The impact of physiological stress conditions on Kaposi's sarcoma-associated herpesvirus (KSHV) infection remains poorly understood. One such stressor, hypoxia, is regulated by the transcription factor HIF-1α. We recently reported that hypoxia, or HIF-1α expression alone, can promote lytic infection in cells that typically support latent infection under normoxia. Here, we show that hypoxia-induced lytic infection is reversible, leading to an abortive lytic cycle if the hypoxic condition ceases. Additionally, we found that HIF-1α induces lytic de novo infection only if expressed within the first 24 h post-infection (hpi). We show that HIF-1α can bind to viral promoters and induce lytic genes only during this early window of infection, before the KSHV genome undergoes heterochromatinization and establishes latency. In contrast, regardless of the timing of HIF-1α expression during KSHV infection, the induction of HIF-1α host target genes remains unaffected. These results indicate that the heterochromatinized KSHV DNA becomes resistant to HIF-1α-mediated activation after latency is established. These findings may explain why, despite the expression of HIF-1α in Kaposi's sarcoma tumors, KSHV remains in latency, because HIF-1α cannot induce lytic genes once the viral DNA is heterochromatinized. Importantly, we also demonstrate that inhibition of the epigenetic repressor PRC2, which associates with lytic promoters after 24 hpi, restores HIF-1α's ability to bind viral promoters and induce lytic gene expression post-latency. Collectively, our results indicate that not only the presence of HIF-1α, but also the timing and duration of its expression during KSHV infection, are critical determinants of its ability to drive lytic infection.IMPORTANCEThe current view is that the default pathway of KSHV infection is the establishment of latency, however, how this is altered under physiological stress conditions remains largely unknown. We previously showed that hypoxia, or the expression of its transcription factor HIF-1α alone, promotes the establishment of lytic rather than latent KSHV infection. In this study, we show that the duration of hypoxia, as well as the timing and duration of HIF-1α expression, are crucial determinants in facilitating lytic de novo KSHV infection. Notably, we found that PRC2-mediated heterochromatin inhibits the HIF-1α-mediated upregulation of lytic genes as chromatinization of the KSHV genome progresses during infection. Our findings offer a deeper understanding of how epigenetic regulation intersects with host stress responses to influence viral pathogenesis.

ABSTRACT Frequent outbreaks of eel “mucus sloughing and hemorrhagic septicemia disease” caused by Anguillid herpesvirus 1 (AngHV) are a major epidemic in both wild and farmed eels. This virus has garnered global attention due to heavy losses on eel farms and the lack of protective vaccines or effective drugs, highlighting the urgent need for potent antiviral agents. In this study, we revealed a hepcidin homolog LJ-hep2 from Japanese seabass (Lateolabrax japonicus) can bind to AngHV and impede viral entry into cells. LJ-hep2 could directly destroy the viral envelope and showed a higher anti-AngHV activity than AA-hep (a hepcidin homolog cloned from Anguilla anguilla). It was found that the destruction of viral structure by LJ-hep2 was related to the binding of the peptide to AngHV envelope protein ORF51, and the two amino acid residues at the N-terminus of the peptide (lysine and phenylalanine) might play a key role. Comparative antiviral experiments with mutated LJ-hep2 (LJ-hep2A4A5) and multi-species hepcidin further confirmed this finding and demonstrated that these two amino acids were indispensable in the inhibition of AngHV infection by LJ-hep2. In an established eel immersion infection model, LJ-hep2 treatment reduced viral accumulation in tissues, inhibited horizontal transmission, alleviated skin lesions, and improved eel survival. Taken together, this study suggests that LJ-hep2 could inhibit AngHV infection in vitro and in vivo, and identify ORF51 as a potential target for the development of anti-AngHV drugs.

