Viruses-Basel最新文献

In the original publication [...].

Background: Developing an effective vaccine is crucial for the prevention and control of AIDS. Viral vector-based vaccines, particularly those utilizing homologous or heterologous prime-boost strategies, represent an important direction in current HIV vaccine research.

Methods: In this study, replication-defective chimeric adenovirus Ad5F35 and modified vaccinia virus Ankara (rMVA) vector vaccines expressing the HIV-1 AEgp145 were successfully constructed, designated as Ad5F35-AEgp145 and rMVA-AEgp145, respectively. Sixty BALB/c mice were randomly divided into three groups: Ad5F35 alone, rMVA prime/Ad5F35 boost, and PBS control. The mice were immunized intramuscularly at weeks 0 and 3, and humoral and cellular immune responses were assessed at 4, 8, 12, and 16 weeks after the initial immunization.

Results: The homologous Ad5F35 and heterologous rMVA/Ad5F35 vaccination regimens elicited comparable levels of HIV Env-specific cellular immune responses, peaking at 2100 ± 222 SFCs/million splenocytes and 2200 ± 619 SFCs/million splenocytes, respectively (p > 0.05). Compared to the heterologous regimen, the homologous Ad5F35 regimen induced significantly higher levels of gp120-binding antibodies at weeks 4 and 8 post-initial immunization, with geometric mean titers of 1:25,600 ± 7011 versus 1:1280 ± 150.7 and 1:10,240 ± 4048 versus 1:2560 ± 391.9, respectively. Furthermore, neutralizing activity at week 8 was significantly higher in the homologous group, with a 50% neutralization titers of 1:45 compared to 1:12 in the heterologous group (p < 0.01).

Conclusion: This study demonstrates that the Ad5F35-AEgp145 vaccine, whether administered alone or in combination with rMVA-AEgp145, effectively induces strong and comparable cellular immune responses targeting HIV-1 Env in mice. While both regimens are effective, homologous immunization elicits moderately higher levels of antibody responses. These findings provide an important foundation for the further investigation of vector-based HIV vaccine formulations.

In 2020, a dairy farm in northwest Germany reported several cows with severe respiratory disease, fever, and reduced milk production. Multiple direct and indirect diagnostic methods were used to identify the cause of the disease. However, the pathogens detected could not be correlated with the severity of the clinical symptoms, so further diagnostic steps were taken. Blood and nasal swab samples were examined using next-generation sequencing (NGS) as part of a metagenomic analysis. For the first time in Germany, Hepacivirus bovis genotype 2 was detected. Real-time RT-PCR assays confirmed the presence of BovHepV genotypes 1 and 2 in the herd between 2020 and 2023. Analyses of complete and partial genome sequences demonstrated the presence of different virus variants in the herd over several years. In addition, the sequence data indicated that cattle can be reinfected with viruses belonging either to different BovHepV subtypes or to the same subtype. Although no direct link could be established between the detection of bovine hepaciviruses and the observed clinical symptoms, the PCR and sequence data obtained provide valuable insights into the epidemiology and pathogenesis of BovHepV infections.

Zinc oxide nanoparticles (ZnO NPs) have attracted growing interest in several fields, including topical biomedical applications, due to their stability, biocompatibility and therapeutic potential. In this study, chitosan (Ch), gelatin (G) and arabic gum (AG) were combined to formulate hydrogels loaded with different ZnO NP concentrations. The main aim is to assess the synergy between the properties of biopolymers and ZnO moieties in terms of antiviral activity. ZnO NPs were synthesized via co-precipitation. Hydrogels were prepared using the freeze-thaw method, and the loading of 2.5, 5 and 7.5% w/w of ZnO NPs with respect to Ch was promoted by ultrasonication. The structural, morphological, surface and thermal properties of hydrogels loaded with ZnO NPs (HZ 2.5, HZ 5 and HZ 7.5) and the control matrix (H) were characterized using FTIR spectroscopy, confirming the successful incorporation and interaction of ZnO NPs with the polymeric network. Low ZnO NP concentrations enhanced the swelling degree of the hydrogels (from 1044% to 1253%), improving their thermal stability and solubility (96 h vs. 48 h HZ 7.5 and 14 h in the case of H). This behavior could be ascribed to the aggregation of ZnO NPs with increasing amounts, which was verified through FESEM. Virucidal activity was tested against herpes simplex virus type 1 (HSV-1) and bovine coronavirus (BCoV), demonstrating a substantial enhancement when the ZnO NPs are added independently of the concentration. An almost 100% viral inhibition was recorded when the HZs were analyzed, whereas the H matrix showed an inhibition of about 40% against the same virus. Antioxidant activity was evaluated via the DPPH free radical inhibition method, revealing an improvement with the loading of NPs.

