Varicella-zoster virus (VZV) causes varicella in children, establishes lifelong latency and reactivates to cause herpes zoster later in life. Implementation of routine varicella vaccination in Japan since 2014 has reduced varicella cases, however, breakthrough varicella still occurs. This study aimed to clarify the current distribution of VZV clade among pediatric varicella patients and adults with VZV-associated central nervous system (CNS) infections in Japan. Skin swabs were collected from varicella patients (< 15 years) in Aichi Prefecture (September 2015-August 2017). Cerebrospinal fluid (CSF) samples were obtained from adult patients (> 15 years) with VZV-associated CNS infections (November 2014-June 2023). VZV DNA was detected by PCR, and its clade was determined by sequencing open reading frame (ORF) 22 and ORF37 regions. Wild-type and Oka vaccine strains were distinguished by loop-mediated isothermal amplification (LAMP) method. Of 124 pediatric swab samples and 62 adult CSF samples 94.4% belonged to clade 2 and 4.8% clade 1. No clade 1 samples were detected in CSF samples. No vaccine strain was detected. Clinical characteristics did not differ significantly among clades. Clade 2 VZV predominates in both pediatric varicella and adult VZV-related CNS infections in Japan with sporadic clade 1 varicella cases.

Oropouche fever is an arboviral disease caused by the Oropouche virus (OROV; Peribunyaviridae family), first identified in Brazil in 1960. This study aims to describe the epidemiological profile and spatio-temporal dispersion of Oropouche fever cases across Brazil in 2024. The variables analyzed were sex, age, transmission area, macroregion, and federative unit. A simple descriptive analysis (absolute frequencies and proportions) was performed. Data were extracted from the Oropouche Fever Epidemiological Panel and the Brazilian Institute of Geography and Statistics (IBGE). The analysis revealed 13,786 reported cases (6.80/100,000 inhabitants), with a predominance of males (52.6%; n = 7247). The North region presented the highest incidence (41.60%; n = 5732; 33.03/100,000 inhabitants). Incidence peaks during early (weeks 5-6) and late 2024 (week 52) were identified, with heterogeneous regional spread reflecting a possible outbreak progression from the North to Northeast and subsequently Southeast. Espírito Santo state recorded the highest national incidence (151.60/100,000 inhabitants; 42.20% of cases; n = 5812). The expansion of OROV into non-endemic regions highlights an emerging public health threat. Urgent, systematic measures are required to strengthen Brazil's health surveillance system, ensuring timely and effective responses to mitigate further geographic spread.

Despite effective viral suppression, a subpopulation of people living with HIV (PLWH) receiving combination antiretroviral therapy (ART) experience a suboptimal immunological response, failing to restore CD4 T-cell counts to levels deemed indicative of good immune recovery. Innate immune cell dysregulation, particularly in mucosal-associated invariant T (MAIT) and natural killer (NK) cells, is increasingly recognized as a key contributor to immune reconstitution. However, the dynamic changes, interactive crosstalk, and potential roles of these immune cells in immune reconstitution remain poorly understood. A total of 89 participants were enrolled, including 29 healthy controls and 60 HIV-infected individuals, who were classified as immune responders (IRs, CD4 ≥ 500 cells/µL; n = 34) and suboptimal immunological responders (SIRs, CD4 < 500 cells/µL; n = 26) on the basis of immune recovery status. Longitudinal flow cytometric analysis was performed to assess the phenotypic changes in MAIT and NK cell subsets in peripheral blood mononuclear cells (PBMCs) before treatment (T0) and after 4 years of ART (T4). Correlation analysis was conducted to explore their associations with CD4 T-cell recovery. After 4 years of ART, both IRs and SIRs exhibited persistent depletion of total MAIT and invariant natural killer T (iNKT) cells, whereas pretreatment-diminished CD56 and CD56 NK cell subsets increased significantly. MAIT cells also underwent phenotypic remodeling in both groups, with decreased CD4CD8 and increased CD4CD8 subsets. Notably, these cell subset proportions and quantitative changes correlated significantly with CD4 T-cell counts in IRs but not SIRs. In IRs, CD4 T-cell recovery positively correlated with baseline CD4CD8 MAIT and CD56 NK cell numbers, but negatively with baseline CD4CD8 MAIT cell numbers. Correlation networks revealed distinct MAIT-NK interactions across ART stages. LASSO models integrating MAIT and NK subsets achieved high predictive accuracy, highlighting the dynamic role of CD4CD8 MAIT cells in immune reconstitution. Our study highlights the dynamic correlations between and within MAIT and NK cell subset proportions in PLWH, revealing that phenotypic remodeling rather than absolute cell counts plays a key role in immune reconstitution. CD4CD8 MAIT cells show time-dependent predictive shifts, reflecting functional adaptation. These findings identify MAIT and NK subset dynamics as potential biomarkers and therapeutic targets for enhancing immune recovery of PLWH during ART.