Crocin (CRO) is an antioxidant carotenoid extracted from the Crocus sativus plant. CRO impacts many biological pathways related to inflammation, but its activity as an antioxidant and anti-inflammatory agent against ferritinophagy-associated oxidative damage and cell death in colonic mucosa is little understood. Therefore, this study predicted CRO-driven protective targets and processes against ulcerative colitis (UC) using network pharmacology, docking, and experimental analysis. Network analysis and molecular docking were used to analyze CRO and UC targets and pathways. To test the pharmacological efficacy of CRO invivo, 24 rats were separated into four groups: Cont, UC, mesalazine (100 mg/kg), and CRO (40 mg/kg). Rats received oral treatments for 8 days before UC induction. A single intrarectal injection of 2 mL acetic acid (AA) caused UC in rats. Estimated DAI and colonic protein content. Oxidant/antioxidant status and inflammatory markers ULK1, FTH-1, Beclin-1, GPX4, NCOA4, and SLC7A11 were also evaluated. Additionally, western blot was used to measure mTOR, AKT, and LC3B protein. Both histopathological and immunohistochemical studies were done. The network showed 228 CRO-UC targets, including CASP3 in the top 10 targets. AKT2 and MAP1LC3B were 56th and 63rd, respectively. The top 30 markedly enhanced KEGG pathways included "Pathways in cancer" and "Kaposi sarcoma-associated herpesvirus infection". Docking confirmed CRO's significant binding affinity for ULK1, FRIH, GPX4, and SLC7A11. Invivo, CRO pre-treatment diminished ULK1, autophagic proteins (Beclin-1 and LC3B-II/LC3B-I), and ferritinophagy-related protein (NCOA4), while elevating Akt/mTORC1, FTH-1, SLC7A11, and GPX4, thereby mitigating iron overload, ROS, and ferroptosis. Changing AKT/mTORC1/ULK1 pathway in UC pathogeneses improved colonic morphological and macroscopic abnormalities in CRO-treated rats. This study suggests that CRO may reduce ferritinophagy-induced colonic oxidative damage in rats via modulating AKT/mTORC1/ULK1. Ferritinophagy as an attractive therapeutic target in different experimental and clinical conditions deserves further investigation.

ABSTRACTAdaptive immune responses to primary Kaposi sarcoma-associated herpesvirus (KSHV) infection are poorly defined. To develop better small-animal models for understanding KSHV pathogenesis and immunity, we previously generated a chimeric virus in which the KSHV latency-associated nuclear antigen (kLANA), a conserved multifunctional protein critical for viral latency, was exchanged for the LANA homolog in murine gammaherpesvirus 68 (MHV68). Despite comparable levels of latent infection between WT and KLKI MHV68, kLANA directly repressed MHV68 lytic replication and reactivation. We therefore hypothesized that suppression of lytic replication by kLANA dampens adaptive immune responses. To test this, mice were infected with equivalent doses of either WT or KLKI MHV68 and adaptive immune responses were evaluated over time. B and T cell activation was starkly reduced following KLKI MHV68 infection, despite a potent virus-specific effector CD8+ T cell response against both viruses. These phenotypes were independent of inoculating dose, as high dose infection with KLKI MHV68 still showed reduced adaptive immune cell activation. In contrast, infection ofIfnar1-/-mice, which support enhanced KLKI MHV68 lytic replication, led to potent adaptive cellular and humoral immune activation by both WT and KLKI viruses, suggesting that the level of viral replication, and not simply amount of virus present, is a major driver of adaptive immunity during GHV infection. Collectively, these data support the hypothesis that kLANA-mediated suppression of lytic replication facilitates immune evasion by holding viral replication below a threshold for potent induction of adaptive immunity.IMPORTANCEKSHV is a gammaherpesvirus that establishes lifelong, chronic infections in humans and increases the risk of virus-associated cancers. Currently, there is little information on how primary KSHV infection influences adaptive immune development in healthy individuals. Rodent models, such as murine gammaherpesvirus 68 (MHV68), provide a valuable laboratory system for studying gammaherpesvirus pathogenesisin vivo. In this study, we report that infection with a previously characterized chimeric KSHV-MHV68 virus expressing KSHV LANA represses lytic viral replication and elicits weak antiviral adaptive immune responses following primary infection, despite efficient latency establishment. Using this chimeric MHV68 virus, we demonstrate that lytic viral amplification must breach a threshold to trigger a potent virus-specific adaptive immune response. We propose that KSHV, through LANA, evades detection by repressing lytic viral replication to remain “below the radar” of adaptive immune defenses during host colonization.

