Natural killer (NK) cell antibody-dependent cellular cytotoxicity (ADCC) contributes to effective antiviral immunity, yet the relative contribution of NK cell-intrinsic factors and antibodies in mediating these responses remain poorly understood. Here, we combined functional ADCC assays with single-cell transcriptomics of peripheral NK cells from COVID-19 participants. Our analysis revealed distinct transcriptional programs between participants with different ADCC response levels: NK cells from participants with lower ADCC responses upregulated proliferation pathways, while those with high ADCC responses showed enhanced expression of interferon-stimulated genes and NKG2D. Blocking NKG2D significantly reduced NK cell ADCC degranulation and cytokine responses. Paradoxically, greater interferon-mediated NK cell activation was associated with reduced proficiency of participants' antibodies to mediate ADCC, suggesting a regulatory checkpoint mechanism. These findings enhance our understanding of the molecular determinants of ADCC responses and provide novel insights into leveraging these responses for more effective vaccination and therapeutic strategies.

Immune pathways are vital for insect vectors to combat viruses, yet arboviruses can evade this innate immunity, enabling persistent transmission. However, the mechanisms maintaining this immune homeostasis are still poorly understood. This study thus aimed to decipher how the immune deficiency (IMD) pathway contends with rice gall dwarf virus (RGDV), a highly detrimental rice reovirus transmitted by leafhopper Recilia dorsalis. Notably, RGDV infection activated the peptidoglycan recognition protein 1 (PGRP1) upstream of the IMD pathway, which transmits signals to initiate the downstream Relish-defensin1 cascade. Defensin1 is transcribed by the transcription factor Relish and serves as a broad-spectrum antiviral peptide of the IMD pathway. Defensin1 promotes E3 ubiquitin ligase FBXW7-mediated ubiquitination and degradation of viral tubular protein Pns11, inhibiting viral infection and transmission. However, the viral structural protein P8 hinders the nuclear translocation of Relish, thereby promoting the coexistence of arboviruses with their insect vectors. The IMD pathway-derived defensin1 mediates antiviral immunity in insect vectors. This study reveals a novel immune strategy in leafhoppers that confers resistance to rice viruses and elucidates an RGDV-mediated mechanism for suppressing innate immunity. © 2026 Society of Chemical Industry.

USP18 orchestrates malignant progression in nasopharyngeal carcinoma through UBR5-driven attenuation of p53 signaling.

Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is a rare pediatric epilepsy syndrome characterized by prolonged focal febrile seizures, postictal hemiparesis, and progressive unilateral brain injury, often followed by chronic epilepsy. We report a previously healthy 10-month-old girl who presented with a prolonged left-sided focal fever-associated seizure. She tested positive for SARS-CoV-2 but did not meet criteria for multisystem inflammatory syndrome in children. On admission, she had left-sided flaccid hemiparesis. Brain MRI showed mild diffusion restriction and marked hyperperfusion of the right hemispheric gray matter, most prominently in the frontal, temporo-occipital, and hippocampal regions. EEG showed high-amplitude slowing over the right hemisphere without epileptiform discharges. No further seizures occurred, and long-term antiseizure treatment was not required. At 9-month follow-up, the patient was seizure-free and developmentally age-appropriate, but the hemiparesis persisted. Serial MRI showed progressive right hemispheric cortical and subcortical atrophy and hippocampal sclerosis. Extensive diagnostic workup found no other structural, infectious, or metabolic cause. This case illustrates the classical biphasic course of HHE syndrome and highlights the diagnostic value of early MRI, EEG, and genetic testing. The patient carried a paternally inherited heterozygous IRF3 variant, a gene essential for innate antiviral immunity. Although causality cannot be established, the temporal association with SARS-CoV-2 infection and an IRF3 variant suggests a possible genetic predisposition to infection-triggered injury. Continued clinical vigilance and long-term follow-up are essential, as epilepsy develops in most children with HHE. Greater awareness of this syndrome may support earlier recognition and timely rehabilitation to optimize functional outcomes.

PmVago1 and PmVago4 from Penaeus monodon act as cytokine-like mediators of antiviral immune responses to white spot syndrome virus in penaeid shrimp.

