Abstract: Glutamine is the most abundant amino acid in human plasma and tissues and plays essential roles in cellular metabolism, biosynthesis, and redox homeostasis. Beyond these canonical functions, glutamine availability and utilization have emerged as key regulators of multiple cellular stress responses, including the integrated stress response, endoplasmic reticulum stress, metabolic checkpoint signaling, and autophagy. During viral infection, host glutamine metabolism is frequently reprogrammed to meet the energetic and biosynthetic demands of viral replication, thereby inducing or reshaping glutamine-linked stress pathways. Increasing evidence indicates that these stress responses are not merely secondary consequences of infection but actively influence key stages of the viral life cycle, including viral entry, genome replication, protein synthesis, and host antiviral responses. In this review, we summarize current advances in understanding how glutamine metabolism regulates cellular stress responses in the context of both viral and non-viral infections, and how these pathways, in turn, modulate viral pathogenesis and host defense. We discuss the context-dependent roles of glutamine-linked stress signaling in either promoting viral replication or restricting infection, depending on viral species, host cell type, and metabolic conditions. Finally, we highlight emerging concepts and unresolved questions, including the potential of targeting glutamine metabolism and associated stress pathways as host-directed antiviral strategies. A deeper understanding of the interplay between glutamine metabolism, cellular stress responses, and viral infection may provide new insights into disease mechanisms and inform the development of novel therapeutic approaches.

Abstract: Percutaneous cable infection of left ventricular assist device (LVAD) patients is a significant source of morbidity, often caused by biofilm producing or multidrug resistant bacteria. We hypothesized that bacteriophage viruses can be identified from biological samples of patients with active driveline infection. Six patients with local percutaneous lead infections were enrolled. Microbiological samples were collected from the infected wound and other skin regions. The isolated viral strains and phages from wastewater samples were then tested against the pathogen bacterial cultures in vitro. Biofilm disruption assay and genetic analysis of the strains were also performed. Bacteriophages with lytic activity could be identified from samples of two patients. One patient contained four strains showing strong efficacy against his own Staphylococcus epidermidis. Furthermore, this bacterium was susceptible to phages identified from another patient and strains from wastewater samples. Genomic analysis suggested lysogenic lifestyle of the phages. However, none of them have shown any microbiological signs of lysogeny. In conclusion, we have been able to prove in vitro lytic activity of bacteriophages originating from the same LVAD patient. We also found effective phages in biological samples of other patients and wastewater samples, suggesting that patients implanted in the same center may share bacteriophage flora.

Abstract: Central Africa exhibits the highest genetic diversity of HIV-1 globally, reflecting its role as the region where the virus first emerged. A product of this diversity is the increased prevalence of drug resistance mutations (DRMs), which has been documented in the region, particularly to NRTIs and NNRTIs, highlighting the importance of studying this diversity. This has led to a significant amount of literature being produced on the topic, although it is scattered throughout multiple niche sources, investigates different populations and reports variable outcomes. This review aims to compile this information, offering pooled regional and country-level proportions of subtypes, recombinant forms and individual DRMs, exploring their evolution from 2000 to 2025. To achieve these objectives, a meta-analysis will be performed for each subtype classification and individual DRM, with a subgroup analysis using the country of origin of the samples and a meta-regression analysis using the sample collection date. Methodological quality of the studies will be addressed using a proper tool for systematic reviews of prevalence, heterogeneity using the I² statistic, and publication bias using Egger’s regression test. Finally, a bibliometric analysis will provide an overview of the research landscape in HIV-1 molecular epidemiology in Central Africa and enhance the understanding of subtype distribution and diversity hotspots.