Gammaherpesvirus is a subfamily of herpesvirus, distinct phylogenetically from alpha- and betaherpesvirus and featured by its oncogenic subtypes, including Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus1. It broadly infects humans and other vertebrate animals and causes various diseases and malignancies2,3. However, no specific antiviral agents are available for each type or the whole family. gB is the common fusion protein vital for herpesvirus infection and an ideal target for broad vaccine development, while the lack of basis for gB as a universal antigen hinders such effort4. Here, we report the molecular basis for broad gB binding and cross-genus virus neutralization by an antibody Fab5 for the first time. This antibody confers effective protection against authentic virus challenges in immune-competent mice, non-human primates, and humanized mice with murine, rhesus, and human gammaherpesvirus. Cryo-EM structures revealed that Fab5 targeted a conservative and vulnerable epitope of gammaherpesvirus gB and antigenically exposed across pre- or post-fusion status. This finding not only demonstrates Fab5 as cross-genus antibody broadly reactive against gammaherpesvirus infection and pathogenesis progression, but offers insights into potential common mechanisms for herpesvirus infection and facilitates the development of broad-spectrum vaccines against the gammaherpesvirus.

Introduction: Maternal Toxoplasma, Rubella viruses, Cytomegalovirus, and Herpes viruses (TORCH) infections continue to be a challenge in obstetric practice since they can cause severe congenital abnormalities. Evaluating seroprevalence among pregnant women at a tertiary care facility helps identify immunity gaps and inform the development of appropriate screening procedures. Aim: To determine the pre-intervention serological status of expectant mothers undergoing maternal clinical visits for prenatal care. Materials and Methods: This cross-sectional study was conducted at the Department of Microbiology, Nootan Medical College and Research Centre, Sankalchand Patel University, Visnagar, Gujarat, India, from July 2023 to January 2025. A total of 249 pregnant women aged 18-41 years were enrolled through random sampling, and blood samples were taken after obtaining informed consent. Every participant had their antibody levels checked against TORCH using the Enzyme Linked Immunosorbent Assay (ELISA). Statistical analysis was done by parametric tests, such as Analysis of Variance (ANOVA) and non parametric tests, such as Chi-square, to compute p-value, correlation coefficient (r), and Phi/Cramer’s V. A p-value of <0.05 was considered statistically significant. Results: A total of 249 pregnant women were included in the study, with a mean age of 27 years and a range of 18 to 41 years. IgM was found in 31 (12.4%) and IgG in 244 (97.99%) out of the 249 (100%) samples. Toxoplasma gondii, Rubella virus, Cytomegalovirus (CMV), and Herpes 2 had IgM seropositivity of 4 (1.6%), 7 (2.8%), 11 (4.4%), and 11 (4.4%), respectively. In contrast, IgG antibodies to Herpes 1+2, Rubella, Toxoplasma gondii, and CMV were detected in 71 (28.5%), 133 (53.41%), 18 (7.3%), and 241 (96.78%) of the samples, respectively. Conclusion: Women who have more pregnancies are more likely to become infected with several agents, and Women tend to be seropositive to many agents than just one. So, prenatal screening for immunity and immunisation status is recommended for women of reproductive age.

Interleukin- 17A as an Immunomodulatory Cytokine in Animal Health and Diseases: A Systematic Review.

Synergistic effects of koi herpesvirus infection and nanoplastic exposure on the physiological and immune responses of koi carp.

