Search Results (94)

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

The agents of prion diseases have the capacity to efficiently infect susceptible hosts by peripheral routes and to project to clinical target areas of the central nervous system (CNS) via peripheral nerves. Understanding the process of prion spread from the site of infection to the CNS may allow us to identify novel therapeutic strategies. To investigate the mechanism involved in the intranerval transit of 263K scrapie prions in golden Syrian hamsters (GSHs), we transected the sciatic nerve at increasing times post-footpad injection and recorded the incubation periods as estimates of the efficiency of infection. We calculated that intranerval transit of this strain of scrapie is at least 10 times faster than previously reported and may reach 50 mm/day, similar to other neurotropic viruses. By in vivo exposure/injection of sciatic nerves to 263K infectivity, we have also shown that prion entry likely occurs via nerve terminals rather than by direct contact with the sciatic nerve. Application of this experimental approach in other forms of prion diseases could allow verification of the timing of neuroinvasion, a relevant parameter for the definition of therapeutic interventions. Full article

Background/Objectives: The aetiology of Bell’s palsy remains unclear and is typically diagnosed by exclusion. This study investigated the potential role of neurotropic viruses and explored the relationship between facial nerve impairment and vestibular dysfunction to improve the understanding of the condition. Methods: Antibodies against herpes simplex virus (HSV) and varicella-zoster virus (VZV) were assessed using ELISA. Vestibular function was evaluated through computerised videonystagmography, rotatory chair, and clinical vestibulospinal assessments. Facial nerve lesion localisation was determined by stapedial reflex testing. Fisher’s exact test was used for statistical analysis. Results: Of 51 patients with Bell’s palsy, 62.7% exhibited vestibular dysfunction, and 70.6% were IgG-positive for at least one neurotropic virus. Vestibular impairment was significantly more common in seropositive patients. Statistically significant associations were observed between vestibular dysfunction and viral IgG seropositivity (p < 0.0001), the severity of vestibular dysfunction and facial paresis (p = 0.0126), and the side of vestibular impairment and the side of facial palsy (p < 0.0001), with 90.6% of cases showing ipsilateral involvement. Conclusions: These findings support the hypothesis that neurotropic viruses may act as a common pathological factor in both Bell’s palsy and associated vestibular dysfunction. Full article

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article

Anseriformes (waterfowl) and Charadriiformes (shorebirds) are well-recognized natural reservoirs of low pathogenic (LP) influenza A viruses (IAVs). Historically, LP IAVs circulate among healthy individuals during seasonal, and often transcontinental, migrations. However, following the introduction of clade 2.3.4.4b highly pathogenic (HP) A/Goose/Guangdong/1/1996 lineage H5 IAV to North America in 2021, countless wild birds succumbed to fatal infections across the Western Hemisphere. Due to their small size and cryptic plumage patterns, opportunities for carcass recovery and postmortem evaluation in sanderlings (Calidris alba) and other shorebirds are rare. A multispecies mortality event in coastal Virginia, USA, in March–April 2024 included sanderlings among other wild bird species. Nine sanderlings underwent postmortem evaluation and clade 2.3.4.4b H5 IAV RNA was detected in pooled oropharyngeal-cloacal swabs from 11/11 individuals by real-time reverse transcription polymerase chain reaction. Histopathology was similar to that in waterfowl and included necrosis in the pancreas and brain and less commonly in the gonad, adrenal gland, spleen, liver, and intestine. Immunohistochemistry revealed IAV antigen labeling in necrotic neurons of the brain (neurotropism) and epithelial cells of the pancreas, gonad, and adrenal gland (epitheliotropism). Describing HP IAV-attributed pathology in shorebirds is key to understanding ecoepidemiology and population health threats in order to further document and compare pathogenesis among avian species. Full article

