Search Results (9,793)

Chili pepper (Capsicum annuum L.) is an economically important crop in Mexico, with a production that is limited by viral diseases caused by Begomovirus infections such as PHYVV and PepGMV, both transmitted by Bemisia tabaci. These viruses affect both domesticated cultivars and wild populations. The use of resistant genotypes is the most effective strategy to reduce Begomovirus incidence. Since no commercial cultivars with resistance are currently available, in this study, 15 Capsicum annuum accessions with different levels of domestication were inoculated separately with infectious PepGMV and PHYVV dimers by bioballistics, in order to identify sources of genetic resistance or tolerance to these viruses. Symptom progression (severity), incidence, the area under the disease progress curve (AUDPC), and molecular detection of viral DNA by PCR were recorded in asymptomatic plants. PCR results with oligonucleotides targeting PepGMV and PHYVV showed that 96% of asymptomatic plants were positive, confirming that viral replication occurred without the development of visible symptoms. Significant differences were observed among accessions, with wild and semidomesticated accessions showing very low values of severity, incidence, and AUDPC. Notably, the wild accession Acc-106 exhibited resistance to PepGMV and tolerance to PHYVV, with minimum values of severity (0 and 0.13) and incidence (0% and 13%) at 35 days postinoculation. Full article

Background: Ecuador presents a unique epidemiological laboratory for studying arboviral dynamics due to its diverse ecological zones and exposure to climatic variability. Methods: We conducted a comprehensive 36-year analysis (1988–2024) of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) using national surveillance data from Ecuador’s Ministry of Public Health. Statistical analyses included time series decomposition, change-point detection, correlation analysis, and climate association studies. Results: Ecuador reported 387,543 arboviral cases, with dengue comprising 91.3% (353,782 cases). Dengue exhibited endemic–epidemic cycles with major peaks during El Niño events (1994: 10,247 cases; 2000: 22,937 cases; 2015: 42,483 cases; 2024: 23,156 cases through week 26). CHIKV emerged explosively in 2015 (29,124 cases, incidence 181.10 per 100,000), followed by ZIKV in 2016 (2947 cases). Both showed rapid decline post-epidemic. Severe dengue cases paradoxically decreased from 2–4% of total cases in early 2000s to <0.1% post-2016, suggesting immunological modulation. Cross-correlation analysis revealed significant associations between climatic indices and epidemic timing ($r=0.67$, $p<0.001$), particularly for the El Niño-Southern Oscillation. Conclusions: Arboviral diseases in Ecuador function as an integrated epidemiological system with evidence of viral interactions, cross-protective immunity, and strong climate forcing. These findings emphasize the need for integrated surveillance and adaptive control strategies. Full article

Penaeus vannamei aquaculture production accounts for the majority of total shrimp aquaculture output, but it has suffered a severe decline in production and economic losses due to WSSV disease. Therefore, elucidating the relationship between the host immune system and pathogens is crucial for shrimp disease prevention and control. Integrins, as receptor-related molecules, have been shown to participate in various physiological functions, including cell migration, organismal development, and the pathogenesis of multiple diseases. However, the regulatory mechanisms of integrin genes in the shrimp immune system remain unclear. This study reports that integrins may regulate the Toll, IMD, and STAT signaling pathways in P. vannamei by influencing Spätzle, TLR, and Domeless, thereby affecting the shrimp’s innate immune system against diseases. Additionally, integrins can inhibit viral entry and replication. Through RNA interference (RNAi) experiments, it was found that knocking down Pv-Integrin β increases the viral load of white spot syndrome virus (WSSV), making shrimp more susceptible to WSSV and giving rise to increasing mortality. Further research indicates that Pv-Integrin β acts as an upstream recognition receptor in the disease resistance immune pathway, influencing other signaling pathway receptors to regulate the innate immune system. Importantly, knocking down Pv-Integrin β upregulates the expression of antimicrobial peptides such as ALF1 and ALF2, but reduces the expression of Crustin1, Crustin2 and prophenoloxidase. In conclusion, this study reveals that Pv-Integrin β regulates the disease resistance immune signaling pathways by affecting the related receptors. Full article

