more effective one-stop services for HIV-1 prevention and control. 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

Human immunodeficiency virus (HIV) is an enveloped virus with a remarkable capacity for genetic diversification, enabling rapid escape from host immune responses and therapeutic interventions. Despite extensive global efforts, the development of an effective vaccine has remained elusive owing to the virus’s high genetic variability and antigenic diversity. Consequently, considerable effort has been directed toward the development of therapeutic agents targeting viral entry, reverse transcriptase, integrase, protease, and more recently, capsid. Although antiretroviral therapy (ART) remains the cornerstone of HIV treatment, it is associated with challenges including drug resistance, adverse side effects, and limitations in access and affordability. Targeting viral entry offers distinct advantages by blocking infection at the earliest stage of the viral life cycle and enabling the neutralization of free virions, as well as Fc-mediated elimination of HIV-infected cells in some cases. This review highlights promising protein-based HIV entry inhibitors that have demonstrated efficacy in preclinical studies, and discusses ongoing efforts to optimize their valency, avidity, specificity, serum half-life, effector functions, and production platforms to improve their therapeutic potential and economic feasibility. Full article

Infections caused by flaviviruses, including dengue virus (DENV), Zika virus (ZIKV), and West Nile virus (WNV), can lead to severe hemorrhagic or neurological disease. Antibody-dependent enhancement (ADE) remains a major obstacle to the development of safe flavivirus vaccines and antibody-based therapeutics. ADE includes ADE of infection, in which antibodies increase in viral entry, replication, or infection load, and ADE of disease, in which antibody-dependent inflammatory and immunopathological responses exacerbate disease severity. Previous reviews have largely addressed the general virological and immunological mechanisms of ADE, but few have integrated antibody isotypes and subclasses, Fc-region modifications, Fc receptor diversity, host FcγR polymorphisms, and complement activation within a translational framework. Consequently, how these factors jointly shape ADE of infection, progression to ADE of disease, and individual risk remains incompletely understood. Here, we synthesize evidence linking antibody properties, Fc receptor expression and signaling, FcγR genetic variation, and complement regulation to both forms of ADE. We then discuss how these findings can inform antigen selection, Fc engineering, complement-informed intervention, and systems serology-based risk stratification. By connecting mechanistic evidence with vaccine and therapeutic development, this review offers a framework for designing safer flavivirus interventions and advancing individualized assessment of ADE risk. Full article

ISG15 is an interferon-induced ubiquitin-like protein that exerts diverse functions during viral infection. We previously reported that ovine ISG15 (oISG15) promoted bluetongue virus (BTV) replication by stabilizing viral NS1 and VP4 in an ISGylation-independent manner, although the mechanism remained unknown. Here, using the generated anti-oISG15 antibody, we performed immunoprecipitation (IP) coupled with label-free Liquid Chromatography-Tandem Mass Spectrometry (LC–MS/MS) to characterize the oISG15-associated proteome in BTV-infected and uninfected cells. The results showed that BTV infection markedly remodeled the oISG15 association landscape, with decreased enrichment of several autophagy- and trafficking-related proteins and increased enrichment of mitochondrial metabolic proteins in oISG15 immunoprecipitates. Functionally, oISG15 overexpression induced modest alterations in autophagy-related markers in uninfected cells yet attenuated these markers’ abundance during BTV infection. Together, this study revealed BTV-induced changes in the oISG15-associated proteome that coincided with alterations in autophagy-related markers. Full article

The orthoflavivirus capsid (C) protein is a multifunctional protein that plays essential roles throughout the viral life cycle. Besides viral RNA encapsidation for nucleocapsid assembly, it associates with lipid droplets, interacts with host proteins, and translocates to the nucleus, although its nuclear functions are still poorly understood. How these diverse activities are coordinated remains an open question. Post-translational modifications (PTMs), which are key regulators of protein function, have emerged as critical modulators of the infection cycle in many RNA viruses. However, little is known about the occurrence and functional significance of PTMs in orthoflavivirus C proteins. Here, we review the current evidence on PTMs in orthoflavivirus C proteins and integrate insights from studies of other RNA viruses to propose mechanisms by which PTMs may regulate C protein function. To complement this review, we performed a comparative in silico analysis of predicted PTM sites in the C proteins of dengue, Zika, West Nile, and Japanese encephalitis viruses. By integrating PTM predictions with experimentally validated modification sites, residue conservation, and structural mapping, we identified conserved regulatory hotspots that represent promising targets for future experimental validation. Together, these findings highlight PTMs as an underexplored regulatory mechanism in orthoflavivirus capsid biology and provide a framework for future mechanistic investigations. Full article