Ocular adverse events following COVID-19 vaccination are well described; however, systematic analyses of non-COVID antiviral vaccines remain limited. This review aimed to evaluate ocular complications associated with non-COVID antiviral immunizations, including influenza, varicella-zoster (VZV), human papillomavirus (HPV), and hepatitis B (HBV) vaccines. A systematic search (PROSPERO CRD4202450873) identified 122 patients (184 eyes) from 8,487 publications, including case reports, case series, and observational studies. Uveitis was the most common (92/184 eyes; 50.0%, 95% CI 42.8%-57.2%), frequently following influenza vaccination (35/122; 28.7%, 95% CI 20.7%-36.7%). Most patients (95/122; 77.9%, 95% CI 70.5%-85.3%) required systemic corticosteroids, reflecting predominant inflammation. Ocular symptoms occurred within 30 days in 84.4% (103/122)of cases, with peak onset at 7-30 days (62/122; 50.8%, 95% CI 42.0%-59.6%). Despite appropriate treatment, 18 patients (20.0%, 95% CI 13.0%-29.4%) experienced persistent inflammation or required therapy beyond 1 month, categorized as "long-vax", defined as ocular symptoms persisting for ≥ 4 weeks after vaccination. Although rare, antiviral vaccine-associated ocular complications may persist, posing a risk of long-term visual morbidity and emphasizing the importance of clinician awareness, postvaccination surveillance, and counseling for patients receiving repeated or combined vaccine exposures.

Severe fever with thrombocytopenia syndrome virus (SFTSV) infection is associated with poor clinical outcomes and defective humoral immunity yet the immunometabolic mechanisms underlying B cell dysfunction remain incompletely defined. Through integrated single-cell RNA sequencing and B cell receptor (BCR) repertoire profiling of peripheral B cells from SFTS patients, we dissected the molecular signatures between survivors and fatal cases. Functional validation and metabolic flux analysis were further performed. Seven transcriptionally distinct B cell subsets were identified. Fatal cases exhibited a marked expansion of CXCR3+Ki-67+CXCR5- extrafollicular plasmablasts, coupled with depletion of naïve and memory B cells. These plasmablasts exhibited hyperactivation of interferon-response genes (IFI27, ISG15), upregulation of inflammatory mediators (S100A8/A9), and contraction of BCR diversity, with skewed usage of λ-light chains. Pseudotime trajectory analysis and metabolic scoring revealed progressive upregulation of oxidative phosphorylation, glycolysis and endoplasmic reticulum stress during terminal differentiation. In fatal cases, B cells exhibited suppressed antigen presentation capacity and impaired immunoglobulin gene expression, alongside heightened oxidative stress and elevated CD39 levels. Furthermore, analysis of SFTSV-infected versus uninfected B cells revealed that infected plasmablasts displayed enhanced inflammatory and migratory features, including upregulated CXCR3 and CCR10 expression, suggesting direct viral modulation of B cell function and trafficking. Our study reveals that dysfunctional, metabolically reprogrammed plasmablasts underlie humoral immune failure in fatal SFTS. These findings provide mechanistic insight into B cell-mediated immunopathogenesis and highlight potential targets for prognostic evaluation and immunomodulatory intervention.