Autoantibodies (autoAbs) neutralizing type I interferons (IFN-I) markedly increase the risk of severe manifestations of some viral diseases. The prevalence of autoAbs neutralizing at least one IFN-I, specifically IFN-α2, IFN-β, and IFN-ω, in individuals from the Swiss human immunodeficiency virus 1 (HIV-1) cohort is largely similar to French age-matched healthy controls, with around 1% in adults by age 65 having neutralizing IFN-I autoAbs and rising thereafter. We analyzed samples from Danish individuals with HIV, including antiretroviral therapy (ART) treated (n = 260) and ART-naive (n = 58) individuals, aged 18-79 (mean age 46.6 years, SD ± 11.1 years), and American individuals with HIV, all of whom were ART-naive (n = 292) aged 20-76 (mean age 41.7 years, SD ± 10.1 years). In the Danish cohort, a total of 2/318 (0.63%) individuals had autoAbs neutralizing 1 ng/ml IFN-ω, whereas 1/318 (0.31%) had autoAbs neutralizing 200 pg/ml IFN-ω. In the American cohort, 2/292 (0.68%) individuals had autoAbs neutralizing IFN-ω at 1 ng/ml. Combining both cohorts, the overall prevalence of autoAbs neutralizing IFN-ω was 5/610 (0.82%). Longitudinal samples were available for two individuals with IFN-ω autoAbs: One displayed persistently detectable autoAbs over time, whereas the other showed a decline in neutralizing activity after 2 years. Two out of five individuals with IFN-I neutralizing autoAbs had a history of IFN-α treatment for chronic hepatitis C virus (HCV) infection. Individuals with IFN-I neutralizing autoAbs shared a history of viral infections, including mucocutaneous herpesvirus infections, zoster, and human papillomavirus disease. Collectively, the prevalence of IFN-I neutralizing autoAbs in people with HIV, whether ART-treated or ART-naive, did not significantly differ from that in the general population. Whereas hepatitis C and IFN therapy may contribute to the development of autoAbs to IFN-I, these autoAbs in turn seem to predispose to mucocutaneous herpesvirus infections and HPV-related neoplasia.

Acyclovir and valacyclovir have been widely used for the treatment of herpes virus infections, including herpes zoster, with generally favorable outcomes. However, in patients with chronic kidney disease, particularly those undergoing peritoneal dialysis or hemodialysis treatment, neurotoxicity can be a significant complication as renal excretion is the primary elimination pathway. Here, we report three cases of automated peritoneal dialysis patients treated for herpes zoster who developed neurotoxicity following acyclovir or valacyclovir administration. Symptoms appeared 2 to 4 days after treatment initiation. They included mental confusion, psychomotor agitation, dizziness, dysgeusia, anosmia, blurred vision, gait instability, hallucinations, dysarthria, paresis, involuntary lower-limb movements, ataxia, and anorexia. Neurological symptoms gradually resolved after drug discontinuation, alongside complete regression of zoster lesions. Despite decades of clinical experience and numerous reports, acyclovir and valacyclovir-induced neurotoxicity continue to occur in patients with severe renal impairment. This report underscores the importance of dose adjustment and close monitoring, emphasizing that neurotoxicity, although rare, can occur even at apparently safe doses in patients undergoing peritoneal dialysis.

Mastitis caused by Staphylococcus aureus (S. aureus) poses a significant challenge in dairy farming because of its impact on animal health and milk production. Understanding the regulatory role of N6-Methyladenosine (m6A) modification in this disease remains crucial. Here, we used direct RNA sequencing (DRS) to explore transcriptomic changes in bovine mammary epithelial cells (BMECs) exposed to S. aureus (SA) compared to untreated controls (MEC). We identified 178 differentially expressed isoforms (DEIs) enriched in pathways such as the TNF signaling pathway, Kaposi's sarcoma-associated herpesvirus infection, IL-17 signaling pathway, NF-kappa B signaling pathway, and rheumatoid arthritis. Most DEIs in these pathways exhibited m6A modifications, with 18 DEIs implicated in inflammation. Functional assays revealed that S. aureus increased the m6A levels of CCL20 mRNA, enhancing its stability via an m6A-YTHDF2-dependent mechanism, which led to elevated CCL20 expression. Silencing YTHDF2 increased IL-6 and TNF-α levels, whereas IL-10 expression decreased. Western blotting confirmed the role of YTHDF2 by showing elevated PI3K, Akt, and NF-κB levels in SA-treated cells following YTHDF2 silencing. These findings suggest that m6A-mediated regulation of CCL20 in S. aureus-induced BMECs operates via the PI3K/Akt/NF-κB pathway. These findings underscore the significance of m6A-mediated CCL20 regulation in mastitis pathogenesis and suggest potential therapeutic strategies for managing this economically significant disease in dairy farming.