Abstract: Angola is one of the countries with the highest HIV-1 genetic diversity, yet the implications of this diversity for antiretroviral therapy remain insufficiently characterised. Following the introduction of dolutegravir (DTG) in Angola in 2021, evaluating transmitted drug resistance prior to its widespread implementation is essential to inform treatment strategies and establish a baseline for future surveillance. In this study, 243 blood samples were collected from treatment-naïve people living with HIV attending the General Hospital of Benguela, Angola. The integrase coding region of proviral DNA was amplified and sequenced using the Sanger method. Phylogenetic relationships were inferred using a maximum likelihood approach, recombinant forms were characterised by bootscanning analysis, and resistance-associated mutations to integrase strand transfer inhibitors were identified using Stanford HIVdb, ANRS-MIE, and IAS-USA algorithms. A total of 92 integrase sequences were successfully obtained, revealing 16 distinct genetic forms, with unique recombinant forms accounting for 50.0%, followed by subtype C (10.9%) and sub-subtype F1 (8.7%). Five accessory mutations (L74I, L74M, Q95K, T97A, and E157Q) and one major mutation (E92G) were detected, corresponding to an overall prevalence of 28.4%. These findings highlight the extensive HIV-1 genetic complexity in Angola and support the continued use of DTG-based regimens, while underscoring the importance of sustained surveillance of integrase inhibitor resistance.

Abstract: The Hepatitis E virus (HEV) is a zoonotic virus of global concern that circulates in both domestic and wild pig populations. Understanding its presence and dynamics in wildlife reservoirs is crucial for assessing spillover risks and designing One Health surveillance strategies. HEV is classified into eight distinct genotypes, two of which (genotypes 3 and 4) infect both humans and swine, representing a major public health concern in Europe. This study explored the occurrence, genetic diversity, and evolutionary relationships of HEV in wild boars (Sus scrofa scrofa) from mainland Portugal. Organ samples from a total of 120 wild boar were collected from seven different districts in Portugal. HEV RNA was detected in four animals (3.3%), all of which were collected from municipalities in the Évora district, near the land border with Spain. Of the four wild boars that tested positive for HEV in the diagnostic context, it was possible to genotype and characterize one through full sequencing. Phylogenetic analysis based on the complete genome, revealed that this strain clustered with predominantly human-derived HEV-3m sequences from Spain and France, highlighting its zoonotic potential. The inclusion of 14 sequences from domestic swine in a second phylogenetic analysis performed with a small fragment allowed to conclude that sub-genotypes 3e, 3f and 3m are circulating in this population with no spatial or temporal segregation. Phylogeographic analysis suggests that there have been several transmission events between Spain and France and estimated that this HEV strain is most likely to have been introduced from Spain. The fact that these four positive samples from wild boar in south-eastern Portugal all have a common spatial origin, together with the absence of detections in the other six districts tested and the presence of known HEV hotspots in south-western Spain, supports the hypothesis that this strain in Portugal is most likely from HEV circulation in Spanish wild boar, facilitated by cross-border movement of wild boar along the south-eastern Portuguese border. Although recombination events were identified in several HEV-3 strains, none were detected in the sequence obtained in this study or in other HEV-3m strains. This study provides the first molecular evidence of HEV-3m circulation in wild boars in Portugal, offering valuable insight into the HEV strain circulation in European wildlife populations. The zoonotic potential of HEV and the likelihood of interspecies transmission highlight the need for coordinated cross-border surveillance and integrated One Health strategies.

Abstract: Human endogenous retroviruses (HERVs) are potential driving forces of the pathophysiology of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), linking post-infectious immune dysfunction to chronic inflammation and immune and neurocognitive dysfunction that are hallmark features of ME/CFS. Accumulating evidence from related autoimmune diseases and cancers has shown that reactivated HERVs can contribute to disease pathogenesis by amplifying immune activation through viral protein-mediated innate sensing, Long Terminal Repeat (LTR)-driven transcription, and disrupting epigenetic silencing. HERV signatures are therefore promising biomarkers for diagnosis, patient stratification for drug-repurposing trials, and therapy monitoring. Accumulating evidence suggests a possible correlation between HERV expression and ME/CFS symptom severity, alterations of immune phenotypes, function and inflammatory gene networks. Importantly, locus-specific HERV profiling is a promising approach for distinguishing ME/CFS from overlapping or co-morbid conditions and healthy controls. Furthermore, HERV-targeted antibodies, immune modulators, epigenetic and antiviral interventions offer promise as concomitant therapeutic strategies for ME/CFS. Additional research incorporating viromics and other-omics validation, functional assays, and HERV-stratified clinical trials is now needed to realise this potential and to transform ME/CFS from a symptom-based syndrome into a mechanism-driven, treatable condition.