To identify the cell types that are infected with KSHV and the immune interactions in Kaposi sarcoma (KS) lesions, we performed spatial transcriptomics with seven KS skin tumors. We used a single-cell RNA-sequencing reference data set from healthy skin donors with a method to conduct spatially informed cell-type deconvolution for spatial transcriptomics. This allowed us to predict the relative amounts of each cell type within the patient sample sections. We included custom probes for five KSHV genes that allowed us to measure human and KSHV expression patterns at the same time. We then compared the spatial gene expression data of KS skin samples with six normal skin samples and found higher expression of marker genes corresponding to macrophages/dendritic cells, lymphatic endothelial cells, and vascular endothelial cells in the KS skin lesions when compared to normal skin samples. Our spatial transcriptomic results from thousands of spots across multiple KS tumors indicated a correlation between high levels of STC1 and decreased expression of macrophage markers. Together, these analyses offer potential mechanisms by which KSHV infection may remodel skin tissue, inhibit immune responses against KSHV infection, and confer resistance to anticancer therapies.

Cytomegalovirus (CMV) infection remains a major contributor to CMV-related and hematologic adverse outcomes in hematopoietic stem cell transplantation (HSCT) recipients. While letermovir has improved CMV prophylaxis strategies in this population, the clinical implications of low-grade CMV DNAemia during letermovir prophylaxis remain uncertain. We retrospectively analyzed 255 HSCT recipients who received letermovir at a tertiary hospital in Korea. Patients were stratified into three groups based on the highest CMV DNAemia levels observed during letermovir prophylaxis: no DNAemia (n = 72), low-grade DNAemia (< 1000 IU/mL; n = 171), and high-grade DNAemia (≥ 1000 IU/mL; n = 12). The association between low-grade CMV DNAemia and clinical outcomes was assessed using a multivariate Cox proportional hazards model. Most low-grade DNAemia cases were transient and resolved without antiviral therapy. Compared to no DNAemia, low-grade CMV DNAemia was not associated with an increased risk of clinically significant CMV infection by Day 100 (p = 0.262) or Day 365 (p = 0.399). No significant associations were observed with engraftment failure (p = 0.098), disease relapse (p = 0.165), or all-cause mortality (p = 0.537). Our findings suggest that close monitoring may be sufficient for low-grade DNAemia under letermovir prophylaxis.

Hepatitis B virus (HBV) infection is a significant global public health concern. The virus exhibits broad tropism and can affect various organs and systems besides the liver. Among various HBV-related extrahepatic diseases, glomerulonephritis, represented by membranous nephropathy, is the most common type. HBV-associated membranous nephropathy (HBV-MN) typically manifests as nephrotic syndrome with an insidious onset. Notably, 30% of adult patients progress to renal failure, underscoring the urgency for early diagnosis and intervention. Current challenges encompass underdiagnosis risks in occult HBV-MN, lack of stratified guidance in treatment strategies, marked heterogeneity of immune complex deposition patterns in HBV-GN, and incompletely characterized pathogenic mechanisms. This review synthesizes current understanding of HBV-MN, covering clinical manifestations, therapeutic interventions, and mechanistic insights into the signaling pathways involved in its pathogenesis.

