Viruses-Basel最新文献

Background: Human noroviruses are the leading cause of foodborne gastroenteritis worldwide. Accumulating evidence suggests that food matrices containing fucosylated or histo-blood group antigen (HBGA)-like glycans may facilitate viral attachment and persistence, yet the molecular mechanisms underlying these interactions remain unclear.

Methods: In this study, we performed a comparative computational analysis of norovirus-glycan interactions by integrating AlphaFold3-based structure prediction, molecular docking, and molecular dynamics simulations. A total of 182 P-domain models representing all genotypes across five human norovirus genogroups (GI, GII, GIV, GVIII, and GIX) were predicted and docked with a lettuce-derived core-fucosylated hexasaccharide (H₂N₂F₂) previously identified by our group. The three complexes exhibiting the most favorable docking energies were further examined using 40 ns molecular dynamics simulations, followed by MM/GBSA binding free energy calculations and per-residue decomposition analyses.

Results: Docking results indicated that the majority of modeled P proteins were able to adopt energetically favorable interaction poses with H₂N₂F₂, with predicted binding energies ranging from -3.7 to -7.2 kcal·mol^-1. The most favorable docking energies were observed for GII.6_S9c_KC576910 (-7.2 kcal·mol^-1), GII.3_MX_U22498 (-7.1 kcal·mol^-1), and GII.4_CARGDS11182_OR700741 (-6.8 kcal·mol^-1). Molecular dynamics simulations suggested stable ligand engagement within canonical HBGA-binding pockets, with recurrent residues such as Asp374, Gln393, and Arg345 contributing to electrostatic and hydrophobic interactions, consistent with previously reported HBGA-binding motifs. MM/GBSA analyses revealed comparatively favorable binding tendencies among these complexes, particularly for globally prevalent genotypes including GII.3, GII.4, and GII.6.

Conclusions: This work provides a large-scale structural and energetic assessment of the potential interactions between a naturally occurring lettuce-derived fucosylated hexasaccharide and human norovirus P domains. The results support the notion that core-fucosylated food-associated glycans can serve as interaction partners for diverse norovirus genotypes and offer comparative molecular insights into glycan recognition patterns relevant to foodborne transmission. The integrative AlphaFold3-docking-dynamics framework presented here may facilitate future investigations of virus-glycan interactions within food matrices.

The rapid evolution of SARS-CoV-2, particularly the emergence of Omicron subvariants, has significantly reduced the efficacy of existing vaccines and monoclonal antibodies. This study investigates the phenomenon of immune imprinting by comparing two phage display antibody libraries derived from early 2020 wild-type SARS-CoV-2 convalescents (WT-AbLib) and early 2023 Omicron convalescents (Omi-AbLib). The capacity and diversity of both antibody libraries were systematically evaluated. The libraries were screened using BF.7 and XBB.1.5 antigens. WT-AbLib showed markedly reduced diversity after Omicron antigen selection, with dominant clones shifting from IGHV3-66-class broadly neutralizing antibodies (bnAbs) targeting the receptor-binding motif to IGHV1-46-class broadly non-neutralizing antibodies targeting conserved lateral receptor-binding domain (RBD) sites. Omi-AbLib maintained higher diversity, but dominant antibodies were also non-neutralizing and targeted the same conserved lateral region. These findings suggest that immune imprinting drives the dominance of broadly non-neutralizing antibodies following Omicron breakthrough or reinfection. This phenomenon provides a mechanistic explanation for persistent viral evasion and recurrent infection, and highlights major challenges for the development of next-generation broadly neutralizing therapeutics.

Viral RNA structure plays a critical regulatory role in viral replication, serving as a dual-purpose mechanism for encoding genetic information and controlling biological processes. However, these structural elements also serve as pathogen-associated molecular patterns (PAMPs), which are recognized by pattern recognition receptors (PRRs) of the host innate immune system. This review discusses the complex and poorly understood relationship between viral RNA structure and recognition of RNA by PRRs, specifically focusing on Toll-like receptor 3 (TLR3) and Retinoic acid-inducible gene I (RIG-I). While current interaction models rely upon data generated from use of synthetic ligands such as poly(I:C) or perfectly base-paired double-stranded RNA stems, this review highlights significant gaps in our understanding of how PRRs recognize naturally occurring viral RNAs that fold into highly complex three-dimensional structures. Furthermore, we explore how viral evolution and nucleotide variations, such as those observed in influenza viruses, can drastically alter local and distal RNA structure, potentially impacting immune detection. We conclude that moving beyond synthetic models to understand natural RNA structural dynamics is essential for elucidating the mechanisms of viral immune evasion and pathogenesis.

