Search Results (2,597)

The X-linked TLR7 rs179008 T allele has been associated with altered antiviral immunity. Given their shared inflammatory pathways and higher pediatric mortality rates in Brazil during the pandemic, we investigated their association with multisystem inflammatory syndrome in children (MIS-C) together with Kawasaki disease (KS) following SARS-CoV-2 infection. A cross-sectional study (2021–2022) analyzed 73 hospitalized children (<13 years) with confirmed COVID-19. Genotyping for TLR7 rs179008, TLR8 (rs3764879, rs2407992), and TLR3 rs3775291 was performed via PCR and Sanger sequencing. MIS-C/KS cases were identified using CDC criteria, with severity classified by the need for ICU care. Statistical analysis included Fisher’s exact test and relative risk (RR) calculations. Hemizygous boys carrying the TLR7 T allele had a 1.87-fold higher risk of MIS-C/KS (p = 0.007) and a 1.75-fold increased risk of severe or critical outcomes. The T allele frequency was 2.6× higher in MIS-C/KS cases versus other COVID-19 presentations. All fatalities occurred in boys (3/8 MIS-C cases) with one T-allele carrier. No associations were found for TLR8 or TLR3 variants. The TLR7 rs179008 T allele is a potential genetic risk factor for severe post-COVID-19 inflammatory syndromes in boys, likely due to impaired immune signaling. These findings highlight its utility as a biomarker for risk stratification in pediatric populations. Full article

Herpes Simplex Virus (HSV) infections, caused primarily by HSV-1 and HSV-2, are among the most prevalent viral diseases worldwide, with recurrent manifestations that significantly affect quality of life. Therapeutic strategies include both topical and systemic interventions, each with distinct goals. This systematic review was conducted according to PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science (2005–2025) identified studies evaluating topical or systemic treatments for HSV. Eligible studies included randomized controlled trials and observational studies reporting validated clinical outcomes. Topical treatments, including acyclovir cream, docosanol, and newer formulations, primarily reduce lesion duration and alleviate local symptoms when applied early. These interventions have limited systemic absorption and generally do not influence recurrence frequency. Novel delivery methods and combination strategies, such as acyclovir–hydrocortisone formulations or photodynamic therapy, may enhance local efficacy and symptom control. Systemic Therapies: Systemic antivirals, such as acyclovir, valacyclovir, and famciclovir, target both lesion resolution and recurrence prevention. Evidence from randomized trials supports their use for episodic and suppressive therapy, including short-course, high-dose regimens that improve adherence while controlling symptoms. Systemic therapy is particularly indicated for recurrent, disseminated, or high-risk infections. Topical and systemic therapies serve complementary roles in HSV management. Topical agents are useful for localized or initial episodes, while systemic therapy addresses broader clinical objectives, including recurrence reduction. Future research should focus on mechanism-based therapies, novel delivery systems, and standardized outcome measures to guide personalized treatment strategies. Emerging therapies targeting viral latency, immune modulation, and gene-editing technologies hold promise for long-term suppression and personalized management of HSV infections. 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

Background: Host genetic factors significantly influence individual susceptibility to severe COVID-19, potentially explaining the observed disparities in clinical outcomes across populations. One of the key effectors in innate immunity and antiviral defense is the CD209 gene. This study explored the potential correlation of the CD209 gene SNP rs2287886 with diverse COVID-19 patient outcomes. Materials and Methods: A total of 176 patients (87 in the moderate group and 89 in the severe/critical/death group) were included in the study. Genotyping of patients was performed using the qPCR methodology, through the TAQMAN system. The results were analyzed adopting a significance level of p < 0.05. Results: The GG genotype (compared to AG + AA) and the G allele (compared to the A allele) of the rs2287886 SNP were significantly associated with an increased severity of COVID-19 (p = 0.0005 and p < 0.0001, respectively). The G allele was more frequent in individuals with more severe clinical outcomes (49.43% vs. 25.28%). Furthermore, expression quantitative trait loci (eQTL) analysis indicated that the GG genotype of rs2287886 is associated with higher CD209 gene expression. Furthermore, the observed interaction analysis suggests that the interactions between CD209 and its associated proteins may play a role in modulating the immune response. Conclusions: Our findings suggest that Brazilian patients homozygous for the GG genotype of the rs2287886 polymorphism in the CD209 gene may be at increased risk of severe COVID-19 in the Brazilian population and may act as a potential prognostic marker of disease severity. 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

Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, has inflicted substantial economic losses on the global swine industry. While the severity of infectious disease depends on the dynamic interplay between inoculum dose and host response, the molecular mechanism by which PDCoV dose modulates host immunity remains unclear. Hence, we systematically compared the transcriptomic changes in intestinal epithelial cells infected with different doses of PDCoV, and investigated the relationships between inoculum dose, host immune responses, and disease progression. PDCoV replication peaked at 24 h post-infection, and host responses showed a distinct dose-dependent pattern, with high-dose infection inducing more extensive transcriptional remodeling than low-dose infection. Both doses significantly activated the transcription of STAT1 and its downstream interferon-stimulated genes, while high-dose infection additionally triggered a cytokine storm characterized by excessive IL-6 and TNF-α expression. Functional validation demonstrated that STAT1 overexpression markedly inhibited PDCoV infection by enhancing ISRE promoter activity, and overexpression of its downstream ISG15 and MX2 also exerted independent and significant antiviral effects. These findings reveal the biphasic nature of PDCoV dose-dependent regulation of immunopathological mechanisms and identify STAT1 and specific ISGs (ISG15, MX2) as potent antiviral effectors, providing crucial insights into PDCoV pathogenicity and offering promising targets for developing immunomodulatory therapeutics or vaccines to control PDCoV outbreaks in swine. Full article

Background/Objectives: The African swine fever virus (ASFV) multi-gene family (MGF) 360 proteins play critical roles in immune evasion, replication regulation, and virulence determination. Despite substantial advances in this field, the functional roles of many members within this gene family remain to be fully characterized. Methods: In this study, Transcriptional kinetics analysis indicated that the expression profile of MGF 360-2L was consistent with that of the late marker gene B646L (p72). Transcriptomic profiling identified 13 and 171 differentially expressed genes (DEGs) at 12 and 24 h post-infection (hpi) with ΔMGF 360-2L, respectively. Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that these DEGs were predominantly enriched in Type I interferon (IFN-I) signaling pathways. It is noteworthy that transcriptome analysis further demonstrates that the absence of MGF 360-2L specifically results in the dysregulation of expression of the replication-essential genes E199L and E301R. These findings indicate that MG F360-2L is essential for maintaining the stable expression of these proteins. Conclusions:MGF 360-2L is a late gene that contributes to the precise regulation of viral protein expression and modulates the host immune response during infection. Full article

Type 1 interferons (IFN-Is) exhibit significant antiviral, antitumor, and immunoregulatory properties, demonstrating substantial therapeutic potential. However, IFN-Is are pleiotropic cytokines, and the available data on their effect under specific pathological conditions are inconclusive. Furthermore, the systemic administration of IFN-Is can result in side effects. Generating cells that can migrate to the pathological focus and provide regulated local production of IFN-Is could overcome this limitation and provide a model for an in-depth analysis of the biological and therapeutic effects of IFN-Is. Induced pluripotent stem cells (iPSCs) are a valuable source of various differentiated cell types, including human immune cells. In this study, we describe the generation of genetically modified human iPSCs with doxycycline-controlled overexpression of interferon β (IFNB1). Three IFNB1-overexpressing iPSC lines (IFNB-iPSCs) and one control line expressing the transactivator M2rtTA (TA-iPSCs) were generated using the CRISPR/Cas9 technology. The pluripotency of the generated cell lines has been confirmed by the following: (i) cell morphology; (ii) the expression of the pluripotency markers OCT4, SOX2, TRA 1-60, and NANOG; and (iii) the ability to spontaneously differentiate into the derivatives of the three germ layers. Upon the addition of doxycycline, all IFNB-iPSCs upregulated IFNB1 expression at RNA (depending on the iPSC line, 126-816-fold) and protein levels. The IFNB-iPSCs and TA-iPSCs generated here represent a valuable cellular model for studying the effects of IFN-β on the activity and differentiation trajectories of different cell types, as well as for generating different types of cells with controllable IFN-β expression. 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

