Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by dopaminergic neuronal loss, motor dysfunction, and a range of non-motor symptoms. While the etiology of PD remains elusive, emerging evidence suggests a significant role for latent herpesvirus infections in its pathogenesis. This study investigates the prevalence and viral loads of herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in PD patients compared to age- and sex-matched healthy controls. Using multiplex PCR and quantitative PCR, we demonstrate a higher prevalence of HSV-1 and VZV in PD patients, with their viral loads correlating significantly with disease severity and elevated levels of interleukin-6 (IL-6), a marker of systemic inflammation. Our findings reveal that active herpesvirus infections exacerbate neuroinflammation, potentially accelerating dopaminergic neurodegeneration. While CMV and HSV-2 showed no significant differences, the co-infection of HSV-1 and VZV was associated with more severe non-motor symptoms, such as cognitive decline and depression. These results underscore the potential of targeting herpesvirus reactivation and associated inflammation as a novel therapeutic approach for managing PD. Antiviral therapies and vaccination strategies, particularly for HSV-1 and VZV, warrant further investigation to mitigate PD progression.
A wide range of species contract a haemorrhagic disease caused by Bluetongue virus (BTV), which is transmitted by hematophagous midges of Culicoides species. The virus shows variation in its pathogenicity and virulence between the mammalian and insect hosts, implicating the role of host proteins in its life cycle. NS3, a versatile protein of BTV, performs a major role in viral egress by acting as perforin. Multifunctional roles of NS3 have also been reported in viral pathogenesis, but there are critical gaps in explaining the exact mechanisms of its crosstalk with the host, creating the space for NS3-host interaction studies. In this study, we report the screening of host proteins interacting with NS3 protein of BTV using yeast-two hybrid (Y2H) assay. An ovine cDNA library derived from sheep lung and the truncated NS3 (NS3t) bait were constructed and evaluated for competency parameters. Following stringent screening, 37 putative host interaction partners were identified, of which eight proteins were selected for validation using alternative yeast-based assays; seven of these interactions were confirmed as positive. NAP1L1/NS3 interaction was further verified with GST pull-down, co-immunoprecipitation and mammalian two-hybrid assays. The results indicate that NAP1L1, a protein involved in nucleosome assembly and cell cycle regulation, interacts with the BTV NS3 protein.
Introduction COVID-19 infection causes significant changes in certain hematological markers and increases inflammatory severity, such as NLR, LMR, PLR, and Ferritin. In contrast, the Pfizer-BNT162b2 mRNA-based vaccine does not induce high levels of inflammation.Methods A prospective cohort study, conducted at the University of Diyala from January 2022 to January 2023, assessed the immune response to the Pfizer-BNT162b2 mRNA vaccine in 45 healthy, unvaccinated medical students aged 18 to 23. The study evaluated Complete Blood Count, proinflammatory cytokines, ferritin, and anti-IgG antibodies at the time of the second dose of vaccination and 4 weeks after the second dose of the vaccine. Biomarkers were analyzed using CBC instrumentation, ELISA, and Cobas e411 assays, with ethical approval granted for the study.Results Hemoglobin levels remained stable, while red blood cell (RBC) volume and RDW-CV significantly decreased. RBC indices (MCH, MCHC, HCT) increased, and total leukocyte counts slightly declined with a notable granulocyte rise. The platelet count remained stable; however, the plateletcrit decreased, while MPV and PDW increased. NLR and PLR levels increased significantly, whereas LMR levels decreased. No significant change occurred in PHR, SIRI, or AIRI. Inflammatory markers (TNF-alpha, ferritin, CD256/APRIL) and anti-spike IgG levels significantly increased after 1 month. Anti-spike IgG levels showed no strong correlations with SIRI, AIRI, PLR, PHR, or MLR, though significant intercorrelations were found among hematological ratios (e.g., PLR with PHR, SIRI, AIRI; LMR with AIRI).Conclusion Pfizer-BNT162b2 mRNA vaccine had a significant impact on the organized redistribution of immune cells.
In this study, a combination of bioinformatics tools was employed to design a multi-epitope peptide-based vaccine against the Crimean-Congo hemorrhagic fever virus (CCHFV). The vaccine construct incorporates immunodominant epitopes derived from the envelopment polyprotein and the RNA-dependent RNA polymerase (L protein) of the Nigerian strain of CCHFV. Two potent adjuvants were included in the design to enhance immunogenicity. The structural and immunological characteristics of the vaccine were thoroughly evaluated. Both secondary and tertiary (3D) structure predictions were performed. The results indicated that the vaccine is antigenic and non-allergenic. Three-dimensional B-cell epitope prediction revealed that 108 residues within the construct are conformational (discontinuous) B-cell epitopes. Molecular docking and dynamic simulations with Toll-like receptors (TLRs) 2, 3, and 8 demonstrated stable interactions between the vaccine and these immune receptors. In silico cloning and mRNA stability analyses suggested that the construct is suitable for expression in Escherichia coli. Additionally, immune simulation results indicated that the vaccine could elicit a robust adaptive immune response following administration. Overall, the designed multi-epitope vaccine candidate demonstrates high structural quality and favorable immunological properties, supporting its potential to induce protective immunity against CCHFV.
The family Amalgaviridae comprises monopartite double-stranded RNA viruses that encode two overlapping open reading frames (ORFs), ORF1 and ORF2. A programmed ribosomal frameshifting (PRF) mechanism facilitates the translation of an ORF1+2p fusion protein. Among the three recognized genera (Amalgavirus, Unirnavirus, and Zybavirus), Zybavirus remains poorly characterized, with only one approved species, Zygosaccharomyces bailii virus Z (ZbV-Z), and a few unclassified proposed members. In this study, we identified four novel zybavirus-like viral genome sequences, tentatively named Zygosaccharomyces bailii virus Z2 (ZbV-Z2), Cryptops hortensis-associated virus Z1 (ChaV-Z1), Drosophila suzukii-associated virus Z1 (DsaV-Z1), and Sand Creek Marshes virus Z1 (SCMV-Z1), from publicly available transcriptome datasets. Phylogenetic analysis placed ZbV-Z2, ChaV-Z1, and DsaV-Z1 in a well-supported clade with ZbV-Z and Xisha Islands zybavirus, supporting their classification within Zybavirus. SCMV-Z1 clustered with seven known viruses in a distinct lineage, which may represent a novel genus within the family Amalgaviridae. Comparative analysis of PRF sites in members of Zybavirus, Amalgavirus, and related clades revealed that UUU_CNN may represent a broader and ancestral consensus +1 PRF motif in this group of viruses. Our study highlights the utility of mining public transcriptome data for novel viral genome discovery and contributes to the refinement of both taxonomic classification and conserved genomic features within this viral family.