Nuclear mechanics is remodeled not only by extracellular forces but also by internal modifications, such as those induced by viral infections. During herpes simplex virus type 1 infection, the nuclear structures undergo drastic reorganization, but little is known about how nuclear mechanobiology changes as a result. We show that the nucleus softens dramatically during the infection. To understand the phenomenon, we used advanced microscopy and computational modeling. We discovered that the enlarged viral replication compartment had a low biomolecular density, partially explaining the observed nuclear softening. The mobility of the nuclear lamina decreased, which suggests increased rigidity and an inability to induce softening. However, computational modeling supported by experimental data showed that reduced outward forces, such as cytoskeletal pull and intranuclear osmotic pressure acting both on and within the nucleus, can explain the decreased nuclear stiffness. Our findings reveal that during infection, the nucleus is subject to changes in multiple mechanical forces, leading to decreased nuclear stiffness.

Natural killer (NK) cells are central to antiviral immunity through a balance of activating and inhibitory receptors, including killer immunoglobulin-like receptors (KIRs). We have previously observed that an increased frequency of the inhibitory receptor KIR2DL2 and its ligand HLA-C1 is associated with heightened susceptibility to human herpesvirus (HHV) infection, supporting a role for KIR-mediated NK cell regulation in host-virus interactions. We investigated whether the co-infection of SARS-CoV-2 and human herpesvirus 6 (HHV-6) might be connected to the expression of KIR2DL2/HLA-C1. We analyzed 110 SARS-CoV-2-positive subjects and 109 SARS-CoV-2-negative subjects for the KIR2DL2 and HLA-C1 genotype and for HHV-6A/B reactivation in plasma samples. SARS-CoV-2-positive subjects showed a significantly higher frequency of the KIR2DL2/HLA-C1 haplotype and increased reactivation of HHV-6A. Among deceased and comorbid patients, the co-occurrence of the KIR2DL2/HLA-C1 haplotype and HHV-6A DNAemia was more frequent, particularly in those with cardiovascular disorders. These findings suggest that the KIR2DL2/HLA-C1 haplotype might promote NK cell inhibition, facilitating HHV-6A persistence and contributing to immune dysregulation during SARS-CoV-2 infection. The combined presence of KIR2DL2/HLA-C1 and HHV-6A may, therefore, represent a molecular signature of COVID-19 outcomes.

Background and Objectives: Kidney transplant recipients (KTRs) face increased susceptibility to persistent viral infections due to prolonged immunosuppression. While high-risk human papillomavirus (HR-HPV) infection is known to be more prevalent in this population, little is known about the co-occurrence of HPV with human herpesviruses (HHVs) infection in the female genital tract. This study aimed to investigate the presence, dynamics, and potential interactions between HR-HPV and HHVs infections-including HSV-1, HSV-2, EBV, CMV, HHV-6, and HHV-7-in female KTRs during the first year after transplantation. Materials and Methods: A total of 39 female KTRs and 79 age-matched healthy controls were enrolled in the study. Cervicovaginal swabs from recipients were obtained at three time points: two weeks, six months, and one year post-transplantation. HPV DNA was screened using PCR, followed by high-risk HPV genotyping and quantitative viral load assessment using two commercial PCR kits. HHVs were detected using a multiplex PCR assay. Results: HPV DNA was detected in 98% of the KTRs at least once during follow-up, which was significantly greater than in the controls (38%). HR-HPV was identified in 46% of the recipients over the study period, with the highest viral load at one year post-transplantation. HHVs were detected in 72% of the KTRs but not in 43% of the controls (p < 0.01), with EBV and CMV being the most common. Coinfection with HR-HPV and HHVs occurred in 46% of the recipients but not in the controls. Samples containing both EBV and CMV had significantly higher HR-HPV viral loads than samples with no HHVs or with single/other HHV combinations (p < 0.01). All cervical intraepithelial neoplasia patients were found to have combined HPV and HHV infection. Conclusions: Female KTRs present a high burden of both HR-HPV and herpesviruses infections, with increased HPV viral loads. These findings suggest a potential synergistic interaction between HR-HPV and herpesviruses in the immunosuppressed setting.