This study aimed to investigate the impact of preconception maternal inactivated COVID-19 vaccination on fetal metabolic recovery following maternal SARS-CoV-2 infection during pregnancy. Umbilical cord blood samples were collected from neonates born to mothers with SARS-CoV-2 infection during pregnancy. Mothers were stratified into two groups: those fully vaccinated (inactivated COVID-19 vaccines) before conception (n = 81) and unvaccinated (n = 56). Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was employed for metabolomic profiling. The vaccinated group exhibited markedly reduced amino acid/purine metabolism dysregulation and oxidative stress compared to unvaccinated counterparts. Crucially, within the critical IRT window of 5-6 months, vaccination effectively suppressed mTOR signaling-driven pathological metabolic remodeling. In contrast, the unvaccinated group demonstrated sustained metabolic disturbances (> 6 months from infection). In conclusion, preconception maternal inactivated COVID-19 vaccination reprograms fetal metabolism and accelerates intrauterine recovery from maternal SARS-CoV-2 infection, which may confer a beneficial impact on early-life growth. It prevents the establishment of a detrimental "metabolic memory" effect posing potential developmental risks. These findings reveal a novel non-immune, metabolome-mediated protective mechanism of maternal vaccination, which thus supports COVID-19 vaccination for women of childbearing age.

The devastating clinical, psychological, and economic impact of the COVID-19 pandemic, caused by global spread of the second Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has engendered a massive response from the scientific community to rapidly understand the biology of SARS-CoV-2 and to develop interventions to prevent infection or progression to life-threatening disease. Angiotensin converting enzyme-2 (ACE2) and its interaction with the SARS-CoV-2 Spike glycoprotein, which mediates fusion of the virion envelope with the target cell membrane, have emerged as a major pharmacological target, as disruption of the Spike-ACE2 interaction prevents cells from becoming infected and hence from producing viral progeny. Moreover, the dysregulation of ACE2 that occurs in the context of SARS-CoV-2 infection may have broader implications for COVID-19 pathogenesis. Here we summarize the role of ACE2 as a physiologic regulator of human health, as a facilitator of SARS-CoV-2 infection, as a factor in COVID-19 disease, and as a target for pharmacological interventions.

Human norovirus has been identified as a significant causative agent of acute gastroenteritis on a global scale. We investigated the epidemiological of norovirus infections in children with acute gastroenteritis in Shanghai between January 2022 and December 2024. The overall prevalence of norovirus was 13.22% (281/2126), with annual rates of 3.77% (20/531) in 2022, 18.30% (149/814) in 2023, and 14.34% (112/781) in 2024. The 281 norovirus strains were classified into the GI group (0.71%, 2/281) and GII group (99.29%, 279/281). Phylogenetic analysis revealed that 90.39% (254/281) of HuNoV strains were successfully genotyped for both VP1 and RdRp genes, with 15 distinct genotype combinations. The most prevalent strain was GII.4 Sydney[P16] (52.36%, 133/254), followed by GII.17[P17] (21.26%, 54/254) and GII.3[P12] (11.42%, 29/254). Of note, GII.4 Sydney[P16] was observed in both 2022 (56.25%, 9/16) and 2023 (74.10%, 103/139), while GII.17[P17] emerged as the predominant genotype in 2024 (43.43%, 43/99). Furthermore, most of the GII.17[P17] strains identified in 2024 clustered with GII.17[P17] strains identified in the United States in 2025. These findings provide new insights into the genetic diversity of HuNoV and indicate a resurgence of a new GII.17[P17], which has become a leading cause of sporadic AGE in children in Shanghai.

Herpes simplex virus type 1 (HSV-1) encodes the serine/threonine kinase US3, a central regulator of host-virus interactions that promotes viral replication, latency, and reactivation. Despite limited sequence homology to cellular kinases such as Akt or PKA, US3 phosphorylates diverse substrates to manipulate multiple pathways. This review summarizes current knowledge of US3 functions across several major areas, including suppression of innate immune responses through modulation of NF-κB, ERK/MAPK, TBK1/IRF3, RIG-I; promotion of cell survival via phosphorylation of canonical Akt substrates such as TSC2, FOXO1/3, and BAD; and facilitation of nuclear egress through modification of lamin A/C, emerin, and the nuclear egress complex proteins UL31 and UL34. By comparing US3's strategies with those of cellular kinases and other viral effectors, this review highlights convergent mechanisms of host manipulation. A comprehensive understanding of US3's multifunctional activities advances insight into HSV-1 pathogenesis and underscores its potential as a target for novel antiviral therapies.

