2026-03-04
Sare Madani, Kumars Amini, Seyed Amir Hassan Habibi, Mohammad Hassan Shahhosseiny, Taher Mohammadian
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.
DOI: 10.3389/av.2026.144992025-12-01
Zahra Yazdani, Alireza Rafiei, Ali Yousefiyan, Keyvan Jaberi
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.
DOI: 10.3389/av.2025.146592025-07-07
Adriana Manuka, Irsida Mehmeti, Antonia Radaelli, Eduart Hashorva, Carlo Zanotto, Carlo De Giuli Morghen
Due to the successful eradication of smallpox worldwide and the cessation of smallpox vaccination campaign in 1980, the human population seems to be more susceptible to poxvirus infection. In the last years, an increased detection of zoonotic orthopoxviruses (OPXVs) has also been observed. In particular, in the past 50 years, a high incidence of monkeypox virus (MPXV) disease (MPOX) in both Central and Western Africa was reported. MPXV is not as lethal as variola virus (VARV), the etiological agent of smallpox, but it represents a threat to public health. The global events of MPOX in May 2022, and the ongoing outbreaks in Central and Western Africa in August 2024, have prompted the World Health Organization (WHO) to declare MPXV a Public Health Emergency of International Concern. Preventive vaccination remains the most effective control against MPXV. Smallpox vaccines of the second and third generations have been suggested for high-risk groups, in spite of several limitations, such as some adverse events, reduced immunogenicity, and manufacturing issues. The emerging threat of MPXV highlights the urgent need for the development of vaccines that can effectively control MPOX and potentially prevent diseases caused by other related OPXVs. Our study aims at introducing basic information on the biology of poxviruses, and on factors that may contribute to the reemergence of zoonotic poxviruses. It also summarizes the evolution of vaccinia-based vaccines and strategies that may control and prevent future outbreaks.
DOI: 10.3389/av.2025.145972025-04-08
Jana Kemenczeiová, Peter Alaxin, Lukáš Predajňa, Zdeno Šubr, Miroslav Glasa, Adam Achs
Grapevine yellow speckle viroid 1 (GYSVd-1) is a widespread subviral pathogen affecting grapevine (Vitis vinifera L.), with potential implications for viticulture. This study investigates the prevalence, genetic variability, intrahost population polymorphism and secondary RNA structure of GYSVd-1 in Slovakia, where its molecular characteristics have been largely unexplored. Leaf samples from 49 grapevine plants across western and southern Slovakia were analyzed using RT-PCR, followed by sequencing and phylogenetic analyses. GYSVd-1 was detected in 73% of the samples, demonstrating high prevalence rates across vineyards in Slovakia. Sequence analysis revealed a high degree of genetic similarity among Slovak isolates, with nucleotide identity ranging from 96.2% to 100%, consistent with low variability reported globally. Phylogenetic analyses showed no specific grouping of Slovak isolates. Intrahost variability, assessed via subcloning of RT-PCR products, demonstrated the presence of random mutations among viroid clones, consistent with quasispecies nature of viroids in their hosts. These findings suggest that both interhost and intrahost viroid populations evolve under similar pressures to maintain structural stability essential for viroid function. Secondary RNA structure analysis of Slovak GYSVd-1 isolates revealed that all unambiguous sequences exhibited the characteristic rod-like conformation. In contrast, a significant proportion of sequences from mixed populations failed to form proper rod-like structures, suggesting that these variants may lack biological viability. Overall, this study unveils the prevalence of GYSVd-1 in Slovak vineyards and provides valuable insights to guide future phylogenetic studies and structural analyses of viroids.