Abstract: Schmallenberg virus (SBV) has evolved from an emergent Orthobunyavirus identified in Europe in 2011 into an endemic pathogen with complex epidemiological dynamics. This review synthesizes advances in SBV research over the past 15 years, focusing on molecular pathogenesis, transmission ecology, and control strategies. We highlight the NSs protein as a key interferon antagonist, the mechanisms underlying fetal neurotropism, and the influence of climate change on Culicoides vector biology. Recent evidence of winter vector activity challenges traditional assumptions of transmission seasonality, with implications for disease management and trade regulations. Advances in diagnostics and vaccine development—including DIVA‑compatible and mRNA platforms—are critically evaluated, highlighting progress and persistent implementation gaps. Finally, we propose SBV as a model system for understanding arbovirus persistence and emergence in temperate regions within a One Health framework.

Abstract: High-throughput sequencing (HTS) was applied to investigate the virome of European beech (Fagus sylvatica) from asymptomatic leaves and leaves exhibiting chlorosis, line patterns and malformation. Total RNA extracted from six samples, including herbarium material collected in 1967 and 1968 and contemporary samples from France, Germany, and the Netherlands, was subjected to Illumina sequencing followed by de novo assembly, sequence similarity searches and phylogenetic analyses. In each sample, contigs belonging to a previously undescribed virus within the genus Carlavirus were obtained. The virus was tentatively named beech carlavirus. The detection of the virus over more than five decades and in three European countries indicates its long-term and a probable wider occurrence and circulation. Moreover, its prolonged unnoticed presence suggests that it does not induce noticeable and acute disease outbreaks. These findings underscore the value of integrating historical and recent field samples through collaborative data sharing to improve insight into virus diversity and ecology in forest trees.

Abstract: Madagascar experienced a severe measles epidemic between September 2018 and mid-2019, resulting in over 146,000 cases and 1,200 deaths, primarily among children under 15. This epidemic occurred in a context of low vaccination coverage. Prior to this epidemic, no genotyping data for the measles virus (MeV) or rubella virus (RuV) were available for Madagascar. This study aimed to molecularly characterize MeV and RuV strains circulating during the epidemic. A total of 310 biological samples (gingival swabs, urine, and stool) were collected from 288 suspected patients with a mean age of 11.4 years. Viral detection was performed by real-time RT-PCR, followed by conventional RT-PCR and sequencing for genotyping of the N and H genes of MeV and the E1 gene of RuV. The results revealed co-circulation of the two viruses, with detection rates of 39.9% (115/288) for MeV and 40.0% (70/175) for RuV. The mean age differed significantly between MeV-positive (12.0 years) and RuV-positive (7.2 years) patients, with 35.1% and 43.8% of cases occurring in children under five years of age, respectively. Phylogenetic analysis identified all MeV strains as belonging to genotype B3, showing high similarity to strains circulating globally in 2018-2019, suggesting recent importation. Meanwhile, the phylogenetic profile of RuV strains, all belonging to genotype 2B and displaying greater genetic diversity, was characteristic of endemic rubella in a partially vaccinated or unvaccinated population. This study provides the first genotyping data for Madagascar, essential for monitoring virus circulation and supporting elimination efforts in the African region.