Lyssaviruses are RNA viruses in the Family Rhabdoviridae, Genus Lyssavirus. They represent the causative agents of acute, progressive encephalitis, known historically as rabies. Regardless of specific etiology, their collective viral morphology, biochemistry, pathobiology, associated clinical signs, diagnosis, epizootiology, and management are essentially the same. Despite centuries of clinical recognition, these quintessential neurotropic agents remain significant pathogens today, with substantive consequences to agriculture, public health, and conservation biology. Notably, the singular morbidity caused by lyssaviruses is incurable and constitutes the highest case fatality of any viral disease. All warm-blooded vertebrates are believed to be susceptible. The dog is the only domestic animal that serves as a reservoir, vector, and victim. In contrast, felids are effective vectors, but not reservoirs. All other rabid domestic species, such as livestock, constitute spillover infections, as a bellwether to local lyssavirus activity. Frequently, professional confusion abounds among the veterinary community, because although the viral species Lyssavirus rabies is inarguably the best-known representative in the Genus, at least 20 other recognized or putative members of this monophyletic group are known. Frequently, this is simply overlooked. Moreover, often the ‘taxonomic etiology’ (i.e., ‘Lyssavirus x’) is mistakenly referenced in a biopolitcal context, instead of the obvious clinical illness (i.e., ‘rabies’). Global consternation persists, if localities believe they are ‘disease-free’, when documented lyssaviruses circulate or laboratory-based surveillance is inadequate to support such claims. Understandably, professional chagrin develops when individuals mistake the epidemiological terminology of control, prevention, elimination, etc. Management is not simple, given that the only licensed veterinary and human vaccines are against rabies virus, sensu lato. There are no adequate antiviral drugs for any lyssaviruses or cross-reactive biologics developed against more distantly related viral members. While representative taxa among the mammalian Orders Chiroptera, Carnivora, and Primates exemplify the major global reservoirs, which mammalian species are responsible for the perpetuation of other lyssaviruses remains a seemingly academic curiosity. This zoonosis is neglected. Clearly, with such underlying characteristics as a fundamental ‘disease of nature’, rabies, unlike smallpox and rinderpest, is not a candidate for eradication. With the worldwide zeal to drive human fatalities from canine rabies viruses to zero by the rapidly approaching year 2030, enhanced surveillance and greater introspection of the poorly appreciated burden posed by rabies virus and diverse other lyssaviruses may manifest as an epidemiological luxury to the overall global program of the future. Full article

Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) is the most common form of dementia and typically manifests in individuals aged over 65 years; however, it also occurs in a small number of individuals aged less than 65 years. A combination of environmental, genetic, and lifestyle factors is believed to contribute to the development of AD. There have been several reports describing potential associations of infections or reactivations of human alphaherpesviruses with AD. A particular characteristic of human alphaherpesviruses (herpes simplex viruses 1 and 2, varicella zoster virus) is that they are neurotropic and that lifelong infection (latency) is established mainly in the dorsal root and trigeminal ganglia. There have also been reports that suppression of alphaherpesvirus infections through either vaccination or the application of antiviral treatments may be protective against the development of AD. Zoster vaccines and acyclovir may prove to be effective interventions for preventing or limiting the progression of AD. This is particularly relevant as there are currently no available cheap and effective treatments for AD. In this review, the basic virology of human alphaherpesviruses is described followed by their epidemiology and associations with AD. Finally, the prevention and treatment of human alphaherpesviruses are considered in the context of potential applications for the prevention of AD. Full article

Aging is the result of various compounding stresses that gradually overcome the homeostatic regulation of the cell, resulting in irreversible damage. This manifests as many acute and chronic conditions, the most common of which are neurodegeneration and dementia. Epidemiological studies have shown significant, strong correlations between viral infection and neurodegenerative diseases. This review overlays the characteristics of viral pathogenesis with the hallmarks of aging to discuss how active and latent viruses contribute to aging. Through our contextualization of myriad basic science papers, we offer explanations for premature aging via viral induction of common stress response pathways. Viruses induce many stresses: dysregulated homeostasis by exogenous viral proteins and overwhelmed protein quality control mechanisms, DNA damage through direct integration and epigenetic manipulation, immune-mediated oxidative stress and immune exhaustion, and general energy theft that is amplified in an aging system. Overall, this highlights the long-term importance of vaccines and antivirals in addition to their acute benefits. Full article