Persistent exposure to high-risk human papillomavirus (HR-HPV) is a major contributing factor to cervical cancer. HPV-52, -58, and -16 are the top three prevalent HR-HPV types in Jingzhou. In this study, samples monoinfected with HPV-52 (n = 96), -58 (n = 98), and -16 (n = 100) were collected between August 2022 and October 2023. The L1 genes were sequenced and analyzed to characterize genetic diversity. After constructing phylogenetic trees, secondary structure analysis and B-cell epitope prediction were conducted. The HPV-52 L1 sequences contained 35 single-nucleotide variations in total. Six of them were recently figured out, while 29 were synonymous and 6 were nonsynonymous. Of the 44 single-nucleotide polymorphisms (SNPs) found for HPV-58 L1, 10 were newly discovered. For HPV‑16 L1, 29 SNPs, one deletion and one insertion were identified, with four newly detected variants. Phylogenetic analysis revealed that all HPV-52 L1 sequences were clustered within sublineage B2, whereas 58.33% of the variations in HPV-58 L1 sequences were distributed in sublineage A1, and the majority of the variations in HPV-16 L1 sequences were located in sublineage A4 (55/70). No positively selected site was detected in the HPV-52, -58, and -16 L1 sequences. The predicted B-cell epitopes may be impacted by the nonconservative substitutions K200R and E468D in HPV-52 L1; L150F, I325M, K523T, K523N, K524R, and K524Q in HPV-58 L1; and N16D in HPV-16 L1. This study establishes a foundational data set on L1 genetic diversity of HPV-52, -58, and -16 prevalent in Central China and offers valuable insights for the development of region-specific prophylactic vaccines.

Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus that causes severe febrile and hemorrhagic illness in humans. In September 2025, an outbreak in northern Senegal led to 119 confirmed infections and 15 deaths as of October 7, 2025. We performed rapid genomic sequencing to characterize the virus responsible for this epidemic. RNA from RT-qPCR-confirmed samples was sequenced using the Twist Comprehensive Viral Research Panel on an Illumina iSeq 100 platform. Consensus genomes were analyzed with and compared with all complete RVFV genomes in GenBank. Nine genomes were recovered, including five complete tripartite sequences. All clustered within lineage H, sharing > 99% nucleotide identity with Senegalese isolates from 2020 to 2022. Alongside two conservative mutations (R137K and K1111R in S and M segments, respectively), a single nonconservative D11N substitution in the L polymerase may affect replication efficiency, while Gn and Gc epitopes remained conserved. Phylogenetic analyses confirmed strong genetic continuity with earlier West African isolates, indicating local persistence rather than reintroduction. Lineage H persistence in Senegal, combined with polymerase substitutions under purifying selection, suggests subtle viral adaptation that may affect replication. Conserved glycoprotein epitopes indicate maintained vaccine relevance. Sustained genomic surveillance integrated with clinical and ecological monitoring remains essential to anticipate viral evolution and guide Rift Valley fever control.

