Search Results (474)

Emerging evidence suggests that viral infections may contribute to the onset and progression of Alzheimer’s disease (AD) and other forms of dementia. Understanding the mechanism of viral involvement in the pathogenesis of AD and related dementia (ADRD) could contribute to reducing the burden caused by these conditions, which affect a large portion of the aging population. Some studies indicate the link between AD and viral infections, notably coronaviruses and herpesviruses. In AD, excessive production of reactive oxygen species (ROS) results in the modifications of lipids, proteins, and nucleic acids, contributing to synaptic dysfunction and cognitive impairments. Experimental evidence suggests that viral infections linked to ADRD induce the cellular production of ROS, possibly contributing to the pathogenesis of these conditions. Despite significant advances in defining the roles of ROS in neurological disorders and viral infections, the specific roles of ROS in virus-associated ADRD have not been thoroughly investigated. The main objective of this review article is to comprehensively provide information on the experimental evidence for the production of ROS by viruses to help the readers investigate the role of ROS in the relationship between viral infections with ADRD. Full article

Background/Objectives: Polymerase chain reaction (PCR) testing of ocular fluids is an essential diagnostic method for identifying infectious causes of uveitis. However, multiplex PCR kits specifically developed for ophthalmic use are not commercially available in many regions, including Korea. Given the biochemical similarity between cerebrospinal fluid (CSF) and aqueous humor, this study evaluated the diagnostic utility of a commercially available CSF multiplex PCR panel for detecting herpesviruses in patients with suspected viral uveitis. Methods: We retrospectively reviewed the medical records of patients whose aqueous humor samples were analyzed using a multiplex PCR assay originally designed for CSF testing (Seeplex Meningitis-V1 ACE Detection kit, Seegene, Seoul, Republic of Korea). The samples were obtained between May 2019 and June 2023 at two tertiary referral hospitals. The assay targeted herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human herpesvirus 6 (HHV-6). Patients were classified into three groups: (I) anterior uveitis with suspected herpesviral infection, (II) acute retinal necrosis (ARN), and (III) CMV retinitis. Baseline characteristics, PCR positivity rates, and virus prevalence were compared among the groups. Results: Among 149 eyes tested, 86 were included in the final analysis. The overall positivity rate was 38.4%. PCR positivity was 19.7% (12/61) in Group I, 93.8% (15/16) in Group II, and 66.7% (6/9) in Group III. CMV was the most common pathogen in Groups I (66.7%) and III (100%), while VZV was predominant in Group II (80%). No HHV-6 infection was detected. Conclusions: The positivity rate in anterior uveitis (Group I) was lower than previously reported, likely due to the limited sample volume relative to the assay’s requirement. Nevertheless, the assay demonstrated diagnostic reliability comparable to previous reports for ARN and CMV retinitis. Therefore, the CSF-based multiplex PCR panel serves as a feasible and cost-effective diagnostic option for sight-threatening posterior segment infections, facilitating prompt diagnosis and treatment, although further optimization is warranted for anterior uveitis. Full article

The epidemiology of central nervous system (CNS) infections caused by herpesviruses varies with host factors and geographic distribution. Timely diagnosis and therapeutic intervention are life-saving. This study investigated the epidemiology of herpesvirus CNS infections in Western Greece, compared clinical and laboratory findings with international data and evaluated an internal laboratory algorithm for cerebrospinal fluid (CSF) molecular testing criteria. During the study period, 940 of 4300 CSF samples met eligibility criteria for RT-PCR detection of herpes simplex virus (HSV-1, HSV-2) and varicella zoster virus (VZV). Of these, 53 (5.63%) were positive: 37 VZV, 9 HSV-1, and 7 HSV-2. HSV-2 cases occurred in younger patients (median age 41) and had the highest CSF white blood cells (WBC) counts (231/mm³), followed by VZV (125/mm³) and HSV-1 (26/mm³). CSF protein was higher in HSV-2 infections. Magnetic resonance imaging (MRI) was the most sensitive imaging modality for detecting CNS inflammation. These results indicate VZV as the predominant herpesvirus in this region, underscoring the need for high clinical suspicion in older patients and timely molecular diagnosis. Full article