Abstract: Bluetongue virus (BTV), the prototype orbivirus, infects livestock, causing high morbidity and mortality and impacting global trade. BTV is a non-enveloped, double-capsid virus, composed of seven structural proteins and a genome of ten double-stranded RNA segments. This manuscript highlights our recent findings on the molecular and structural mechanisms underlying BTV entry and assembly during replication. Viral entry is a stepwise, pH-dependent process. The virus-neutralisation, outermost protein VP2 attaches to sialic acids and senses the acidic pH of early endosomes, triggering its dissociation. Subsequently, the second outer capsid protein, VP5, undergoes major changes in late endosomes, forming a membrane-penetrating pore that releases the transcriptionally-active inner core into the host cytoplasm. Core assembly also proceeds stepwise and requires accurate packaging of ten positive-sense RNA segments. These segments form an RNA–RNA interaction network independent of viral proteins, beginning with the smaller segments and guiding complete genome assortment. The small capsid protein VP6, interacts with VP3 to facilitate RNA encapsidation. While infectious cores assemble in-vitro without non-structural proteins, NS2 is essential for the in-vivo formation of viral inclusion bodies via liquid–liquid phase separation, concentrating viral components and promoting genome assembly. These comprehensive characterisations of BTV provide future control strategies for related reoviruses.

Abstract: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide, with zoonotic genotypes detected in humans and animals. In Africa, limited data exist on environmental HEV circulation. Here, we report the first detection of Rocahepevirus ratti (RHEV) in urban wastewater from Conakry, Guinea. From December 2024 to April 2025, Rocahepevirus ratti (RHEV) has been detected in 35 out of 180 urban untreated wastewater samples in Conakry, Guinea. Phylogenetic analysis of partial HEV ORF1 genome segments reveals clustering with African rodents RHEV strains, highlighting environmental contamination and potential zoonotic risk for human population in proximity. This finding underscores the need for integrated One Health surveillance to monitor HEV transmission at the human-animal-environment interface in West Africa particularly in Guinea.

Abstract: Enterovirus alphacoxsackie (EV-A) is a highly diverse viral species containing at least 25 serotypes of viruses which show distinct infectivity and pathogenicity. Increasing studies show that EV-A protease 2A plays critical roles in virus-host interactions. Although 2A is usually considered as a non-structural protein highly conserved among different EV-A serotypes, its orthologs of different EV-A serotypes harbor abundant single amino acid polymorphisms (SAPs), probably contributing to the variance of infectivity and patho-genicity of EV-As. However, the SAP profile of EV-A 2A and its functional impacts have been poorly understood, mainly due to the unequal contribution to protein function of dif-ferent SAP sites. Herein, we developed Single Amino Acid Polymorphism Statistics (SAAPS), an information-entropy-based algorithmic pipeline, to identify key SAP sites (kSAPs) related to functional variance of EV-A 2A. As the result, we identified 56 kSAPs from 2A of 25 EV-A serotypes. Based on the kSAPs, the 2As can be clustered into three major groups with a few outliers, which was distinct from the clustering generated by phylogenetic analysis using the whole amino acid sequences. Functional verification with transcriptomic profiles of HEK-293T cells expressing different 2A variants revealed better phenotypic matching of kSAP-based clustering than that of phylogenetic clustering. No-tably, EV-A89, an outlier identified by kSAP clustering but not phylogenetic clustering, showed unique expressing and self-cleavage patterns which were not observed in other 2As. These findings demonstrated the good performance of SAAPS and functional SAP profile of EVA 2As, contributing to the understanding of the variance of EV-A infectivity and pathogenicity.