Respiratory syncytial virus (RSV) is among leading global causes of lower respiratory tract infections, yet data from Russia and other states of the Former Soviet Union (FSU) remain fragmented and structurally inconsistent. This systematic review aims to map and synthesize existing evidence on RSV epidemiology and genotypic distribution across the FSU. Published studies from eLIBRARY and PubMed databases queried for RSV prevalence data, together with public health surveillance datasets, were used to summarize RSV prevalence research across eight FSU countries. Random-effects meta-analysis across age strata showed high prevalence in children before 6 (21%) and a progressive decline with age, which is in agreement with global data. Prevalence estimates showed a high degree of variability partially explained by study scope and clinical presentation. We observed COVID-19-related seasonal disruptions of RSV seasonality, followed by gradual post-pandemic stabilization. Genotypic data reflects global trends with two cosmopolitan clades, A.D and B.D, and their descendants, dominating in the region. The review is limited by uneven geographical and temporal coverage, and scarce data on adults. The review provides the first integrated summary of RSV epidemiology across the FSU and underscores the need for expanded regional surveillance and genomic reporting.

Host-virus relationships regulate every phase of viral infection and critically influence course of illness and the effectiveness of treatment. Viruses utilize host receptors, intracellular trafficking routes, metabolic programs, and immunological signaling networks to introduce infection, while host cells use innate and adaptive immune responses that both limit viral replication and, in certain situations, cause tissue damage. Given the fast viral evolution and drug resistance linked to virus-directed therapy, there is growing proof that these host-dependent mechanisms are appealing and underutilized targets for antiviral treatment. Recent developments in single-cell technology, proteomics, and functional genomics have made it possible to systematically identify host dependency and restriction factors shared by different viral families, exposing common molecular vulnerabilities that might be targeted therapeutically. This review integrates current knowledge of virus-host interplay via a translational lens, highlighting processes that directly guide the formation of host-directed antivirals and immune-regulating treatments. We emphasize host processes involved in viral entry, replication, and immune signaling that have shown therapeutic significance, while illustrating the difficulties of balancing antiviral effectiveness with immunopathology. By framing host-virus interactions through a therapeutic lens, this review attempts to offer a targeted and translationally relevant viewpoint for next-generation antiviral research.

Protoparvoviruses are highly contagious pathogens that cause severe, often fatal diseases in both domestic and wild carnivores. Golden jackal (Canis aureus) populations have experienced expansion in recent years, increasingly occupying urban and peri-urban areas. Despite this, they remain largely overlooked in scientific research. This study aimed to detect and characterise Protoparvovirus carnivoran1 circulating in a golden jackal population in Croatia and to assess their role in the epidemiology of parvovirus infections in companion animals. Small intestines from 55 jackals hunted in 2024 and 2025 were tested for Protoparvovirus carnivoran1 using real-time PCR. Positive samples were found across all sampling sites, with an overall positivity rate of 40%. Based on characteristic amino acid residues within the VP2 protein, the viruses detected in jackals were classified as feline panleukopenia virus (FPV). Phylogenetic analysis of the VP2 protein demonstrated considerable genetic diversity among strains circulating in Croatia. Additionally, a distinct group was identified, shared exclusively by Croatian domestic cats and golden jackals. Amino acid analysis revealed the novel A91T mutation, found only in jackals, and the E411Q mutation, unique to Croatian FPV strains. Structural modelling of the VP2 protein indicates that the observed mutations are located on the protein surface, within the antibody-binding site. These findings highlight the potential role of wild carnivores in parvovirus epidemiology and underscore the importance of including them in future surveillance and research efforts.

Reticuloendotheliosis virus (REV) is an immunosuppressive virus in poultry that can cause acute reticular neoplasms, chronic lymphoid tumors, stunting syndrome, and secondary infections. In many countries, the lack of effective vaccines has resulted in a high prevalence of REV infections and substantial economic losses. Enzyme-linked immunosorbent assay (ELISA)-based antibody detection is an important tool for monitoring the REV prevalence in poultry farms. ELISA coating antigens generally consist of either whole virus or viral protein; however, most commercially available REV antibody ELISA detection kits use whole virus as the coating antigen, which limits their applicability in certain diagnostic and research settings. In this study, the gp90 protein from a dominant REV strain was expressed and purified using 293F suspension cell eukaryotic expression system. Using recombinant gp90 protein as the coating antigen, an indirect ELISA for detecting gp90 antibodies (gp90-ELISA) was developed. After optimization, the optimal conditions were as follows: coating antigen concentration of 4 µg/mL with overnight incubation at 4 °C; blocking with 5% skim milk at 37 °C for 1.5 h; serum dilution of 1:200 with incubation at 37 °C for 45 min; secondary antibody dilution of 1:1000 with incubation at 37 °C for 30 min; and color development using TMB substrate at room temperature in the dark for 10 min. The cut-off value was defined as an OD₄₅₀ ≥ 0.22 for positive samples and <0.22 for negative samples. The developed gp90-ELISA specifically detected REV-positive sera at a maximum serum dilution ratio of 1:3200. Intra- and inter-assay variation coefficients were ≤10%, indicating that the gp90-ELISA had good specificity, sensitivity, and reproducibility. Laboratory serum testing showed that the gp90-ELISA successfully detected sera from chickens immunized with the gp90 protein or infected with REV. Furthermore, analysis of clinical serum samples demonstrated 100% concordance between the gp90-ELISA results and a commercial whole-virus-coated ELISA kit. These results indicate that the gp90-ELISA is a reliable supplementary method to whole-virus-coated ELISA and has potential utility in disease surveillance and evaluation of immune responses.