Orthobunyaviruses are a diverse group of segmented RNA viruses with significant but underexplored public and veterinary health implications. This study provides a genomic, phylogenetic, and ecological analysis of neglected Orthobunyaviruses using next-generation sequencing and computational predictions. We identified unique phylogenetic relationships, with Tanga virus forming a distinct lineage linked to zoonotic, human-associated, or non-vertebrate viruses across segments. GC content analysis revealed segment-specific patterns: higher GC content in the S segment suggests genomic stability and immune evasion, while lower GC content in the L segment reflects host-vector adaptation. Phylogenetic ties to well-characterized pathogenic viruses, such as Ilesha virus with Cache Valley virus and Bwamba virus with California encephalitis virus, indicate potential neurotropism. Ingwavuma virus clustered with Oropouche virus, suggesting risks of systemic febrile illnesses. Within the Simbu serogroup, Sango and Sabo viruses show teratogenic risks to livestock. Vector and host predictions implicate rodents, artiodactyls, and primates in Orthobunyavirus transmission, emphasizing complex ecological dynamics and zoonotic potential. These findings advance the understanding of Orthobunyavirus diversity, linking genomic features to pathogenicity and ecological adaptation, while providing a foundation for future surveillance and intervention strategies targeting these neglected viruses. Full article

Flaviviruses, a group of single-stranded RNA viruses spread by mosquitoes or ticks, include several significant neurotropic viruses, such as West Nile virus (WNV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Zika virus (ZIKV). These viruses can cause a range of neurological diseases during acute infection, from mild, flu-like symptoms to severe and fatal encephalitis. A total of 20–50% of patients who recovered from acute flavivirus infections experienced long-term cognitive issues. Here, we discuss these major neurotropic flaviviruses-induced clinical diseases in humans and the recent findings in animal models and provide insights into the underlying disease mechanisms. Full article

Host–pathogen interactions and the design of vaccines for aquaculture fish viruses are challenging and call for innovative approaches. This study explores the potential of adenoviral (Ad) vectors Ad5 and chimeric Ad5/40 as gene delivery tools for fish brain cells susceptible to neurotropic viruses. For this purpose, European sea bass (Dicentrarchus labrax) DLB-1 and gilthead seabream (Sparus aurata) SaB-1 brain cell lines were infected with Ad5 or Ad5/40 vectors expressing GFP, and we evaluated their capacity for infection by fluorescence microscopy and flow cytometry, as well as their antiviral innate immune response by the transcription of gene markers (irf3 and mx). We found that both vectors are able to infect DLB-1 and SaB-1 brain cell lines to similar levels, as demonstrated by fluorescence microscopy and flow cytometry, though the infection efficiency was low. In addition, infection with Ad vectors regulated the transcription of genes related to the interferon-mediated antiviral immune response. Our results indicate that the Ad5/40 vector achieves better infection and consistent cellular distribution. These findings suggest that these vectors may offer targeted gene delivery and local immune responses. Full article

Inflammation of the brain is called encephalitis and may result in acute and chronic brain damage. Encephalitis can be caused by various pathogens, especially neurotropic viruses, or can occur in the context of autoimmune diseases. Encephalitis is often difficult to diagnose and to monitor precisely during the course of the disease. Thanks to highly specific detection technology, components of the neuron skeleton, such as neurofilaments, can now be reliably quantified in the peripheral blood besides cerebrospinal fluid (CSF). Among them, neurofilament light chain (NfL) has demonstrated wide utility due to high preanalytical stability, robust diagnostic technology, and excellent reproducibility. We provide an overview of how NfL has advanced diagnostics in encephalitis and outline future avenues in research needs and possible clinical applicability of NfL in adults and children. Full article

Alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV), infect a diverse array of hosts, spanning both humans and animals. Alphaherpesviruses have developed a well-adapted relationship with their hosts through long-term evolution. Some alphaherpesviruses exhibit a typical neurotropic characteristic, which has garnered widespread attention and in-depth research. Virus latency involves the retention of viral genomes without producing infectious viruses. However, under stress, this can be reversed, resulting in lytic infection. Such reactivation events can lead to recurrent infections, manifesting as diseases like herpes labialis, genital herpes, and herpes zoster. Reactivation is a complex process influenced by both viral and host factors, and identifying how latency and reactivation work is vital to developing new antiviral therapies. Recent research highlights a complex interaction among the virus, neurons, and the immune system in regulating alphaherpesvirus latency and reactivation. Neurotropic alphaherpesviruses can breach host barriers to infect neurons, proliferate extensively within their cell bodies, and establish latent infections or spread further. Whether infecting neurons or spreading further, the virus undergoes transmission along axons or dendrites, making this process an indispensable part of the viral life cycle and a critical factor influencing the virus’s invasion of the nervous system. Research on the transmission process of neurotropic alphaherpesviruses within neurons can not only deepen our understanding of the virus but can also facilitate the targeted development of corresponding vaccines. This review concentrates on the relationship between the transmission, latency, and activation of alphaherpesviruses within neurons, summarizes recent advancements in the field, and discusses how these findings can inform the design of live virus vaccines for alphaherpesviruses. Full article

Background: Chorea is a neurological disorder characterized by random, fluid movements that may affect the limbs, trunk, neck, or face. In children, Sydenham’s chorea (SC) is the most common cause of acute chorea, mainly following group A beta-hemolytic streptococcal (GABHS) infection. Other autoimmune and metabolic disorders may also cause chorea. Case presentation: We report the case of a 6-year-old girl who developed chorea following cardiac surgery for mitral insufficiency. One week after discharge, the patient presented with right-sided hyposthenia, slower speech, mild dysarthria, and sialorrhea. Brain MRI and intracranial MRI angiography revealed a small vascular lesion consistent with a microembolic event. Extensive diagnostic investigations, including serum panels for autoimmune encephalitis, neurotropic viruses, and metabolic disorders, were negative. Conclusions: Considering the patient’s history, clinical course, and the exclusion of other potential causes, a diagnosis of post-pump chorea was made. This case underlines the importance of a thorough differential diagnosis in pediatric chorea and highlights post-pump chorea as a significant postoperative complication in pediatric cardiac surgery. The patient’s motor symptoms improved with symptomatic treatment, and follow-up showed good recovery without neurological sequelae. Full article

Pseudorabies virus (PRV) is one of the herpes viruses that can infect a wide range of animals including pigs, cattle, sheep, mice, and wild animals. PRV is a neurotropic alphaherpesvirus capable of infecting a variety of mammals. There is a rising interest in the targeted application of probiotic bacteria to prevent viral diseases, including PRV. In this study, the surface expression of enhanced green fluorescent protein (EGFP) on recombinant Lactiplantibacillus plantarum NC8 (rNC8) through the LP3065 LPxTG motif of Lactobacillus plantarum WCFS1 was generated. The surface expression was observed through confocal microscopy. Dendritic cell targeting peptides (DCpep) were also fused with LPxTG that help to bind with mouse DCs. The PRV-gD was cloned in LP3065 LPxTG, resulting in the generation of rNC8-LP3065-gD. Inactivated rNC8-LP3065-gD was administered intravenously in mice on days 1 and 7 at a dose of 200 µL (10⁹ CFU/mouse) for monitoring immunogenicity. Subsequently, a challenge dose of PRV TJ (10⁴ TCID₅₀) was administered intramuscularly at 14 days post-immunization. The survival rate of the immunized mice reached 80% (4/5) with no significant signs of illness. A significant rise in anti-gD antibodies was detected in the immunized mice by ELISA. Quantitative PCR (qPCR) results showed decreased viral loading in different body tissues. Flow cytometry of lymphocytes derived from mice spleen indicated an increase in CD3⁺CD4⁺ T cells, but CD3⁺CD8⁺ T cells were not detected. Moreover, it offers a model to delineate immune correlates with rNC8-induced immunity against swine viral diseases. Full article