Abstract: HIV-1 genetic diversity may influence the selection of antiretroviral drug resistance mutations (DRMs); however, subtype-specific resistance patterns remain incompletely characterized in East Africa, where subtype A1 predominates. We examined the distribution of genotypic DRMs across HIV-1 subtypes among patients with advanced HIV disease failing NNRTI-based first-line therapy in western Kenya. In this cross-sectional molecular sub-analysis, 65 hospitalized individuals (≥15 years) with virological failure (HIV-1 RNA ≥1000 copies/mL) had a 1,084-bp pol gene fragment sequenced. Subtypes were assigned using REGA. DRMs were identified using the Stanford HIV Drug Resistance Database. Associations between subtype and specific mutations were evaluated using Fisher’s exact test. Subtype A1 dominated (70.8%), followed by D (13.8%), recombinants (9.2%), and A2 (6.2%). We detected dual-class resistance in 73.8% of participants. The most frequent mutations were M184V (64.6%) and K103N/S (60.0%). Subtype A1 sequences were less frequently observed to have K101E/H (8.7%, p=0.011) and Y181C/I/V (17.4%, p=0.027) than non-A1 subtypes. No significant associations were observed between subtype and NRTI mutations. These findings suggest possible subtype-associated differences in NNRTI resistance patterns that warrant validation in larger studies, underscoring the importance of continued molecular surveillance to guide resistance monitoring and optimize long-term treatment strategies in the era of integrase inhibitor–based therapy.

Abstract: Soybean (Glycine max) is relatively recalcitrant to genetic manipulations, hence is often interrogated with transient means such as virus-induced gene silencing (VIGS). We earlier modified cowpea severe mosaic virus (CPSMV) to develop a soybean-friendly VIGS system referred to as QUIN-FZ. Here we report additional calibrations of this system. We enhanced the intra-bacterial stability of plasmid QUIN, which contained a CPSMV RNA1 cDNA embedded with four introns, by adding a fifth intron, resulting in PENTIN. We separately upgraded the plasmid FZ, which contained a modified CPSMV RNA2 cDNA with a cloning site in the middle of the viral polyprotein, by creating another cloning site within the 3’ untranslated region, leading to ZY. We next used the new PENTIN-ZY system to investigate a putative soybean protein kinase designated QL18. Virus-mediated overexpression of two allelic, 147-amino-acid (aa) protein fragments, derived from two different QL18 orthologs, elicited drastically different responses in soybeans. While the fragment derived from soybean accession OX20-8 prevented the cognate virus from infecting top young leaves in at least 50% of inoculated seedlings, its allelic counterpart derived from soybean accession PI427105B elicited apical necrosis in 100% of soybean seedlings. By examining progeny viruses as well as viruses encoding chimeras of the two fragments, we identified more than a dozen mutations that abrogated these unique phenotypes. Our findings establish the PENTIN-ZY system as a versatile tool for overexpressing small proteins and protein fragments, accelerating their functional characterization.

Abstract: Extracellular vesicles (EVs) can disseminate replication-competent viral genomes complexed with selected host proteins, enabling stealth cell-to-cell transfer within lipid membrane-enclosed bubbles. In addition to complementing free-virion spread, EV-associated genomes can be protected from neutralizing antibodies and persist under conditions in which classical virion production decreases. Here, we propose a route-resolved framework in which interconnected cellular secretory pathways, including endoplasmic reticulum (ER) remodeling, multivesicular body (MVB) biogenesis, secretory autophagy, and plasma-membrane budding, jointly generate EV heterogeneity and create discrete opportunities for the capture, protection, and export of infectious cargo. We highlight reticulon-3 (RTN3), an ER-shaping protein, as an upstream regulator that can couple infection-induced ER microdomains to endosomal docking and autophagy-linked trafficking decisions that bias intermediates toward secretion rather than degradation. Supporting this view, transmission electron microscopy of dengue virus-infected cells reveals extensive vesicular remodeling, including irregular MVBs adjacent to the plasma membrane and autophagosome-like double-membrane structures, consistent with altered vesicular routing following RTN3 perturbation. Collectively, these route-resolved, spatially organized spatio-organelle changes support a pathomechanistic model in which RTN3-mediated ER remodeling reshapes ER-endosome-autophagy trafficking interfaces, creating regulated decision points that can be leveraged to stratify infectious EV subsets (with infectivity-linked single-vesicle and quantitative proteomics approaches) and to inform host-directed strategies that curb non-lytic viral dissemination.