Objective: To better define potential executive function difficulties in individuals living with HIV but not clinically identified as having HAND, with and without mild to moderate cocaine dependence (CD), our cross-sectional study examined executive function performance on the Stroop Color-Word Test (Stroop) and the Trail Making Test (TMT) in four groups stratified by HIV and CD status.

Method: We recruited 101 participants (26 HIV+/CD+; 18 HIV+/CD-; 30 HIV-/CD+; 27 HIV-/CD-). We utilized a 2 (HIV: yes/no) × 2 (Cocaine: yes/no) MANCOVA while controlling for age and premorbid intelligence on the Stroop trials (i.e., color-naming, word-reading, interference), and TMT-A and TMT-B z-scores, number of errors, and the B/A ratio.

Results: HIV was associated with significantly slower performance on the Stroop Interference (p = 0.012, η² = 0.064). CD showed a trend towards slower performance on interference trials (p = 0.061, η² = 0.037) and was associated with significantly more errors on the Stroop Word-Reading (p = 0.028, η² = 0.050) and Interference trials (p = 0.046, η² = 0.041), suggestive of difficulties with inhibitory control and written language processing. There were no significant HIV × Cocaine interactions.

Conclusions: Our results suggest HIV without clinically identified cognitive impairment and CD are associated with distinct and potentially overlapping executive functioning deficits, particularly for measures of inhibitory control. Notably, CD showed trend-level slowing on Stroop Interference performance, suggesting partial overlap with HIV effects. Clarifying the specific cognitive processes impacted by HIV and CD can help guide tailored interventions to improve functional outcomes in these populations.

Human non-polio enteroviruses (NPEVs) cause a plethora of infections in humans, ranging from mild to severe neurological diseases including aseptic meningitis. NPEVs are the leading cause of aseptic meningitis in both children and adults worldwide. In Russia, reports of NPEV infections have surged, especially in the post-COVID era starting in 2022, with elevated infection rates into 2023. A comprehensive examination of the whole genome is crucial for understanding the evolution of NPEV genes and for predicting potential outbreaks. This study focused on identifying the circulating NPEV strains in the Ural Federal District and Western Siberia, using Sanger sequencing and next-generation sequencing (NGS) methodologies. Biological samples were collected from (n = 225) patients diagnosed with aseptic meningitis. Bioinformatics analysis targeted the nucleotide sequences of the major capsid protein (partial VP1) gene fragment, and the assembly of whole NPEV genomes. A total of 159 NPEVs were characterized, representing 70.7% of the collected samples. The main capsid variants forming the predominant genotypic profile included E30 (n = 39, 24.3%), E6 (n = 31, 19.3%), and CVA9 (n = 25, 15.6%). Using NGS, we successfully assembled 13 whole genomes for E6, E30, EV-B80, CVA9, CVB5, E11, and EV-A71 and 3 partial genomes for E6 and EV-B87. This molecular-genetic analysis provides contemporary insights into the genotypic composition, circulation patterns, and evolutionary dynamics of the dominant NPEV associated with aseptic meningitis in the Ural Federal District and Western Siberia. The laboratory-based monitoring and epidemiological surveillance for genetic changes and evolutionary studies are important for improving prevention and healthcare.

Astroviruses are non-enveloped, positive-sense single-stranded RNA viruses known to infect various mammals and birds, including humans, often causing gastrointestinal disorders. In recent years, astroviruses have also been linked to neurological and respiratory diseases across several species, including ruminants, mink, deer, and other mammals. Notably, astrovirus infections in goats have been documented in countries such as Switzerland and China, where novel genotypes have been identified in fecal samples. However, their role in the context of disease remains unclear, and reports focusing solely on goat astrovirus in the United States have not been published. A necropsy case of a Boer goat kid with a history of diarrhea was submitted for investigation following death in January 2025. Fresh tissues were received and used for histopathology and enteric pathogen testing, including parasitic, bacterial, and viral workups. Metagenomic-based next-generation sequencing (mNGS) was also applied for this case. Histological examination revealed severe necrotizing enterocolitis. The small intestine exhibited epithelial ulcerations, villus atrophy, hyperplastic and dilated crypts with necrotic debris, few intraenterocytic coccidian parasites, and increased inflammatory cells in the lamina propria. The large intestine showed similar findings with pleomorphic crypt enterocytes. Standard enteric pathogen tests were negative except for aerobic culture that identified Escherichia.coli and Enterococcus hirae. mNGS and bioinformatic analysis identified a novel astrovirus in the intestinal content that showed the highest nucleotide identity (86%) to the sheep strain Mamastrovirus 13 sheep/HA3 from China based on BLAST analysis. Phylogenetic analysis indicated that the newly identified caprine astrovirus IL90175 clustered with astrovirus strains from small ruminants in Asia and Europe. This research reports the discovery, histopathologic features, and genetic characteristics of a gastrointestinal disease-causing astrovirus in a goat kid, which had not been previously described in the United States.