The article is devoted to one of the urgent problems of modern pediatrics - herpesvirus infections, which are widespread and can affect almost all organs and systems in children of any age. Practical recommendations are given on the diagnosis, treatment and prevention of this pathology in relation to nursing outpatient and hospital practice. The article presents the features of clinical manifestations of the most common forms of herpesvirus infections: cytomegalovirus infection, infectious mononucleosis, chickenpox and sudden exanthema. The role of herpesvirus infections caused by the herpes simplex virus, Epstein-Barr virus, cytomegalovirus and human herpes virus type 6 in children with recurrent upper respiratory tract diseases is emphasized. An assessment of laboratory and immunological studies in relation to herpes infections and their mixed combinations is given. The article presents modern possibilities of complex therapy of children with various forms of herpes infections, taking into account the use of both specific and symptomatic drugs, strengthening the immune system.

Chronic atrophic gastritis (CAG) is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions. Anwei decoction (AWD), a traditional Chinese medicine formula, has been shown to significantly improve clinical symptoms in patients with CAG, as demonstrated by a multicenter cohort study (overall effective rate: 82.5%, P < 0.01). However, the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance. To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective. In this study, N-methyl-N'-nitro-N-nitrosoguanidine was used to establish a CAG rat model. Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay. Moreover, gastric mucosal tissues were analyzed by quantitative real-time polymerase chain reaction to measure messenger RNA (mRNA) levels of the NLRP3 inflammasome. Western blotting was used to detect the protein expression of NLRP3, caspase-1, and interleukin (IL)-1β. To elucidate the regulatory mechanisms underlying AWD treatment, structural alterations of the gut microbiota (GM) and associated metabolites were analyzed using integrated high-throughput sequencing (16S rRNA) and liquid chromatography-mass spectrometry based untargeted metabolomics. This comprehensive approach systematically clarified AWD's multi-target therapeutic mechanisms against CAG. AWD notably reduced serum levels of pro-inflammatory cytokines, such as IL-1β, IL-18, tumor necrosis factor-α, and lipopolysaccharide, demonstrating significant statistical differences (all P < 0.01). Additionally, AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue (P < 0.01) and concurrently decreased the protein abundance of NLRP3, IL-1β, and caspase-1 (all P < 0.01), thereby suppressing inflammasome signaling activation. GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria. Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function. Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways, including the Kaposi's sarcoma-associated herpesvirus infection pathway, autophagy processes, and glycosylphosphatidylinositol-anchor biosynthesis. AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms. On one hand, AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation. On the other hand, AWD remodels intestinal microbiota-metabolite homeostasis, enhances intestinal barrier function, and regulates mucosal immune responses.