Porcine cytomegalovirus, more accurately classified as porcine roseolovirus (PCMV/PRV), was shown to be pathogenic in the context of xenotransplantation. Transmission of PCMV/PRV to non-human primates receiving hearts or kidneys from virus-positive pigs significantly reduced the survival time of the recipients. PCMV/PRV was also transmitted to the first human recipient of a pig heart transplant and contributed to the patient’s death. Although PCMV/PRV is highly prevalent in all pig breeds and wild boars, including slaughterhouse pigs, no infections or diseases have been reported in healthy, ill, or immunocompromised humans, suggesting that this virus is not zoonotic and should therefore be classified as xenozoonotic. This indicates that this virus is not zoonotic and must be classified as xenozoonotic. Moreover, it remains unclear whether PCMV/PRV is capable of infecting human cells in vitro. To address this question, human 293T cells resistant to hygromycin were co-cultured with porcine fallopian tube (PFT) cells producing PCMV/PRV. After hygromycin selection, the remaining human cells showed no evidence of infection. Because herpesviruses are generally considered to be species-specific—a notion that has been shown to be not entirely correct—it was also investigated whether PCMV/PRV can infect mouse cells using the same approach. Similarly, no infection was observed. Since the target cells employed in both assays had a reduced capacity to resist viral infection, the findings strongly suggest that PCMV/PRV is unable to infect human or mouse cells, which are equipped with functional antiviral mechanisms. This is supported by findings from the patient who received the first pig heart transplantation. Full article

The livestock industry experiences significant economic losses as a result of viral infections. Building on recent advances in biotechnological research, recombinant viral vector vaccines have emerged as promising platforms for next-generation vaccines. These vaccines can overcome many limitations of conventional vaccines, as they provide stronger protective immune profiles, stability, and improved safety profiles for various diseases. Bovine herpesviruses serve as viral vector platforms utilized due to their large genome capacity, potential for multigenic antigen delivery, and significant immune stimulation. In this review, we explored the structural characteristics and genomic organization of bovine alphaherpesviruses (BoHV-1, BoHV-4, and BoHV-5), covered BoHV-5 biology and attenuation strategies as part of the comparative platform analysis, and summarised the latest advancements in molecular tools used for viral genome editing. We further highlight the development of vaccines against bovine and zoonotic pathogens, discuss applications of BoHV-based vectors, and deliberate on future directions to improve vaccine efficacy. It also discussed the current state of research in the field, considered prospects, and outlined strategies for impending research. BoHV vectors are promising candidates as next-generation vaccine platforms in veterinary medicine and will play an important role in integrated disease control in livestock. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness with unknown etiology. An estimated 17–24 million people representing approximately 1% of the population are afflicted worldwide. In over half of cases, ME/CFS onset is associated with acute “flu-like” symptoms, suggesting a role for viruses. However, no single virus has been identified as the only etiological agent. This may reflect the approach employed or more strongly the central dogma associated with herpesviruses replication, which states that a herpesvirus exists in two states, either lytic or latent. The purpose of this review is to address the role that abortive lytic replication may have in the pathogenesis of ME/CFS and other post-acute viral infections and also to raise awareness that these syndromes might be poly-herpesviruses mediated diseases. Full article