DOI: 10.3389/av.2025.143612025-04-03
Hyeop Jin, Ye Rae Cho, Yong Tae Jung
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an enveloped, single-stranded RNA virus, is causative of coronavirus disease 2019 (COVID-19). The viral entry process is facilitated by the highly antigenic spike protein of SARS-CoV-2, which binds to the angiotensin-converting enzyme 2 (ACE2) receptor. However, research involving live SARS-CoV-2 is limited to biosafety level (BSL)-3 facilities, hindering the progress in vaccine and therapeutic development. Pseudotyped viruses have emerged as valuable tools for studying entry inhibitors, fusion inhibitors, and neutralizing assays in BSL-2 facilities. Several modifications to the spike protein have been identified to enhance the yield of pseudotyped viruses. Notably, the removal of the last 19 amino acids from the spike protein and the D614G modification have been shown to increase pseudovirus titers. In this study, we aimed to identify an effective expression vector for pseudotyping by inserting SARS-CoV-2 S Δ19 into the intron-containing pcDNA3.1 vector. The inclusion of the β-globin intron sequence led to a significant augmentation in spike protein expression and a threefold improvement in pseudotyped virus production. Furthermore, we examined whether the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) could enhance spike protein expression by subcloning the spike protein gene into a lentiviral vector containing WPRE. Our results demonstrated that vectors containing the WPRE exhibited increased spike protein expression compared to vectors lacking the WPRE in HEK293-hACE2 cells. This study demonstrates that the inclusion of a β-globin intron and WPRE enhances the production of SARS-CoV-2 spike protein pseudotyped lentiviruses, a valuable tool for COVID-19 research.
DOI: 10.3389/av.2025.142622025-01-10
Dongjin Choi, Hyerin Park, Seungwoo Baek, Myeung Seok Choi, Sylvain Legay, Gea Guerriero, Jean-François Hausman, Yoonsoo Hahn
Some plant RNA viruses in the family Betaflexiviridae encode a nucleic acid-binding protein (NABP) that facilitates infection by suppressing the host RNA silencing response. Previously, no members of the genus Tepovirus within this family were known to possess a NABP homolog. In this study, we identified the genome sequences of 21 novel Betaflexiviridae viruses: 17 represent new members of Tepovirus, and four may be founding members of a new genus closely related to the genus Vitivirus. Notably, five of these newly identified tepoviruses contain a NABP-like open reading frame (ORF). Sequence comparison and phylogenetic analysis of NABP homologs suggest these tepoviruses independently acquired a NABP-like ORF from diverse sources. The identification of 17 novel viruses substantially enhances our understanding of the genetic diversity within the genus Tepovirus. This study further highlights the role of recombination in the genome evolution and diversity of Betaflexiviridae.
DOI: 10.3389/av.2024.139522024-09-25
Michaela Pellerova, Katarina Albertova, Vanesa Simkova, Maria Borsanyiova, Brigita Benkoova, Renata Kissova, Katarina Pastuchova, Sisko Tauriainen, Jochem M. D. Galama, Shubhada Bopegamage
Enterovirus (EV) infections occur frequently in humans. In some geographical areas they are more common. These viruses cause diseases with varying degrees of severity, from a simple respiratory tract infection to severe diseases. Since EVs include more than 70 serotypes currently circulating in the population, a methodology that detects most of them is needed. ELISA is a rapid, sensitive, and economical diagnostic method for the identification of EV serotypes and can also be used as a retrospective diagnostic tool or in the investigation of outbreaks of infection. Commercial EV-ELISAs often appear and gradually disappear from the market supply. We have used the KTL-510 peptide, a synthetic viral protein of poliovirus VP1, as an antigen in a peptide-based ELISA for the detection of a broader spectrum of anti-EV antibodies. We aimed to design, optimize, and standardize this in-house ELISA with the peptide, and implement the method for routine detection of anti-EV IgG in human sera. For determining the cut-off value, we used 100 patients’ sera which were previously tested negative for IgG antibodies against EVs using a commercial ELISA kit available. We monitored patients’ sera samples sent for serological testing of anti-coxsackievirus antibodies to the National Reference Center for the Identification of Enteric Viruses between 2018–2022. These serum samples were examined using a standard virus neutralization test as well as the newly developed ELISA method.
DOI: 10.3389/av.2024.12739