Great Horned Owls (Bubo virginianus; GHOW) are a true owl species (family Strigidae) widely distributed across the Americas. In GHOWs, herpesviral disease is best known from fatal infections with columbid alphaherpesvirus 1, which is endemic in rock pigeons (Columba livia). Recently, two novel alphaherpesviruses, strigid alphaherpesvirus 1 (StrAHV1) and strigid alphaherpesvirus 2 (StrAHV2), have been identified in GHOWs displaying ocular lesions and upper respiratory signs, respectively. To date, these are the only potentially endemic herpesviruses described in this species. This study aimed to develop and validate quantitative PCR (qPCR) assays for rapid detection of StrAHV1 and StrAHV2. Two singleplex probe-hybridization qPCR assays were developed for each virus, StrAHV1 and StrAHV2. Each primer-probe combination was cross-validated against the other. Whole blood and individual conjunctival, choanal, and cloacal swabs were obtained from 39 GHOWs hospitalized at three institutions in California, Colorado, and Florida in the USA and were run in duplicate for each assay. The highest number of copies of StrAHV1 detected and the greatest percentage of positive samples were from the choana (assay 1A: 15 of 35 [43%] positive, mean 194,030 copies, median 0 copies, range 0-3,411,469 copies; assay 1B: 16 of 35 [46%] positive, mean 197,622 copies, median 0 copies, range 0-3,554,915 copies). Conjunctiva had the next highest number of copies detected and positivity rate, followed by cloaca, with the number of copies detected and positivity rate both lowest in blood samples. A Kruskal-Wallis test using the choana results from the StrAHV1 assay 1A comparing the results from the three states found no significant differences (P=0.3443). No animals were positive for StrAHV2, suggesting that it may not be an endemic pathogen in GHOW. The qPCR assays developed can be used to further evaluate the epidemiology of StrAHV1 and StrAHV2 along with their clinical significance in GHOW.

Chronic hand eczema (CHE) is a distressing and pervasive dermatologic condition, and effective treatment can be challenging. The novel IL-4/13 inhibitor dupilumab has shown clinical efficacy for atopic dermatitis (AD) and is being studied for CHE.PubMed database was searched for terms dupilumab and chronic hand eczema/dermatitis, including CHE subtypes (dyshidrotic, hyperkeratotic, allergic, contact, atopic, occupational, vesicular). Twenty-two study publications met inclusion and exclusion criteria for evaluation.Two multicenter prospective studies, one randomized controlled trial, two prospective observational studies, one retrospective study, nine case series, and seven case reports were included in the analysis with 374 total patients. Any partial response or complete resolution of CHE occurred in 80.3% of patients treated with dupilumab within 4-16 weeks of treatment. The patient response tended to increase throughout the duration of these studies for a significant percentage of patients, and for many it lasted beyond the study duration. Significant improvement in hand eczema severity scores and quality-of-life scores were noted. Efficacy was reported in over half of the cases of hyperkeratotic hand eczema; however, efficacy was decreased compared with relatively high consistent efficacy in other CHE subtypes such as dyshidrotic, vesicular, atopic, and contact CHE. Patients with current or previous AD had increased improvement scores compared to those without. The most common adverse effects were conjunctivitis (9.9%), herpes viral infection (1.4%), and facial erythema/dermatitis (1.3%).Dupilumab shows therapeutic efficacy in treating CHE. Further randomized controlled studies of dupilumab use in CHE subtypes are needed.