Human adenovirus type 3 (HAdV-3) in the species Mastadenovirus blackbeardi is a frequent cause of hundreds of respiratory infections in Japan, with outbreaks varying in clinical severity. Such a high frequency of cases could be due to regular migration of novel variants or persistent circulation of endemic strains. Either scenario would require different measures to ameliorate the burden on public health. We designed a new cost-effective whole-genome sequencing protocol based on tiled amplicons and nanopore sequencing to clarify the circumstances behind the frequent outbreaks. This protocol was used with clinical samples collected between 2011 and 2020 from Japanese patients with acute respiratory illness (n = 110), resulting in near whole-genome sequences (~99% length) for 105 samples with high read coverage (~262.6 ± 192 reads). Phylogenetic analysis indicated sustained circulation of endemic strains in Japan during the analyzed decade and their relation to other strains worldwide with publicly available genome sequences. However, a comparison with other Japanese HAdV-3 strains circulating since 2023 suggested the public health measures introduced during the COVID-19 pandemic (2020-2022) indirectly affected the prevalence of circulating HAdV-3 variants. Additionally, our approach enabled the detection and partial sequencing (~71% completion) of co-infecting strains from the species Mastadenovirus caesari (n = 4) in the examined samples. The detection of adenoviruses belonging to different species in the same sample highlights how our protocol enhances the distinction of circulating viruses. In conclusion, these results and the introduced protocol will enable timely characterization and clinical interventions to mitigate this virus.

In Saudi Arabia, cucurbit crops such as zucchini (Cucurbita pepo) and snake gourd (Trichosanthes cucumerina) are major vegetables and key dietary components, yet their associated viral threats remain poorly understood. We surveyed symptomatic cucurbit samples from greenhouses and open fields in the Al-Ahsa and Qatif regions. The detection methods employed included PCR, RCA, and Illumina NGS. Based on nucleotide sequence comparisons and maximum-likelihood phylogenetic analysis, we identified three viruses, i.e., TYLCV, WmCSV, and ToLCPalV, present as both single and mixed infections. Sequence analyses revealed a novel strain, TYLCV-Hasa, representing a distinct lineage of TYLCV. Analysis revealed that recombination occurred solely in the DNA-A components of the identified viruses, while DNA-B segments showed no evidence of recombination. Notably, no DNA satellites were detected, suggesting cucurbits may act as independent reservoirs of begomovirus diversity. These results provide a comprehensive genomic insight into cucurbit-infecting begomoviruses in Eastern Saudi Arabia. The discovery of TYLCV-Hasa and evidence of recombination raise concerns about the emergence of novel viral variants that could pose risks to cucurbit cultivation. The results establish a foundation for advanced molecular surveillance and breeding strategies, contributing to improved food security and supporting Saudi Arabia's Vision 2030 goals for sustainable agriculture.

Enterovirus D68 (EV-D68), a neurotropic respiratory pathogen, poses a considerable clinical threat through its link to pediatric acute flaccid myelitis (AFM) and severe respiratory illness. The possibility of recurrent epidemics, evidenced since the 2014 outbreak, remains a major concern. Genomic determinants of virulence are central to this threat. Sequence variations that affect host-receptor interactions, immune evasion, and replication efficiency serve as critical modifiers of pathogenicity. This article systematically reviews the evidence for specific genomic sites that enhance EV-D68 virulence, focusing on three critical regions: the VP1 receptor-binding site, the 2Apro/TRAF3 cleavage site, and the 3Cpro immunoregulatory region. Mutations in the VP1 receptor-binding site can alter affinity for host receptors such as sialic acid, heparan sulfate, and MFSD6, thereby shaping viral entry and tissue tropism. Alterations in the 2Apro/TRAF3 cleavage site may impair proteolytic cleavage of host TRAF3, attenuating immune evasion and reducing viral pathogenicity. Variations in the 3Cpro region affect its efficiency in cleaving host proteins involved in translation and autophagy, ultimately modulating viral replication and antiviral responses. Finally, we propose that monitoring for mutations in these key virulence determinants, particularly within the surface-exposed VP1, is essential for effective outbreak preparedness.