Sindbis virus (SINV), a prototype of the Alphavirus genus (family Togaviridae), is a globally distributed arbovirus causing febrile rash and debilitating arthritis in humans. Viral structural proteins—capsid (C), E1, and E2—are fundamental to the virion’s architecture, mediating all stages from assembly to host cell entry and pathogenesis, thus representing critical targets for study. This review consolidates the historical and current understanding of SINV structural biology, tracing progress from early microscopy to recent high-resolution cryo-electron microscopy (cryo-EM) and X-ray crystallography. We detail the virion’s precise T = 4 icosahedral architecture, composed of a nucleocapsid core and an outer glycoprotein shell. Key functional roles tied to protein structure are examined: the capsid’s dual capacity as a serine protease and an RNA-packaging scaffold that interacts with the E2 cytoplasmic tail; the E1 glycoprotein’s function as a class II fusion protein driving membrane fusion; and the E2 glycoprotein’s primary role in receptor binding, which dictates cellular tropism and serves as the main antigenic target. Furthermore, we connect these molecular structures to viral evolution and disease, analyzing how genetic variation among SINV genotypes, particularly in the E2 gene, influences host adaptation, immune evasion, and the clinical expression of arthritogenic and neurovirulent disease. In conclusion, the wealth of structural data on SINV offers a powerful paradigm for understanding alphavirus biology. However, critical gaps persist, including the high-resolution visualization of dynamic conformational states during viral entry and the specific molecular determinants of chronic disease. Addressing these challenges through integrative structural and functional studies is paramount. Such knowledge will be indispensable for the rational design of next-generation antiviral therapies and broadly protective vaccines against the ongoing threat posed by SINV and related pathogenic alphaviruses. Full article

The development of vaccines against many infectious diseases has been a great success of medical science over the last century. However, despite numerous efforts, effective vaccines for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) remain elusive. Since 1920s, a range of therapeutic vaccine candidates, primarily focusing on neutralizing antibodies, have failed to confer robust and durable protective immunity against recurrent herpes. Recent advances in omics, artificial intelligence, and deep learning have opened new horizons for the rational design of tissue-targeted herpes vaccine strategies for inducing potent and durable HSV-specific CD4⁺ and CD8⁺ T_RM cell immunity at both the sensory ganglia (central immunity), the site of latency/reactivation cycle, and the mucocutaneous epithelial tissues (peripheral immunity), the site of viral replication that causes herpetic lesions. Prime/Pull/Keep ocular and genital herpes vaccine candidates (PPK vaccines) have recently shown success in pre-clinical animal model trials of recurrent ocular and genital herpes. These PPK vaccines used “asymptomatic” epitopes/antigens to prime CD4⁺ and CD8⁺ T cells (Prime); primed T cells are then pulled towards the infected central and peripheral epithelial tissues using T cell-attracting chemokines, such as CXCL11 (Pull), followed by survival cytokines (IL-2, IL-7 and/or IL-15) or mucosal chemokines (CXCL17 and/or CCL28) to maintain the “pulled” tissue-resident T cells longer within infected tissues (Keep). We discuss recent efforts in designing a clinically adapted, all-in-one PPK mucosal therapeutic vaccine that would require a single administration to sequentially trigger all three PPK steps of priming, recruiting, and maintaining antiviral, tissue-resident, protective T cells at the primary sites of viral entry and latency. Full article

Hepatitis B virus (HBV) remains a major global health challenge, with over 296 million people chronically infected worldwide. Despite the availability of antiviral therapies, a functional cure is rarely achieved, highlighting the need for novel therapeutic strategies. RNA 5-methylcytosine (m⁵C) is a pivotal epitranscriptomic mark implicated in RNA stability, transport, and translation. Emerging evidence shows that m⁵C is conserved within HBV RNA and plays critical roles in the viral life cycle. This review provides a comprehensive overview of the molecular mechanisms governing m⁵C deposition and recognition, summarizes recent advances in m⁵C biology, and highlights the emerging role of epitranscriptomic m⁵C regulation in HBV infection. We discuss the identification of HBV-specific m⁵C sites, the functions of key regulatory enzymes, and their interplay in viral RNA stabilization and evasion of innate immune responses. Interplay between m⁵C and other RNA modifications—particularly N6-methyladenosine (m⁶A)—is examined alongside virus-specific m⁵C regulation in EV71, HIV, HCV, EBV, and SARS-CoV-2. Potential links between m⁵C dysregulation and HBV-induced hepatocarcinogenesis are outlined, and emerging therapeutic strategies targeting the m⁵C machinery are highlighted. Together, these insights position the epitranscriptomic landscape as a promising avenue for innovative antiviral strategies. Full article