Vibrio parahaemolyticus is a leading cause of seafood-associated gastroenteritis, yet the ecological and genomic significance of environmental populations as potential reservoirs remains incompletely characterized. From May to October 2024, 108 water samples were collected monthly at one coastal and two estuarine sites in Haiyan, Zhejiang. Confirmed isolates (n = 39) underwent whole-genome sequencing, MLST/cgMLST, virulence and AMR gene screening, integron characterization with BLASTp (+2.17.0) integrase family typing, and viral-region prediction. Culture-based detection was absent in May and rose to 66.7% in October (Cochran–Armitage trend, p = 0.003), with descriptively higher detection at the coastal site. MLST identified 28 STs including four novel types (Simpson’s diversity = 0.953). All isolates lacked tdh, trh, and T3SS2 but retained T3SS1 and MAM7. One estuarine isolate carried CALIN-associated dfrA31 and qnrVC5. All integrases matched VpaIntIA (95.9–100% identity), not mobile class 1–3 integrases. Viral regions were detected in 38/39 isolates; filamentous phage annotations in 52.6%. Haiyan coastal V. parahaemolyticus shows seasonal and spatial patterns, high diversity, and a mobilome dominated by chromosomal super-integrons, underscoring the need for integrase family typing in environmental surveillance. Full article

(1) Background: Bovine viral diarrhea virus (BVDV) is an economically important pathogen affecting cattle worldwide. The genetic diversity of BVDV-2 in buffalo remains poorly understood. This study aimed to elucidate the genomic and antigenic features of GX24, the first BVDV-2b isolate identified from dairy buffalo in China. (2) Methods: The virus was isolated from a rectal swab through three blind passages in MDBK cells and identified through immunofluorescence and RT-PCR. The near-complete genome was sequenced using the Illumina platform and subjected to phylogenetic and recombination analysis. B-cell epitopes and glycosylation sites were predicted using BepiPred-3.0, Epitope1D, DiscoTope-3.0, NetNGlyc-1.0, and NetO-Glyc-4.0. (3) Results: The 12,267-nt GX24 genome (GenBank: PX682047) was classified as BVDV-2b. Recombination analysis detected a putative recombination signal within the NS5A gene involving Chinese BVDV-2b and Italian BVDV-2a strains. Integrative analyses predicted conserved linear and conformational epitope clusters in the N- and C-terminal regions of the E2 protein. Spatial analysis indicated that several epitope residues may be masked by glycan shielding. (4) Conclusions: This study provides the first genomic evidence of a BVDV-2b isolate from dairy buffalo in China, suggesting that BVDV-2b may be present in this population. The putative recombination signal and antigenic characteristics offer valuable insights for the development of diagnostics and vaccine design in the future. Full article

Direct-acting antivirals (DAAs) cure most chronic hepatitis C virus (HCV) infections, yet whether the gut microbiota returns toward a healthy state after viral clearance remains uncertain. We systematically reviewed DAA-era adult HCV studies using sequencing-based fecal microbiota assessment (PROSPERO CRD420261374682). Longitudinal alpha-diversity change was pooled by REML random-effects meta-analysis with Hartung–Knapp adjustment, and compositional/functional findings were synthesized narratively. Seven studies met qualitative criteria and five longitudinal reports were extractable. Because participant overlap between two Thai reports could not be excluded, the primary conservative non-overlap analysis of four reports (180 paired observations) gave Hedges’ g = 0.13 (95% CI −0.53 to 0.80; I² ≈ 89%); the five-report sensitivity estimate was directionally positive but imprecise (g = 0.35, 95% CI −0.38 to 1.07). Recovery concentrated in richness (Chao1), whereas evenness-weighted diversity (Shannon, Hill) barely moved; beneficial taxa such as Faecalibacterium and Blautia increased after SVR. These findings are consistent with uneven, richness-led microbial recovery, but the overall certainty of the pooled evidence is very low (GRADE); functional and clinical recovery remain insufficiently characterized and undemonstrated. Full article

Bovine coronavirus (BCoV) is a key pathogen causing calf diarrhea and bovine respiratory diseases, bringing sustained economic losses to the cattle industry. As an RNA virus, BCoV possesses high mutation and recombination capacities, leading to prominent genomic genetic diversity. The genome contains hypervariable and conserved regions, with the S (especially S1), HE and Open Reading Frame (ORF4) genes serving as major variation hotspots linked to viral antigenicity, tissue tropism shift and immune evasion. Host immune pressure drives strong positive selection on S protein antigenic variation. This review discusses existing research limitations and proposes future directions including genomic surveillance, reverse genetics verification and broad-spectrum vaccine development to support BCoV prevention and control. Full article