Background: Cutaneous viral infections, defined as viral pathogens that either primarily affect the skin (e.g., herpesviruses, enteroviruses) or frequently produce dermatologic manifestations despite systemic tropism (e.g., HIV, SARS-CoV-2), can trigger systemic inflammatory and neurotropic responses that extend their impact to the nervous system. A growing body of evidence suggests that viruses with dermatologic manifestations may play a significant role in the pathogenesis of neurologic disorders. Summary: Although individual viruses have been studied in isolation, the skin–brain axis in viral infections remains incompletely characterized. This review synthesizes existing knowledge and highlights gaps in understanding the mechanisms linking cutaneous viral infections to neurologic disease. We explore the principal mechanisms linking viral skin infections to central and peripheral nervous system damage, including direct neuroinvasion, immune-mediated injury, and vascular or endothelial dysfunction. Particular attention is given to herpesviruses, retroviruses, enteroviruses, and respiratory viruses, which have been associated with conditions such as dementia, multiple sclerosis, myelopathies, Guillain-Barré syndrome, and the post-acute neurologic sequelae of COVID-19. Furthermore, we discuss the role of neuroinflammation in viral-associated neurodegeneration and highlight emerging evidence supporting the recombinant zoster vaccine (Shingrix) as a potential modulator of neuroinflammatory processes and a protective factor against dementia. Conclusions: Cutaneous viral infections extend beyond local skin pathology, contributing to a broad spectrum of neurologic complications through intertwined infectious and inflammatory mechanisms. A clearer understanding of how peripheral viral activity shapes central nervous system vulnerability remains a major unmet need. A multidisciplinary approach integrating dermatologic and neurologic perspectives is essential for early recognition and prevention. While observational studies suggest that zoster vaccination may reduce viral reactivation and modulate neuroinflammatory pathways, definitive evidence of neuroprotection is still lacking. Future studies should clarify causal relationships, test mechanistic hypotheses regarding skin–brain immune crosstalk, and explore vaccine-mediated neuroprotection as a novel therapeutic strategy. Full article

Background: Long COVID (LC) is a multi-system disorder with persistent symptoms following SARS-CoV-2 infection. The presence of SARS-CoV-2 in the oral cavity and periodontium raises questions about its potential impact on periodontal health. Methods: A comprehensive literature search was conducted in PubMed using terms related to LC (e.g., “long-COVID,” “post-acute sequelae of SARS-CoV-2 infection,” “PASC,” “post-COVID-19,” “long-haul COVID”) and oral/periodontal diseases (e.g., “periodontal disease,” “periodontitis,” “gingiva,” “oral disease,” “dental”), filtered for English-language full-text articles published from 2019 to 2024. The search yielded 260 articles, which were supplemented with targeted searches on pathogenesis, immune mechanisms, microbiome alterations, and clinical outcomes, resulting in approximately 248 studies included in this review. Results: LC exhibits systemic immunoinflammatory dysregulation, including neutrophil activation, elevated pro-inflammatory cytokines, and complement activation, overlapping with mechanisms implicated in periodontitis. LC also leads to gastrointestinal and pulmonary dysbiosis, with potential effects on oral microbial communities. Gingival epithelium and periodontal ligament cells express ACE2, which is increased in periodontitis, facilitating viral entry. LC has been associated with reactivation of herpesviruses, such as Epstein–Barr virus, which are linked to autoimmune disorders and periodontitis. Conclusions: LC may act as a systemic risk factor for periodontitis. This review provides the theoretical foundation for the interactions between LC and oral health and highlights priorities for future epidemiologic and mechanistic research to better understand these relationships. Full article

Donkeys (Equus asinus) play a critical role in agricultural, transport, and livelihood systems across Asia, yet they remain among the most neglected domestic species in terms of welfare, management, and research attention. This review synthesizes recent literature on donkey welfare, health, breeding, and conservation across Asia, highlighting regional disparities and emerging challenges. A systematic review of published studies identified welfare determinants including nutrition, workload, shelter, and veterinary access. Welfare conditions are found to be poorest in South Asia, particularly in Pakistan, India, and Afghanistan, where chronic undernutrition, inadequate housing, excessive workloads, and limited veterinary support prevail. Preventive healthcare, such as vaccination and deworming, remains largely absent, reflecting low owner awareness and weak veterinary infrastructure. In contrast, China demonstrates substantial progress through semi-intensive farming systems, structured welfare management, and research-based breeding programs that integrate welfare with productivity enhancement. Recent advancements in molecular genetics have further expanded the scope of donkey conservation and improvement. Studies on key genes, including PRKG2, NR6A1, LTBP2, HOXC8, and DCAF7, have elucidated their roles in vertebral number, skeletal development, and body conformation in Dezhou donkeys, offering new opportunities for genomic-level conservation and marker-assisted selection. Nonetheless, significant health challenges, such as parasitic, bacterial, and viral infections (Theileria equi, Giardia duodenalis, and Equid herpesviruses), continue to threaten productivity and welfare. Reproductive management across most Asian countries remains traditional and uncoordinated, whereas China leads in artificial insemination, genetic resource preservation, and policy-supported breeding initiatives. Ethical concerns surrounding overexploitation and the commercial use of donkeys, particularly in the ejiao (donkey-hide gelatin) industry, are also gaining attention. Overall, this review underscores the urgent need for a “One Welfare” approach, linking Animal Welfare, human livelihoods, and sustainable industry development. Strengthening veterinary infrastructure, promoting owner education, and integrating genomic tools into breeding programs are essential steps toward improving the welfare, productivity, and long-term conservation of donkeys across Asia. Full article