Abstract: TBEV is a major cause of viral central nervous system infections in Europe, with heterogeneous geographical distribution and substantial underdiagnosis in low-incidence regions. This study aimed to evaluate the validity of regional TBE risk classification in Poland by combining surveillance-based incidence data with serological markers of TBEV exposure. Plasma samples from 5,541 blood donors residing in nine regions were tested by anti-TBEV IgG ELISA, followed by confirmatory VNT, IFA and anti-NS1 IgG ELISA to differentiate infection-induced from vaccine-induced antibodies. Regions were classified based on average TBE incidence from 2015–2019. Overall, anti-TBEV IgG screening reactivity was detected in 4.9% of donors, with significant regional variation (p < 0.001). The highest seroprevalence was observed in highly affected regions; however, unexpectedly elevated seroprevalence was also detected in regions classified as low affected. Markers consistent with TBEV infection (anti-NS1 IgG) were identified in only 2.6% of donors, whereas vaccine-induced immunity accounted for the majority of seropositive results. Male sex was independently associated with higher odds of seropositivity. Our findings suggest that passive surveillance data alone may insufficiently capture population-level exposure to TBEV, particularly in regions considered non-endemic. Integrating sero-epidemiological data with surveillance systems may improve risk assessment and inform targeted prevention strategies.

Abstract: The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease via the double methylation of the 5' end of eukaryotic DNA or RNA-based viral genomes, the 7-MeGpppA2’-O-Me cap, and its double methylation capping process is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16) and by N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered that polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), and consequently, detection of Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs) alike. NSP1 also silences important interferon-encoding genes (INGs) and interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Another important viral NSP is NSP14, as it plays two functional roles that are independent of each other; to produce new viral genetic material for the purpose of maintaining the validity of the viral genome as well, and not just transfer a methyl group to the 5’ end of the viral genome. Other viral NSPs share a role with NSP1, 10, 14 and 16 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. With regards to efforts to delay the onset of malignant diseases, approaches of chrono-biological oncotherapies that include a combination of Type I and Type III Interferon-based “immune re-awakening” and low-dose SSRI or SNRI approaches, could display meaningful extents of efficacy, at least in effective delays in the onset of malignant diseases. Such overall approaches could also be considerably effective in efforts to delay and/or even prevent a number of acquired immunodeficiencies (i.e. HIV-1-induced AIDS) and diverse forms of malignant cancer, potentially helping to notably decrease the overall burden of disease worldwide in the long run. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases. Microbial agents could undergo loss-of-function research upon genes responsible for inducing clinical illness whilst keeping genes responsible for microbial reproduction and transmission at least generally as functional, CRISPR-Cas9 genome editing to have genes encoding proteins suppressive of the host interferon system eliminated prior to human genes encoding Pattern Recognition Receptor activator or agonist proteins, such as outer membrane proteins of Neisseria meningitidis, as well as Type I, Type III and possibly even Type IV Interferons and various ISGs inserted into the microbial genome. Importantly, the present study is theoretical and conceptual in nature and does not advocate for any practical steps or deployment into any real-world context. Such an approach is imagined as a potential prophylactic and early therapeutic method based upon the model of editing genes of harmless bacteria to transform such them into “producers” and “distributors” of human insulin, and could turn several microbial agents into clinically harmless, transmissible “factories” for various key elements of the host interferon system, potentially placing such microbes into a reverse evolutionary path that would be deemed as “natural de-selection”, visibly reducing the average burden of disease and metabolic stresses, which in turn could gradually increase average human and animal lifespans worldwide.