HCoV-OC43 genomes and their evolution are scarcely studied worldwide and in France, with only 361 genomes available as of October 2023. Here, an in-house PCR amplification system was implemented to obtain retrospectively by next-generation sequencing, then analyze HCoV-OC43 genomes for infections diagnosed with this virus in southern France between February 2017 and October 2022. Multiplex PCR amplification using a set of in-house primers designed with the Gemi software was carried out on residuals of HCoV-OC43 RNA-positive nasopharyngeal samples, before next-generation sequencing (NGS) using Illumina technology on a NovaSeq. 6000 instrument. HCoV-OC43 genome assembly, bioinformatic analyses, and phylogeny reconstruction were then carried out using CLC Genomics, Mafft, BioEdit, Nextstrain, Nextclade, MEGA, iTOL, RDP4, and HyPhy softwares. Spike structural predictions used AlphaFold and HyperChem. A total of 34 PCR primer pairs were designed for amplification, before NGS of amplicons generated from HCoV-OC43 genomes. A total of 185 genomes were obtained, 17, 79, and 89 belonging to Genotypes G, J, and K, respectively. These three genotypes circulated exclusively or co-circulated according to the year. A total of 303, 940, and 1300 amino acid substitutions were detected in genomes of genotypes G, J, and K, respectively, compared with reference genomes of the same genotype dating back to 2017-2018. Possible recombinations were detected for five HCoV-OC43 genomes and involved genomes classified in genotypes J or K. HCoV-OC43 genes encoding the hemagglutinin esterase, the spike, and the Nsp14 protein harbored the greatest number of sites under positive selection. Signature amino acid mutations F467V and S507G in the spike protein of genotypes J and G, respectively, were predicted to decrease the binding of 43E6 neutralizing antibody. Overall, the present study more than doubled the set of HCoV-OC43 genomes available worldwide for the 2017-2022 period and contributed to the monitoring of the HCoV-OC43 evolutionary dynamics.

Chikungunya virus (CHIKV) infection poses a worldwide health risk and negatively impacts the well-being of those infected for an extended period. Understanding the characteristics of the circulating virus within the population and its virological, immunological, and molecular aspects is essential for developing effective control measures and improving disease management. The current study assessed 69 clinical CHIKV isolates obtained from acute serum samples collected from patients across India between 2016 and 2022. CHIKV was successfully isolated from 69 acute serum samples, and plaque size/morphology and the growth kinetics of the clinical isolates were analyzed. The findings indicated that there was a significant correlation between the plaque size of CHIKV isolates and the virus's growth kinetics, viral load, and immune response, all of which may affect disease outcomes. Specifically, larger plaque variants were associated with more severe symptoms and faster recovery from the disease, whereas smaller plaque variants were linked to persistent arthralgia and a greater likelihood of chronic disease. These findings highlight the potential of using plaque size as a predictive factor for disease progression and emphasize the importance of considering plaque morphology in CHIKV disease outcome studies.

Hepatitis is a systemic disease marked by neuroimmune dysregulation beyond hepatic inflammation. Using a systems biology approach, we conducted transcriptomic meta-analyses across in vitro models, liver tissues, and PBMCs from hepatitis virus-infected patients to identify neuroimmune signatures. We found a robust neuroimmunome signature, with neuroimmune-related genes showing consistent differential expression across datasets. Functional enrichment revealed disruptions in neurotransmission (including synaptic, glutamatergic, noradrenergic and neuregulin pathways) and immune signaling (such as cytokines, interleukin-1 response, T cell receptor, and trans-synaptic signaling). Linear discriminant analysis (LDA) demonstrated that neuroimmune genes can predict disease severity. Several of these genes were also altered in hepatocellular carcinoma (HCC) samples from The Cancer Genome Atlas Program (TCGA), implicating them in oncogenic transformation. Ligand-receptor analysis revealed dysregulated neuroimmune interactions in liver tissue, notably involving DBH-ADRA1A/B/D, ADRA2A/B/C, ADRB1/2/3, IL33-IL1RL1, and NRG1-ERBB4. Critically, we observed an inverse correlation between neuroimmune gene expression and inflammation markers in advanced HCC, suggesting that neuroimmune suppression may facilitate immune evasion. These findings highlight the neuroimmunome as a potential biomarker and therapeutic target in hepatitis and its complications, reinforcing the role of neuroimmune crosstalk in liver disease progression.