Procellariiformes are among the most threatened seabirds globally, yet viral pathogens affecting this group remain poorly understood. Herpesviruses are widespread in birds and capable of establishing latency, reactivating under immunosuppression, and causing severe disease, particularly in cross-species transmission. We surveyed herpesvirus in 50 individuals (12 species) that stranded along the southeastern Brazilian coast (2017–2023). A nested pan-PCR protocol targeting the DNA polymerase gene detected herpesvirus DNA in 24% (12/50) of the birds. Seven distinct herpesvirus sequence types were identified, all clustering within the genus Mardivirus, including two previously known variants and novel lineages. To our best knowledge, this represents the first herpesvirus report in the Black-browed Albatross (Thalassarche melanophris), Cape Verde Shearwater (Calonectris edwardsii), Manx Shearwater (Puffinus puffinus), and Southern Giant-Petrel (Macronectes giganteus), as well as new host reports for the Yellow-nosed Albatross (T. chlororhynchos) and Cory’s Shearwater (C. borealis). No associated lesions were observed in histopathology. Our findings expand the known host range of herpesviruses in Procellariiformes and reveal possible circulation among colonies and non-breeding areas across the Southern and Northern hemispheres. Our results underscore the need for integrative ecological-, virological-, and population-based studies to clarify how seabird ecology influences herpesvirus transmission dynamics and long-term persistence in this group. Full article

Kaposi’s sarcoma (KS), an AIDS-defining illness, is caused by Kaposi’s sarcoma-associated herpesvirus (KSHV). A member of the human herpesvirus family, designated as human herpesvirus 8 (HHV-8), KSHV is also linked to other oncogenic manifestations such as primary effusion lymphoma (PEL). The current dearth of available compounds against KSHV necessitates development of effective antiviral treatments. As with other herpesviruses, KSHV can result in both lytic and latent infections. KSHV pathogenesis and the development of KS have been associated with the expression of KSHV genes and transcripts during viral infections. The transcriptome of KSHV heavily intersects with regulatory pathways and mechanisms involved with a multitude of diseases in humans. Circular RNAs (circRNAs) have recently been discovered to be expressed by KSHV. Research endeavors on KSHV circRNAs have focused on the roles they play throughout latent and lytic infection. Understanding the specific functions and interactions of KSHV circRNAs with the viral and host transcriptomes, as well as how they are identified and analyzed, will be the primary focus of this review. Overall, recent advances in KSHV circRNA research have deepened our understanding of the KSHV transcriptome and pathogenesis and are paving the way for the development of circRNA-based antiviral therapies. Full article

Oncogenic viruses are well-established contributors to cancer development in both humans and animals. While many animal oncogenic viruses exhibit strong host specificity, concerns remain about their potential to cross species barriers and impact human health. This article examines the classification and molecular mechanisms of oncogenic viruses, including retroviruses, papillomaviruses, herpesviruses, and hepadnaviruses, in animals. It explores historical cases of cross-species transmission, such as the contamination of early polio vaccines with simian virus 40 (SV40), which resulted from the use of rhesus monkey kidney cells and insufficient screening for latent simian viruses, and the hypothesised association between bovine leukaemia virus (BLV) and human breast cancer. To provide a broader comparative perspective, the discussion also includes examples of viruses with a lower economic impact, illustrating that zoonotic and oncogenic potential is not limited to commercially significant species. Biological barriers—including receptor specificity and immune defences—generally limit transmission; however, frequent human–animal interactions, consumption of contaminated food, and viral mutations may increase zoonotic risk. Advances in molecular diagnostics, such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and serological testing, play a critical role in identifying emerging threats. Prevention strategies, including veterinary vaccination programs, biosafety protocols, and the One Health approach integrating human and veterinary medicine, are essential for mitigating risks. While current evidence indicates that oncogenic animal viruses do not significantly contribute to human cancers, ongoing surveillance and research remain crucial to detect emerging threats. Understanding viral oncogenesis in animals continues to provide valuable insights into cancer prevention and therapy in humans. Full article