Myocardial infarction-induced cardiovascular diseases remain a leading cause of mortality worldwide. Excessive post-infarct fibrosis contributes to adverse cardiac remodeling and the progression to heart failure. In vivo reprogramming strategies offer a promising avenue for heart regeneration by directly converting resident fibroblasts into cardiomyocytes through enforced expression of cardiogenic genes. This approach circumvents the need for invasive biopsies, cell expansion, induction of pluripotency, or autologous transplantation. Despite these advantages, key challenges persist, including low reprogramming efficiency and limited cellular targeting specificity. A critical factor for effective anti-fibrotic therapy is the precise and efficient delivery of reprogramming effectors specifically to fibrotic fibroblasts, while minimizing off-target effects on non-fibroblast cardiac cells and fibroblasts in non-cardiac tissues. In this review, we discuss the cellular and molecular mechanisms underlying in vivo cardiac reprogramming, with a focus on fibroblast heterogeneity, key transcriptional drivers, and relevant intercellular interactions. We also examine current advances in fibroblast-specific delivery systems employing both viral and non-viral vectors for the administration of lineage-reprogramming factors such as cDNA overexpressions or microRNAs. Finally, we underscore innovative strategies that hold promise for enhancing the precision and efficacy of cellular reprogramming, ultimately fostering translational development and paving the way for rigorous preclinical assessment. Full article

Newcastle Disease (ND) is an important and notable disease among the avian infectious diseases, because of its high contagiousness, and the most virulent strains of ND virus (NDV) have impacted poultry breeders all over the world. Immunization and biosecurity measures are used to reduce ND; however, vaccination has been shown to offer protection against clinical signs but not against virus proliferation and shedding, which could have an adverse effect on the environment. The genetic basis for inherent resistance to NDV has been established, and genetic selection on existing resistance-related genetic variation can help to mitigate virus propagation. Further, understanding the genes and processes that drive the response to NDV will lay the groundwork for genetic improvement in poultry. The majority of studies on NDV susceptibility make use of phenotypic indicators such as body weight, morbidity, mortality, antibody response, and viral load. According to recent advancements in molecular genetic research, many different genes are diversely regulated in different chicken lines to NDV infection, which might be used in the future to establish disease-resistant breeding approaches. It is possible that many more genes linked to illness and resistance are still to be discovered, because the precise mechanism of resistance is not entirely understood. The enhanced genetic knowledge of chickens and the development of more advanced transgenic techniques would lead to pathogen resistance. Hence, this paper summarizes the current understanding of genetic resistance to Newcastle Disease, and we additionally highlight a few possible genes/markers connected with NDV that may improve chicken resistance to NDV infections and can be used to produce NDV-resistant chicken breeds/strains in the near future. Full article

Influenza virus is a leading cause of global morbidity and mortality due to acute lower respiratory infection, even with the widespread use of multiple licensed influenza vaccines. However, antigenic drift during influenza replication can cause vaccine-induced antibodies to poorly neutralize influenza virus, thereby reducing vaccine effectiveness. To help overcome this problem, we leveraged a hydrogel platform with influenza hemagglutinin (HA) protein to induce prolonged antigen exposure. The hydrogel platform, Vaccine Self-Assembling Immune Matrix (VacSIM^®), in combination with recombinant influenza H1 or H3 HA protein antigens, increased antigen-specific antibody titers in vaccinated mice, which led to decreased disease severity after H1N1 infection for H1 HA-vaccinated mice and decreased lung viral titers after H3N2 challenge for H3 HA-vaccinated mice. Sera collected from mice immunized with VacSIM and HA also showed broader HAI activity, increasing by 1–3 log against a panel of influenza viruses. These results were consistent with the use of cocktail immunization, containing both an H1 and H3 HA, where mice immunized with VacSIM had an increase in antigen-specific antibody titers and decreased disease severity and lung viral titers against H1N1 and H3N2 influenza challenges, respectively. Finally, it was determined that a single immunization with VacSIM and H1 HA could provide protection against lethal H1N1 challenge compared to a group without VacSIM. In summary, we demonstrate that use of the slow-release platform VacSIM can improve the host immune response to vaccination and increase protection against influenza infection. Full article