Sweet potato (Ipomoea batatas (L.) Lam) is an important global food crop, but its production is threatened by numerous viral pathogens. More than 30 RNA and DNA viruses have been reported worldwide, making rapid and accurate detection essential for disease management, epidemiological surveillance, germplasm exchange, and resistance breeding. Although previous reviews have addressed sweet potato viruses and individual diagnostic methods, a comprehensive synthesis of emerging molecular technologies remains limited. This review addresses that gap by critically integrating recent advances from PCR-based and isothermal assays to high-throughput sequencing, CRISPR-based diagnostics, biosensors, nanotechnology, and artificial intelligence-driven detection platforms. Conventional approaches, including symptom observation, biological indexing, electron microscopy, and ELISA, have contributed to early virus identification but often lack the sensitivity, specificity, and speed needed for modern diagnostics. Molecular and isothermal techniques have substantially improved detection accuracy and enabled rapid identification and field-deployable diagnostics of diverse and mixed infections, while sequencing, CRISPR, biosensors, and AI-based platforms offer greater capacity for detecting novel and emerging viruses. This review discusses the comparative evaluation of molecular technologies for sweet potato virus detection in terms of diagnostic performance, cost-effectiveness, speed, and suitability for both laboratory and field applications, while highlighting future priorities for next-generation virus diagnostics. Integrating portable and high-throughput diagnostic platforms will strengthen virus surveillance, support virus-free planting material production, and promote sustainable sweet potato production worldwide. Full article

SARS-CoV-2 relies on a virus-encoded RNA capping pathway to produce 5′ cap structures that are essential for mRNA stability, efficient translation, and evasion of host innate immune surveillance. Within this pathway, nonstructural protein 14 (nsp14) catalyzes N7 methylation of the guanine cap, a key step that converts the cap core into a functional Cap-0 structure and enables subsequent maturation. Owing to its essential role in viral replication and its high conservation across coronaviruses, nsp14 has emerged as an attractive antiviral target. Recent structural and biochemical studies have elucidated the architecture of the nsp14 N7-methyltransferase domain, revealing an S-adenosyl-L-methionine (SAM)-dependent fold with a defined cofactor-binding site and an adjacent cap-binding pocket that orients the RNA substrate for methyl transfer. These insights have guided the development of diverse inhibitor classes, including SAM-competitive analogs, bisubstrate-like compounds, and non-nucleoside inhibitors identified through screening approaches. While early SAM-like inhibitors demonstrated target tractability, their therapeutic potential has been limited by challenges in selectivity and cellular permeability. More recent inhibitors that target the cap-binding pocket or exploit product-assisted ternary complex mechanisms highlight alternative strategies for achieving improved potency and specificity. Despite these advances, current structural models rely on truncated RNA substrates and isolated protein constructs, which may not fully capture the native catalytic environment. Future efforts to resolve nsp14 within the replication–transcription complex and develop novel inhibition strategies will be critical for advancing mechanistic understanding and antiviral development. Full article

Machine learning is increasingly used to relate molecular descriptors, formulation variables, and biophysical measurements to aggregation, viscosity, solubility, and shelf-life outcomes. The evidence is promising but uneven. Most published datasets contain tens to a few hundred antibodies, use different assays and endpoint definitions, and rely mainly on internal validation. Direct evidence for bispecific antibodies, antibody–drug conjugates, mRNA–lipid nanoparticles, and viral vectors remains limited. This structured critical review evaluates what current models can support, how data and validation choices shape reported performance, and where claims exceed the available evidence. We searched PubMed through 30 June 2026 using predefined queries for machine learning, biopharmaceutical formulation, colloidal stability, advanced modalities, and shelf-life modelling. Studies were assessed by molecular diversity, formulation coverage, endpoint quality, split strategy, external validation, and decision relevance. The strongest current use cases are early antibody developability screening, high-concentration viscosity classification, formulation ranking within a defined experimental domain, and image-based particle classification. Long-term shelf-life prediction may benefit from hybrid kinetic and machine learning models, but real-time confirmation remains necessary. Progress will depend less on larger algorithms than on better labels, molecule-level validation, shared reference datasets, and clear uncertainty reporting. Full article

Ticks are vectors of bacterial, viral, and protozoan pathogens and represent a growing public health concern in the United States and worldwide. In California, vector surveillance has largely focused on Ixodes pacificus, the major vector of the spirochete, Borrelia burgdorferi. However, the presence of multiple medically important Dermacentor species may harbor additional, understudied pathogens. To address this gap, broad pathogen screening was conducted on ticks collected from Siskiyou, Humboldt, Trinity, and Mendocino counties in Northern California, using multiplex quantitative PCR targeting 15 known tick-borne pathogens in the USA. A total of 376 adult ticks were collected in total, comprising I. pacificus, D. similis, D. andersoni, and D. occidentalis, from vegetation and animals between 2023 and 2024. Five established bacterial pathogens, Anaplasma phagocytophilum, B. burgdorferi, B. miyamotoi, Rickettsia monacensis, and R. rhipicephali were detected. Additionally, a genetically divergent Rickettsia-like sequence was detected in one I. pacificus sample that did not match any previously described species in phylogenetic analyses. Furthermore, a short DNA fragment highly similar to the Colorado tick-fever-virus VP12 gene was detected in D. similis. These findings suggest pathogen diversity across multiple tick species in Northern California, including evidence of co-infections, and the detection of potentially novel or poorly characterized microorganisms. Full article