Advances in TCDD-inducible poly(ADP-ribose) polymerase (TiPARP/PARP7) research: From molecular mechanisms to therapeutic applications.

Overcoming barriers in cancer therapy with oncolytic adenoviruses: Engineering strategies and clinical perspectives.

An involvement of ribonuclease L in Parkinson's disease via modulating the Th17/Treg balance by microRNA-7.

PRRSV interaction with the adaptive immune system of host: an update review.

Metabolic reprogramming is implicated in the differential response of the CAL-1 plasmacytoid dendritic cell line to autophagy inhibitors.

Functional characterization of grass carp (Ctenopharyngodon idella) jmjd8 gene in the anti-GCRV immune response.

The RNA sensor MDA5 contributes to the antiviral immune response in Crassostrea gigas by modulating the MAVS-mediated signaling pathway.

Natural killer (NK) cells are pivotal effectors in antiviral immunity, yet their tissue-specific roles during acute HIV infection remain poorly defined. Using an ex vivo human tonsillar tissue model, we profile NK cell responses to early HIV infection and uncover distinct subsets with specialized functions. We identify a previously uncharacterized memory-like NK population (CD16+/−CD69+CD49a+CD103+NKG2C+) associated with reduced viral burden and enriched in cytotoxic mediators (GNLY, PRF1, and GZMB), apoptotic ligands (FASLG and TRAIL), cytokine receptors (IL2RA, IL2RB, IL2RG, IL12RB2, and IL18R1) and trafficking molecules (CCL3–5, CCR7, and SELL). Although functionally capable of clearing HIV-infected CD4+ T cells in a tissue-mimetic environment, they show impaired cytotoxicity and transcriptional signs of exhaustion after infection. Conversely, HIV drives the reprogramming of immature CD16−CD69+ NK cells toward a more cytotoxic and migratory effector phenotype. These findings reveal dynamic NK cell adaptations in lymphoid tissue during early HIV infection and highlight tissue-resident NK cells as promising targets for immunotherapeutic intervention.

Tomato spotted wilt virus (TSWV) is one of the most important plants segmented negative-strand RNA viruses (NSVs). Plants employ the ubiquitin–proteasome system (UPS) and autophagy pathways to degrade viral effector proteins, forming a key antiviral defense layer. SnRK1 functions as a central energy sensor and plays pivotal roles in plant growth and development, as well as immune defense. However, whether SnRK1 modulates the infection of plant segmented NSVs and the underlying regulatory mechanisms remains elusive. In this study, we found that nonstructural protein NSs, a viral suppressor of RNA silencing (VSR) encoded by TSWV, specifically interacts with the catalytic α subunit of host SnRK1 (SnRK1α). NbSnRK1α promotes the degradation of NSs via the 26S proteasome pathway, independently of autophagy. Transient silencing of NbSnRK1α led to increased accumulation of the NSs protein. Furthermore, we found that NbSnRK1α significantly impairs the VSR activity of NSs by promoting its degradation, thereby restoring the host’s RNAi-mediated antiviral defense. Subsequent viral infection assays confirmed that NbSnRK1α inhibits TSWV replication, whereas silencing NbSnRK1α enhances the susceptibility of Nicotiana. benthamiana to TSWV infection and facilitates systemic viral spread and disease symptom development. Our study uncovers a new antiviral defense case by which NbSnRK1α enhances host antiviral immunity through targeting a segmented negative-strand RNA viral effector for 26S proteasomal degradation, broadening the understanding of the NbSnRK1’s role in broad-spectrum antiviral defense.

Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract disease in infants worldwide. Despite extensive study in animal models and humans, fundamental age-dependent differences in mucosal immunity continue to limit the development of durable protective strategies in early life. Compared to adults, infants mount weaker humoral responses to RSV, underscoring the urgent need for effective vaccines in this age group. Immunoglobulin A (IgA), the dominant antibody isotype at respiratory mucosal surfaces, plays a central role in limiting viral replication and disease severity during RSV infection. While IgA limits RSV severity in adults, infants fail to generate robust IgA responses. Impaired IgA responses in infancy reflect unique immune regulatory pathways that shape early-life antiviral immunity. Emerging evidence highlights a critical role for regulatory B cells (Bregs), particularly neonatal Bregs (nBregs), in suppressing antiviral responses, limiting class switch recombination, and contributing to severe RSV disease. This review summarizes current evidence on IgA regulation during RSV infection, with particular emphasis on age-specific B-cell responses and the emerging role of Bregs. Improved understanding of these mechanisms has direct implications for the rational design of vaccines and immunomodulatory strategies tailored to infants.