Bovine respiratory disease complex (BRDC) is a multifactorial and globally prevalent condition involving a combination of viral and bacterial pathogens, as well as environmental stressors. Viral agents often initiate infections in the upper respiratory tract (URT), predisposing animals to secondary bacterial infections and severe clinical manifestations. Among the key viral contributors to BRDC are bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BHV-1). In this study, submerged liquid cultures of undifferentiated bovine nasal epithelial cells (BNECs) were employed to investigate mono- and co-infections with BVDV and BHV-1. Epithelial barrier integrity was assessed to evaluate the cytopathic effects of BHV-1, while viral replication and release were quantified. Both viruses demonstrated polarized release, and BHV-1 infection exhibited a pronounced cytopathic effect. Notably, a preceding BVDV infection did not alter the progression or outcome of BHV-1 infection in this in vitro model. These findings suggest that primary BNEC cultures represent a valuable and physiologically relevant tool for studying viral dynamics and interactions associated with BRDC. Full article

During infectious disease outbreaks, acquiring genetic data across various kingdoms offers essential information to tailor precise treatment methodologies and bolster clinical, epidemiological, and public health awareness. Metagenomics sequencing has paved the way for personalized treatment approaches and streamlined the monitoring process for both co-infections and opportunistic infections. In this study, we conducted long-read metagenomic DNA sequencing on mpox-like lesion pustules from six suspected patients who were positive and confirmed to be infected with MPXV during the MPXV subclade Ib outbreak in the Eastern Democratic Republic of the Congo. The sequenced data were taxonomically classified as bacterial, fungal, and viral in composition. Our results show a wide spectrum of microorganisms present in the lesions. Bacteria such as Corynebacterium amycolatum, Gardnerella vaginalis, Enterococcus faecium, Enterobacter clocae, Staphylococcus epidermidis, and Stenotrophomonas maltophilia were found in the lesions. The viral classification of the reads pointed out the absolute predominance of the monkeypox virus. Taken together, the outcomes of this investigation underscore the potential involvement of microorganisms in mpox lesions and the possible role that co-infections played in exacerbating disease severity and transmission during the MPXV subclade Ib outbreak. Full article

The aggregation of α-synuclein (αSyn) is a central feature of Parkinson’s disease (PD) and other synucleinopathies. The efficient clearance of αSyn depends largely on the autophagy–lysosomal pathway. Emerging genetic evidence highlights the role of pleckstrin homology and RUN domain-containing M1 protein (PLEKHM1), a critical regulator of autophagosome–lysosome fusion, in the pathogenesis of multiple neurodegenerative diseases. This study investigates the possible effects of increased PLEKHM1 expression on αSyn pathology and neurodegeneration in mice. We utilized a mouse model of PD that is based on A53T-αSyn overexpression, achieved by the stereotactic injection of recombinant adeno-associated viral vectors (rAAV) into the substantia nigra. Additionally, this study explores the effect of PLEKHM1 overexpression on the autophagy–lysosomal pathway under physiological conditions, using transgenic autophagy reporter mice. PLEKHM1 overexpression facilitated the αSyn-induced degeneration of dopaminergic somata in the substantia nigra and degeneration of dopaminergic axon terminals in the striatum. In concert with αSyn expression, PLEKHM1 also potentiated microglial activation. The extent of αSyn pathology, as reported by staining for phosphorylated αSyn, was not affected by PLEKHM1. Using RFP-EGFP-LC3 autophagy reporter mice, rAAV-mediated PLEKHM1 overexpression reduced lysosomal and autolysosomal area, increased LAMP1-LC3 colocalization, and decreased the autolysosome-to-autophagosome ratio. Concurrently, PLEKHM1 overexpression in both genotypes caused p62 accumulation, accompanied by reduced overlap with lysosomal and autophagosomal markers but increased colocalization with autolysosomal markers, indicating impaired cargo degradation during late-stage autophagy. Taken together, elevated PLEKHM1 levels exacerbate neurodegeneration in αSyn-overexpressing mice, possibly by impairing autophagic flux. Now, with in vivo evidence complementing genetic data, alterations in PLEKHM1 expression appear to compromise autophagy, potentially enhancing neuronal vulnerability to secondary insults like αSyn pathology. Full article