Polyomaviruses (BKPyV and JCPyV) and herpesviruses (EBV, CMV) usually infect people during childhood, and may be associated, in some clinical states, with immunocompromised individuals. The aim of this study was to investigate the occurrence and coexistence of polyomavirus (BKPyV and JCPyV) and herpesvirus (CMV and EBV) DNAemia in pediatric hematology/oncology patients, including HCT recipients, and to assess the clinical relevance of polyomaviruses DNAemia. Whole blood samples of 99 children (including 71 patients undergoing HCT) were analyzed for the DNA of the herpes- and polyomaviruses. Co-existence of herpesvirus DNAemia was checked for the patients and clinically analyzed in detail, especially for those positive for BKPyV DNA. BKPyV DNAemia was detected in 15 (15.2%) patients, with viral loads ranging from 1.2 × 10³–1.7 × 10⁷ DNA IU/mL. No JCPyV DNA was detected in any of the samples. Coinfections with EBV or CMV DNAemia were observed in a subset of BKPyV-positive patients. BKPyV DNAemia was more frequent among children with leukemia and in those undergoing HCT. Our findings highlight the clinical associations between BKPyV and herpesvirus DNAemia in immunocompromised pediatric patients. Routine BKPyV DNA monitoring, alongside standard herpesvirus screening, may provide clinically valuable insights in high-risk pediatric cohorts, particularly those with hematologic malignancies and post-HCT status. Full article

Furin, a calcium-dependent serine endoprotease of the proprotein convertase family, plays a pivotal role in both physiological homeostasis and viral pathogenesis. By cleaving polybasic motifs within viral glycoproteins, furin enables the maturation of structural proteins essential for viral entry, fusion, and replication. This mechanism has been documented across a broad spectrum of human pathogens, including SARS-CoV-2, influenza virus, human immunodeficiency virus, human papilloma virus, hepatitis B virus, flaviviruses, herpesviruses, and paramyxoviruses, highlighting furin as a conserved molecular hub in host–virus interactions. Genetic variability within the FURIN gene further modulates infection outcomes. Several single-nucleotide polymorphisms (SNPs), such as rs6226 and rs1981458, are associated with altered COVID-19 severity, whereas variants like rs17514846 confer protection against human papilloma virus infection. Conversely, mutations predicted to reduce enzymatic activity have been linked to attenuated SARS-CoV-2 pathogenesis in certain populations. These findings underscore the importance of considering population genetics when evaluating viral susceptibility and disease progression. Despite advances, unresolved questions remain regarding furin’s non-canonical roles in viral life cycles, tissue-specific regulation, and interactions with other host proteases and immune modulators. Targeted inhibition of furin and related convertases represents a promising avenue for broad-spectrum antiviral interventions. Collectively, current evidence positions furin as a central node at the intersection of viral pathogenesis, host genetic variability, and translational therapeutic potential. Full article

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma (KS) and several lymphoproliferative diseases. As with all herpesviruses, KSHV replicates in a biphasic manner, with the establishment of a latent, persistent infection from which reactivation occurs, resulting in the completion of the temporal lytic replication cycle and production of infectious virions. Herein, we discuss the impact of KSHV lytic replication on the host cell nucleus and nuclear-related pathways. We highlight the dramatic remodelling of the nuclear architecture driven by the formation of viral replication and transcription centres (vRTCs), and the implications for sub-nuclear organelles, and how pathways involved in DNA damage, ribosomal biogenesis and epitranscriptomic regulation are disrupted or modified during KSHV replication. These changes foster an environment favourable for KSHV replication and may provide novel targets and strategies for therapeutic intervention. Full article