An OASL homologue involved in IFN-like antiviral signal by binding MDA5 in the Pacific oyster Crassostrea gigas.

Plant viruses cause substantial yield and quality losses worldwide, and their rapid evolution can erode deployed host resistance. This review synthesizes current knowledge of antiviral resistance and tolerance mechanisms, using barley yellow dwarf virus (BYDV) in cereals as an illustrative case study. We first summarize key layers of plant antiviral immunity, including pre-formed physical and chemical barriers, dominant and recessive resistance genes, RNA silencing, hormone-regulated defense signaling, and degradation pathways such as the ubiquitin-proteasome system and selective autophagy. We then discuss how these mechanisms are exploited in breeding and biotechnology, covering conventional introgression, marker-assisted selection, QTL mapping and pyramiding, induced variation (mutation breeding and TILLING/ecoTILLING), transgenic strategies (pathogen-derived resistance and plantibodies), RNA interference-based approaches, and CRISPR-enabled editing of susceptibility factors. Finally, we highlight emerging nano-enabled tools and propose integrated strategies that combine genetic resistance with surveillance and vector management to improve durability under climate change and ongoing viral diversification.

Lysosomes are emerging as important signaling hubs for antiviral defense, yet how they enable type I interferon (IFN-β) production is unclear. Here, we identify an evolutionarily repurposed lysosomal pathway, centered on the LAMTOR-Rag GTPase complex, that governs IFN-β production through dual transcriptional and post-transcriptional regulation. Genetic ablation of LAMTOR or Rag GTPases in macrophages abolishes IFN-β responses despite intact pattern recognition receptor (PRR) signaling, uncovering a lysosome-specific checkpoint essential for antiviral immunity. Mechanistically, Rag GTPase activity controls IRF expression to prime IFN transcription, while upon PRR stimulation, the tumor suppressor FLCN recruits p38 MAPK to lysosomes, where Rag-dependent p38 phosphorylation stabilizes Ifnb1 mRNA. Nutrient availability dynamically modulates Rag nucleotide states and thereby its activation, linking IFN production to metabolic capacity. Notably, this checkpoint operates independently of mTORC1, illustrating how an ancient nutrient-sensing module has been co-opted for immune regulation. Disruption of the LAMTOR-Rag-FLCN-p38 axis impairs IFN induction in vitro and antiviral responses in vivo, underscoring its physiological significance. Our findings support the role of the lysosome as a central signaling hub integrating metabolic and immune cues, suggesting future directions for potential therapeutic strategies against viral infections.

The movement of dendritic cells and T cells within secondary lymphoid organs is critical for the development of adaptive immune responses1,2. Central to this process is the fibroblastic reticular cell (FRC) network, which forms a highly organized conduit system that facilitates the movement of and interactions between dendritic cells and T cells3-6. Previous studies have partly characterized how FRCs support these interactions7,8. However, the molecular mechanisms that operate under physiological conditions remain unknown. Here we show that the viral protein m11, encoded by the herpesvirus murine cytomegalovirus (CMV), inhibits antiviral immunity by targeting the FRC network and interfering with a critical function of cellular CD44. We found that m11 binds to CD44 and established that m11 perturbs the molecular interactions of CD44 with its natural ligand, hyaluronic acid. The interaction of m11 with CD44 impairs the trafficking of dendritic cells within the spleen, thereby impeding efficient priming of naive T cells and the initiation of antiviral CD8 T cell responses. The targeting of CD44 by CMV reveals CD44 as a molecule that is essential to the functioning of the FRC network and uncovers a previously unrecognized stroma-based mechanism that is critical for the generation of effective T cell responses.

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.