Abstract Background JAK inhibitors and biologics are increasingly used to treat inflammatory bowel diseases (IBD). Serious infections are among the most important adverse events. Randomized trials are underpowered to detect relatively rare outcomes. We aimed to compare the risk of serious infections across IBD therapies in real-world practice. Methods We conducted a nationwide cohort study using French health data system (SNDS). All IBD patients aged aged more than 15 years, who intiated vedolizumab, ustekinumab, JAK inhibitors, anti-TNF, or aminosalicylates between 2014 and June 2024, were included. Patients with primary immunodeficiency, HIV, or organ transplantation were excluded. Follow-up ended at serious infection (hospitalization), treatment discontinuation, switch, or December 2024. Propensity score weighting accounted for indication bias, and weighted Cox models were adjusted for time-dependent corticosteroid and thiopurine/methotrexate use. Results We identified 309,025 treatment initiations in 219,229 patients (median age 41 years [IQR 29–55], 52% women, 45% Crohn’s disease). Over a median follow-up of 1.0 year (IQR 0.5–2.6), 15,081 serious infections occurred (incidence rate [IR] 26.1/1000 patient-years; 95%CI, 25.7–26.5). IRs were 21.9 (95%CI: 21.3-22.5) for aminosalicylates, 26.6 (95%CI: 25.2-27.9) for ustekinumab, 27.8 (95%CI: 27.1-28.4) for anti-TNF, 33.0 (95%CI: 31.4-34.6) for vedolizumab, and 38.9 (95%CI: 34.3-43.5) for JAK inhibitors. Compared with aminosalicylates, adjusted hazard ratios (aHR) for serious infection were 1.05 (95% CI, 0.98–1.11) for ustekinumab, 1.29 (95% CI, 1.42–1.54) for anti-TNF, 1.38 (95% CI, 1.30–1.46) for vedolizumab, and 1.63 (95% CI, 1.45–1.84) for JAK inhibitors. Patterns were consistent across Crohn’s disease and ulcerative colitis. Particular associations were seen between anti-TNF and vedolizumab and skin, upper respiratory, and neurologic infections; JAK inhibitors were associated with herpesvirus infections; anti-TNF were associated with mycobacterial infections. Concomitant corticosteroids and thiopurine/methotrexate further increased infection risk (aHR 2.06 [95% CI, 1.98–2.14] and 1.11 [95% CI, 1.06–1.16], respectively). Conclusion In this nationwide study, JAK inhibitors carried the highest risk of serious infection, ustekinumab the lowest, and anti-TNF and vedolizumab an intermediate risk. These findings may guide therapeutic choices in IBD patients at high risk of infection. Conflict of interest: Bertrand, Anaïs: No conflict of interest Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Martin, Antoine: Personnel fees : Abbvie, Janssen Carbonnel, Franck: Grant: Alpha Wassermann, Nestlé, Mayoly Spindler Personal Fees: Abbvie, Arena, Biogen, Celltrion, Enterome, Ferring, Janssen, MaaT Pharma, Nestlé, Nordic Pharma, Pierre Fabre, Pharmacosmos, Roche, Takeda, Tillotts, Viatris Meyer, Antoine: No conflict of interest

Autism spectrum disorder (ASD) is a neurodevelopmental condition of the central nervous system (CNS) that presents with severe communication problems of unknown cause. Few studies have explored the role of some herpesviridae members as potential etiological factors of ASD and phosphatase and tensin homolog (PTEN), a critical regulator of immune function, cellular growth, and neurodevelopment. This study aimed to assess the seropositivity of Herpes simplex virus-I (HSVI), Herpes simplex virus-II (HSVII), Epstein–Barr virus (EBV), and cytomegalovirus (CMV) in children with ASD. Also, the goal of the study was to explore whether viral exposure contributes to ASD through PTEN downregulation and neuroimmune disruption. Serum PTEN levels and their correlation with viral infections were examined. The seropositivity rate to HSV-I, HSV-II, EBV, CMV, and PTEN serum levels was estimated in 100 blood samples from autistic children (65 males and 35 females). The age range was 3 to 14 years, with a mean age of 5.87 ± 2.544 years. An enzyme-linked immunosorbent assay (ELISA) was used. Interestingly, the results demonstrated statistically significant negative correlations across all viral markers, indicating that higher levels of viral infection are associated with lower PTEN expression. Specifically, HSV I showed the strongest negative correlation with PTEN levels (r = –0.48, p &lt; 0.001), followed by EBV (r = –0.45, p &lt; 0.001), HSV II (r = –0.41, p = 0.001), and CMV (r = –0.39, p = 0.002). These findings suggest a consistent pattern in which increased viral load may be contributing to the downregulation of PTEN. This relationship reinforces the hypothesis that viral infections may contribute to reducing PTEN signaling, which could play a role in the pathophysiology of ASD through immune dysregulation or altered neurodevelopmental pathways.