Nuclear factors of activated T cells (NFATs) are pivotal regulatory factors of immune responses, primarily by modulating T cell activity and regulating inflammatory cytokine gene transcription. The grass carp reovirus (GCRV) triggers a serious hemorrhagic condition, posing a significant threat to sustainable grass carp (Ctenopharyngodon idella) aquaculture. However, the precise function of NFAT in the host’s defense against GCRV infection is mostly undefined. This study comprehensively identified and characterized the NFAT genetic family in grass carp, cloned grass carp NFAT1 (CiNFAT1), and investigated its expression and function during GCRV infection. Eight NFAT genes encoding seventeen isoforms have been detected within the grass carp’s genomic sequence, distributed across six different chromosomes. Comparative analysis revealed homology with zebrafish NFATs. CiNFAT1 possesses a 2697 bp open reading frame, encoding 898 amino acids, and contains conserved Rel homology domain (RHD) and NFAT-homology (IPT) domains. Quantitative PCR (qPCR) revealed ubiquitous CiNFAT1 expression in healthy grass carp tissues, with the highest expression in gills and skin and the lowest in liver. Following GCRV challenge in vivo, CiNFAT1 expression in immune tissues (liver, spleen, kidney, gill, intestine) showed dynamic changes over time. In vitro experiments in CIK cells demonstrated that CiNFAT1 expression peaked at 12 h post-GCRV infection. Further functional studies revealed that overexpression of CiNFAT1 significantly reduced GCRV replication at 36 h post-infection. This reduction was accompanied by elevated expression of type I interferon (IFN-I) and interferon regulatory factor 7 (IRF7) at 24 and 36 h, respectively, as well as modulated IL-2, IL-8, and IL-10. Conversely, RNA interference-mediated knockdown of CiNFAT1 enhanced GCRV VP5 and VP7 mRNA levels and suppressed IL-2 and IL-8 expression. These results suggest that CiNFAT1 contributes to anti-GCRV immunity by promoting antiviral and inflammatory cytokine responses, thereby inhibiting viral replication. This study provides a foundational understanding of the NFAT genetic family in grass carp and highlights an important role of CiNFAT1 in mediating the body’s inherent defense mechanism against GCRV infection, offering insights for disease control strategies in aquaculture. Full article

Poly (I:C), a viral mimic, is capable of activating the antiviral immune mechanisms in teleosts. In this study, we investigated the transcriptional responses of Ussuri Catfish (Pseudobagrus ussuriensis) to poly (I:C) stimulation at 3 and 48 h, focusing on the similarities and differences in antiviral mechanisms exhibited in the liver and spleen. At 3 h, the signaling pathways that were concurrently enriched in both the spleen and liver include JAK-STAT, TNF, NF-κB, RIG-I-like receptor, and NOD-like receptor. At 48 h, the signaling pathways that were concurrently enriched in both the spleen and liver include JAK-STAT signaling and cellular homeostasis processes. However, in the liver, the signaling pathways that responded to poly (I:C) stimulation at both 3 and 48 h are cytokine–cytokine receptor interaction and RIG-I-like receptor signaling. In the spleen, the signaling pathways that responded to poly (I:C) stimulation at both 3 and 48 h are Hippo signaling, Wnt signaling, TGF-β signaling, and ECM-receptor interaction. Ultimately, the pathways that were enriched in the intersection genes across all groups are JAK-STAT signaling, NK cell-mediated cytotoxicity, and ECM-receptor interaction, and the core genes identified in the intersection genes of all groups are PTPRS, HECW1, and ERN1 (IRE1), along with UMAD, DKK1, CSH, and RTKN2. Through this study, we identified the key signaling pathways and core genes involved in the antiviral response of Ussuri catfish. These findings provide valuable insights into the antiviral mechanisms of Ussuri catfish. Full article

Chronic hepatitis delta (CHD) represents the most severe form of viral hepatitis due to rapid disease progression towards liver cancer, leading to high morbidity and mortality. Hepatitis delta virus (HDV) can only infect individuals who are infected with hepatitis B. So far, there is no cure or vaccine for HDV. Existing treatment options, including pegylated interferon-α and hepatocyte entry inhibitors, offer limited efficacy. Emerging therapeutic strategies are focused on targeting various steps of the HDV life cycle or enhancing the host immune response to promote viral elimination. A defective antiviral immune response is increasingly recognized as a culprit for HDV persistence; however, the precise immunological mechanism associated with disease progression and pathogenesis has not been well defined. This review provides an update on the current understanding of host immune response in CHD, highlighting its role in both disease pathogenesis and viral clearance. A deeper understanding of these immune correlates may lead the way to novel treatment strategies, including immunotherapies targeting host immune response that can be used in combination with other antiviral therapies to achieve more effective and durable treatment outcomes. Full article