Interleukin-24 (IL-24) is a cytokine known for its role in immune regulation and apoptosis, with potential implications in viral infections like COVID-19. This study aimed to investigate the association between IL-24 serum levels and the severity of COVID-19 disease. In this prospective bi-center cross-sectional study, we enrolled 41 COVID-19 patients from two hospitals in Germany. Serial blood samples were collected from a subset of patients, resulting in 88 total blood samples. Patients were categorized into critical, severe, moderate, and mild disease groups based on WHO criteria. IL-24 serum levels were measured during the acute or convalescent phase using an ELISA assay. Inflammatory markers, and kidney and liver function parameters were also evaluated. Statistical analysis included non-parametric tests and correlation analysis. Elevated IL-24 serum levels were observed in ambulant patients (mild disease), compared to hospitalized patients (critical, severe, moderate disease, p < 0.05). IL-24 levels were also significantly higher in patients without oxygenation disorder compared to those with oxygenation therapy (p < 0.05). A negative correlation was found between IL-24 levels and markers of inflammation and liver/kidney function. Elevated IL-24 serum levels were associated with milder COVID-19 courses, suggesting a protective role in modulating immune responses and promoting antiviral apoptosis. Conversely, reduced IL-24 in severe cases may reflect impaired immune regulation, highlighting its potential as a biomarker and therapeutic target. Full article

Enteroviruses, a diverse genus within the Picornaviridae family, are responsible for a wide range of human infections, including hand, foot, and mouth disease, respiratory disease, aseptic meningitis, encephalitis, myocarditis, and acute flaccid paralysis. Despite their substantial global health burden and the frequent emergence of outbreaks, no specific antiviral therapies are currently approved for clinical use against non-polio enteroviruses. This review provides a comprehensive overview of the current landscape of antiviral strategies targeting enteroviruses, including direct-acting antivirals such as capsid binders, protease inhibitors, and viral RNA polymerase inhibitors. We also examine the potential of host-targeting agents that interfere with virus–host interactions essential for replication. Emerging strategies such as immunotherapeutic approaches, RNA interference, CRISPR-based antivirals, and peptide-based antivirals are also explored. Furthermore, we address key challenges, including viral diversity, drug resistance, and limitations in preclinical models. By highlighting recent advances and ongoing efforts in antiviral development, this review aims to guide future research and accelerate the discovery of effective therapies against enterovirus infections. Full article

The emergence of the SARS-CoV-2 JN.1 lineage in late 2023 marked a major shift in viral evolution. By January 2024, it had displaced XBB variants to become the dominant strain worldwide. JN.1 and its descendants are antigenically distinct from earlier Omicron subvariants, with approximately 30 additional spike mutations compared to XBB-derived viruses. The combination of these features alongside growing evidence of considerable immune evasion prompted the FDA to recommend that vaccine formulations be updated to target JN.1 rather than XBB.1.5. The continued dominance of JN.1-derived variants necessitates the characterization of viral infection in established animal models to inform vaccine efficacy and elucidate host–pathogen interactions driving disease outcomes. In this study, transgenic mice expressing human ACE2 were infected with SARS-CoV-2 subvariants JN.1, KP.2, and EG.5.1 to compare the pathogenicity of JN.1-lineage and XBB-lineage SARS-CoV-2 viruses. Infection with JN.1 and KP.2 resulted in attenuated disease, with animals exhibiting minimal clinical symptoms and no significant weight loss. In contrast, EG.5.1-infected mice exhibited rapid progression to severe clinical disease, substantial weight loss, and 100% mortality within 7 days of infection. All variants replicated effectively within the upper and lower respiratory tracts and caused significant lung pathology. Notably, EG.5.1 resulted in neuroinvasive infection with a significantly high viral burden in the brain. Additionally, EG.5.1 infection resulted in a significant increase in CD8⁺ T cell and CD11b⁺ CD11c⁺ dendritic cell populations in infected lungs. Full article