Abstract: Glucose and ascorbate transport and their opposite effects on the physiological processes, explain the pathophysiology of the Ebola virus. The virus impairs intracellularly the interferon (IFN) signalling. The present article will focus on the viral factors (VP24, VP35, VP40 proteins, nucleoprotein NP) that operate in the inner of the cell, subsequently to the viral entry. The haemorrhagic fever syndrome could be understood as a state of oxidative stress, driven by hyperglycaemia and the activation of NF-kB pathway and inflammatory cytokines. High glucose levels in plasma contributes to oxidative stress. It has also an inhibitory effect on Interferon (IFN) signalling. Conversely, ascorbate can counteract the IFN blocking exerted by the virus and interfere virus budding. A treatment strategy would focus on the administration of ascorbate and glutathione, glucose or insulin at convenience, in order to maintain constant and normal levels of glucose in plasma, to combat the oxidative and inflammatory stress.

Abstract: Translational virology, characterized as “from bench to bedside”, covers all issues from basic research through clinical evaluation and final registration and drug/vaccine approval. It covers the identification of the cause of disease, screening of potential prophylactic or therapeutic agents, evaluation in animal models, confirmation of activity in human clinical trials, registration and approval. The recent COVID-19 pandemic represents a perfect example of translational virology, which demonstrated an unprecedented cooperation from the identification of the SARS-CoV-2 to the rapid development of potential repurposed and novel drugs and vaccines for both prophylactic and therapeutic applications. After confirmation of therapeutic and prophylactic efficacy in animal models, clinical phase I-III evaluation was carried out in an overlapping strategy, reducing the development time significantly. To maximize the chances of success, vaccines based on whole viruses, protein and peptide subunits, viral vectors and nucleic acids were developed in parallel. Based on good safety profiles and robust immune responses, COVID-19 vaccine candidates were granted emergency use authorization worldwide allowing the start of mass vaccinations. More than 13.6 billion COVID-19 vaccine doses have been administered, and although severe adverse events have been registered millions of lives have been saved. Due to emerging SARS-CoV-2 variants vaccine re-engineering has been required as part of translational virology. Vaccine production, storage, transport and distribution have also been given attention.

Abstract: This review explores a hypothetical and previously underexplored ecological pathway that may contribute to virus dispersal, including human pathogens, through passive transport involving free-living nematodes and migratory animals. Available data on nematode-associated viruses, nematode survival in diverse environments, and mechanisms of passive dispersal are synthesized to propose a conceptual framework for long-distance pathogen movement. Particular attention is given to the ecological interactions among nematodes, animals, and viruses, and to the potential role of these interactions in shaping pathogen distribution patterns under environmental and anthropogenic pressures. The article discusses a theoretical model of possible virus transfer across ecological niches and highlights key gaps requiring experimental validation. This study highlights a previously underestimated route of potential virus transmission, including human pathogens, through possible long-distance dispersal (500 km or more) by free-living nematodes and migratory birds. Data on the spread of viruses of nematodes of the genus Caenorhabditis spp., the survival of nematodes in various conditions, and their spread by various groups of animal carriers, including their ability to pass through the gastrointestinal tract of birds in a viable state, are analyzed. The role of a number of migratory bird species as biological carriers not only of free-living nematodes themselves over considerable distances, but also of viruses hypothetically associated with nematodes on/inside their bodies, is considered as a potential mechanism. This work raises questions about previously underestimated biological risk factors associated with this potential route of passive pathogen dispersal to new territories and ecological niches, especially in conditions of environmental stress, intensive animal husbandry, and global movement of wild animals. The article discusses a hypothetical scenario in which SARS-CoV-2 and other viruses could be passively dispersed through ecological interactions involving nematodes and migratory birds. Understanding the ecological dynamics of the interaction between birds, nematodes, and virusesmay contribute to ecological risk assessment and understanding of emerging pathogen dynamics. This manuscript presents a conceptual ecological hypothesis and should not be interpreted as evidence of confirmed transmission pathways.