Introduction: Despite the impressive progress carried out in the field of biomedical sciences in recent decades, the incidence of emerging and neglected lethal viral infections mainly belonging to the Coronaviridae, Filoviridae, Arenaviridae, Bunyaviridae, and Paramyxoviridae families has considerably impaired human health. The worldwide vaccination campaign at the end of the 1970s determined the eradication of smallpox. However, the growing number of cases of diseases linked to orthopoxvirus diseases, such as the recent epidemic of monkeypox zoonosis in various countries around the world, has increased the need for knowledge of these viral pathogens. To date, there is no specific treatement for Monkeypox virus (MPXV) infection. However, several antiviral drugs used to treat Smallpox and other viral infections could also be beneficial for Monkeypox disease. In this study we report the design and synthesis of new, variously substituted benzimidazole derivatives and the evaluation of their cytotoxicity and antiviral activity against representatives of the Orthopoxvirus genus, Vaccinia Virus (VV), closely related to variola virus and MPXV.

Methods: A combination of cell-based assays and experimental techniques was used to investigate the cytotoxicity, antiviral activity, and mechanisms of action of the most interesting compound.

Results: In our study, new, variously substituted benzimidazoles showed interesting EC₅₀ values against vaccinia and MPXV and a cytotoxic profile in the high micromolar range.

Conclusions: Our work shows that the new tested benzimidazole derivatives possess appealing activity and selectivity, accompanied by low cytotoxicity. These results set a valid foundation with which to identify potent and selective anti-Poxvirus agents.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major cause of economic loss in the swine industry, and highly pathogenic variants such as NADC34-like PRRSV highlight the need for antiviral strategies that complement vaccination. In this field study, we evaluated the efficacy of AlimenWOW, a rottlerin-lipid formulation, in grower-finisher pigs under commercial conditions using AI-based respiratory monitoring. A total of 2000 pigs were assigned to four groups: AlimenWOW G1 (PRRSV-stable source farm), AlimenWOW G2 (PRRSV-unstable source farm), Control 1 (antibiotic), and Control 2 (antipyretic). Respiratory Health Status (ReHS) and a derived Clinical Cough Index (CCI = 100 - ReHS) were continuously recorded with SoundTalks^®, and oral fluid PRRSV load, serology, clinical outcomes, and productivity were assessed over 4 weeks. AlimenWOW G2 showed a marked improvement in ReHS from severely compromised baseline values to levels comparable with healthy status, while both control groups remained low; CCI was significantly lower in AlimenWOW G2 than in controls from day 14 onward (p ≤ 0.0001). AlimenWOW treatment was associated with reduced PRRSV titers in oral fluid, lower mortality and wasting rates, and improved feed conversion with lower feed costs compared with controls. These findings indicate that AlimenWOW, integrated with AI-based acoustic monitoring, can improve respiratory health and mitigate PRRSV-associated clinical and economic losses, supporting its use as a complementary tool in PRRSV control programs.

Group A rotaviruses (RVAs) remain the leading cause of acute gastroenteritis (AGE) in young children in low- and middle-income countries. In Brazil, the oral attenuated RVA vaccine (Rotarix^®), monovalent genotype G1P[8], is distributed by the national immunization program and has drastically reduced morbidity and mortality associated with RVA etiology. In this study, Rotarix^® G1P[8] was detected using specific qRT-PCR from the fecal shedding of children living in the Amazon region, and 18.3% (29/158) were positive and 75.8% (22/29) presented with AGE. The VP4 (VP8*) gene of these sheddings, submitted to Sanger nucleotide sequencing, showed an occurrence of mutations, including the silent mutation at 144C > G (one child) and the following missense mutations- 499T > C (F167L) (two children), 644G > C (C215S) (one child), and 787G > A (E263K) (one child). These mutations had no impact on the protein model structure in silico deduced from the VP4 (VP8*) mutants. The in silico protein model deduced from the VP4 (VP8*) nucleotide sequences, bound to type 1H sugar antigens (H1) and its precursor Lac-para-N-biose (LNB), had a stronger binding to the G1P[8] genotype, when compared to G3P[8]. Rotarix^® shedding was higher in HBGA secretors than in non-secretors (79.3%; 23/29). A total of 11.4% (18/158) of children with Rotarix^® G1P[8] shedding were unvaccinated, indicating the occurrence of indirect protection. Stability evidence of Rotarix^® VP4 (VP8*) spike protein from samples collected in vivo is presented.