Vulvar viral infections such as condyloma acuminata, genital herpes, molluscum contagiosum, and Lipschütz ulcers span both sexually and non-sexually transmitted diseases and affect patients across all age groups. Lesions may present as papules, verrucous growths, or painful ulcers, often causing functional impairment and significant psychosocial distress. A multidisciplinary strategy that integrates epidemiology, precise diagnostics, individualized therapy, and psychological support is essential to optimize outcomes. We performed a structured literature search in PubMed, Scopus, and Web of Science using terms “vulvar viral infection,” “HPV,” “HSV,” “molluscum contagiosum,” and “Lipschütz ulcers.” International guidelines from the UK, Europe, and Australia were reviewed, alongside reference lists of key articles. Particular attention was given to paradoxical presentations, pediatric considerations, and cost-effectiveness analyses. HPV vaccination programs have markedly reduced anogenital warts, while early PCR/NAAT for HSV accelerates targeted antiviral therapy. First-line treatments like oral acyclovir/famciclovir for HSV and topical imiquimod or podophyllotoxin (±cryotherapy) for HPV are supported by adjunctive measures for self-limiting conditions. Host factors (hormonal cycles, immune status) and local irritants modulate recurrence risk, informing anticipatory suppressive regimens and barrier-reinforcing care. Validated patient-reported outcome measures (VPAQ, DLQI, FSFI) capture pain, sexual function, and quality-of-life impacts. Health–economic evaluations underscore the long-term value of rapid diagnostics and broad vaccination. Personalized, multidisciplinary management that combines prevention, precision diagnostics, tailored therapy, psychosocial support, and economic considerations offers the greatest promise for improving clinical and quality-of-life outcomes in patients with vulvar viral infections. We aim to outline best practices for the diagnosis and management of common vulvar viral infections, providing practical guidance for clinicians to improve recognition and therapeutic decision-making. Full article

Background and Objectives: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, and progressive arthritis is its primary clinical manifestation. The role of human parvovirus B19 (B19V) infection in the progression of RA remains unclear. This study aims to investigate the association between B19V infection and viral genetic distribution in Vietnamese RA patients. Materials and Methods: 115 Vietnamese RA patients and 86 healthy controls (HCs) were enrolled in this observational study at the Thai Nguyen National Hospital from January 2019 to December 2021. B19V DNA was examined in serum and synovial fluid samples from RA patients using nested PCR and real-time PCR. B19V antibodies were detected in serum samples using ELISA. Results: B19V DNA was detected in the serum of 2 out of 115 (1.74%) RA patients but not in any HCs. Interestingly, B19V DNA was present in 12 out of 68 (17.65%) RA patients with knee effusion in their synovial fluid. Anti-B19V-IgG and anti-B19V-IgM were detected in the serum of 42.61% and 2.61% of RA patients, respectively, and in 24.42% and 12.79% of HCs, respectively. Anti-B19V-IgG levels were significantly higher in the serum of RA patients than in the serum of HCs (p = 0.007). However, anti-B19V-IgM was more commonly detected in HC serum than in RA patient serum (p = 0.006). Phylogenetic analysis showed that all B19V strains belonged to genotype 1 and subgenotype 1A. Conclusions: B19V infection is frequent in RA patients and suggests a contribution of B19V to the progression of RA, particularly in a B19V genotype-1- and subgenotype-1A-dependent manner and emphasises the need for early detection and management of B19V infection in RA patients. Full article

Background: The relationship between detectable circulating tumor DNA levels and clinical outcome following definitive therapy in patients with human papillomavirus (HPV)-mediated oropharyngeal squamous cell carcinoma has not been well established. Methods: In this retrospective analysis of patients with HPV-positive oropharyngeal squamous cell carcinoma seen from 2016 to 2024 at a single institution, 88 patients met inclusion criteria with baseline-positive tumor tissue-modified viral HPV DNA (TTMV-HPV DNA) testing and post-treatment testing performed. Results: Of the 88 patients included in the survival analysis, 77 had undetectable tumor tissue-modified viral human papillomavirus DNA after treatment, while 11 had positive (detectable) tumor tissue-modified viral human papillomavirus DNA. TTMV-HPV DNA positivity after treatment was associated with worse 1-year and 2-year overall survival outcomes, at 63.5% (37.7–100, p = 0.022) and 50.8% (25.7–100, p = 0.017) compared to 100% and 96.4% (91.6–100, p = 0.017) in patients with undetectable TTMV-HPV DNA. Inability to clear TTMV-HPV DNA after treatment was associated with worse progression-free survival, at 45.0% (95% CI 21.8–92.7, p = 0.009) at 1 year and 11.3% (95% CI 1.8–71.2, p = <0.001) at 2 years compared to 93% (95% CI 87.3–99.1) and 84.7% (95% CI, 76.3–94.0) in patients with cleared TTMV-HPV DNA after treatment. Conclusion: Tumor tissue-modified viral human papillomavirus DNA positivity after definitive treatment was associated with worse survival and disease recurrence outcomes compared to that in patients with undetectable post-treatment TTMV-HPV DNA. Prospective studies are warranted to further establish the clinical utility of TTMV-HPV DNA testing and its use in surveillance, treatment intensification, or de-intensification. Full article