Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “host antiviral immunity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2025

African Swine Fever Virus MGF 360-2L Disrupts Host Antiviral Immunity Based on Transcriptomic Analysis.

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.

African swine fever virus↗
PubMed1978

In irradiation chimeras, K or D regions of the chimeric host, not of the donor lymphocytes, determine immune responsiveness of antiviral cytotoxic T cells.

The H-2 haplotype of the chimeric host determines the responder phenotype of maturing T cells. Spleen cells of chimeric mice formed when (K(k) nonresponder to D(b) x K(b) responder to D(b) plus vaccinia)F(1) bone marrow cells were used to reconstitute K(b)D(b) (C57BL/6 D(b) responder) irradiated recipients generated high levels of D(b) plus vaccinia virus-specific cytotoxic T cells. The same stem cells used to reconstitute K(k)D(b) (B10.A (2R) D(b) nonresponder) irradiated recipients resulted in spleen cells that responded well to K plus vaccinia, but responsiveness to D(b) was low. A generally low response to D(k) plus vaccinia, which seems to be regulated by D(k), was confirmed in chimeras. Thus, K(d)D(d) (D(d) plus vaccinia responder) stem cells differentiating in a K(d)D(k) chimeric host failed to generate a measurable response to D(k) plus vaccinia. In contrast, stem cells from K(d)D(k) (D(k) plus vaccinia low responders) differentiating in a K(d)D(d) (K(d) and D(d) high responders to vaccinia) host do generate responsiveness to D(d) plus vaccinia. These results indicate that in chimeras, the Ir phenotype is independent of the donor T cell's Ir genotype, and that thymic selection of a T cell's restriction specificity for a particular H-2 allele of the chimeric host also defines that T cell's/r phenotype.

Animals↗
PubMed2026

PRRSV suppresses FTO-dependent m6A demethylation to reprogram STAT signaling and innate immunity.

RNA viruses have evolved diverse strategies to evade host interferon (IFN)-stimulated gene (ISG) defenses; however, how they exploit host epitranscriptomic regulation remains poorly understood. Here, we identify an immune-evasion mechanism in which porcine reproductive and respiratory syndrome virus (PRRSV) targets the m6A demethylase fat mass and obesity-associated protein (FTO) to suppress antiviral signaling. Mechanistically, the viral endoribonuclease nsp11 inhibits STAT5-dependent transcription through the key residues Q96 and S104, thereby reducing FTO expression. Loss of FTO increases m6A modification of STAT2 and STAT3 transcripts, impairing their translation and phosphorylation, thereby attenuating ISG responses. Reduced STAT3 activity further dampens STAT5 signaling, establishing a feed-forward circuit that amplifies suppression of antiviral immunity. Functionally, disruption of this regulatory region (Q96A and S104A) attenuates viral pathogenicity in vivo and restores ISG induction. These mutations also reduce infection-associated inflammatory responses and the accumulation of reactive oxygen species. Together, these findings define a nsp11-STAT5-FTO-STAT2/3 axis that enables PRRSV to reprogram host epitranscriptomic control of innate immunity. Our work reveals a mechanism of epitranscriptomic hijacking and identifies FTO as a key host factor exploited by RNA viruses, highlighting m6A regulation as a potential target for antiviral intervention.IMPORTANCEViruses must overcome host innate immune defenses to establish infection; however, the mechanisms by which they manipulate host RNA regulation remain incompletely understood. In this study, we show that porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon responses by targeting the host m6A demethylase FTO through its endoribonuclease nsp11. This process involves the inhibition of STAT5 phosphorylation, which reduces FTO expression and increases m6A modification of key immune regulators, including STAT2 and STAT3, thereby impairing their activation. Disruption of this pathway attenuates viral pathogenicity in vivo and restores antiviral signaling. These results demonstrate that PRRSV can reprogram host epitranscriptomic regulation to modulate innate immunity and suggest that m6A-related pathways may be potential targets for antiviral intervention.

Immunity, Innate↗
PubMed2025

Induction of tunnelling nanotube-like structures by influenza A viruses requires the onset of apoptosis.

As well as spreading through virions, influenza A viruses (IAVs) can evade antiviral drugs and neutralising antibodies by spreading directly from cell to cell. In cell culture this can occur by the induction of intercellular membrane connections known as tunnelling nanotube-like structures (TLSs), which are capable of trafficking the viral genome between cells. Here, we showed that TLSs are formed by IAV infected cells in vivo, and then used in vitro models to ask how IAVs induce their formation. We found that TLS formation is not induced by cytokine signalling from infected to uninfected cells, but induction does require intracellular IAV replication. IAV replication can form filamentous virions which have structural similarities to TLSs, but we found that TLS induction is independent of virion morphology. We therefore looked at the intracellular responses to infection and found that the induction of TLSs correlated with the induction of apoptosis. Furthermore, the ability of IAVs to drive TLS formation can be modulated by chemically inhibiting, or inducing apoptosis. Finally, we found that inhibiting apoptosis, which prevents IAVs from inducing TLSs, lead to a significant reduction in the ability of IAVs to directly spread between cells. Our results, which suggest that IAVs can control their ability to spread directly from cell to cell by driving infected cells into apoptosis, identifies a new way in which a virus can manipulate its host to evade antiviral immune responses.

Apoptosis↗
PubMed2026

A small viral protein suppresses immune amplification by two distinct mechanisms.

Diverse viral suppressors of RNA interference (RNAi) and RNA silencing (VSRs) interact directly with core protein and/or RNA components of the host RNAi pathway. However, the specific counter-defense function of any VSR biochemical activity is fully validated only when it is shown as essential for viral infection in the wild-type but not mutant hosts defective in antiviral RNAi. Here, we investigated the role of VSR activities for direct binding to small-interfering RNA duplexes (siRNA), long double-stranded RNA (dsRNA), or RNA-dependent RNA polymerase 1 (RDR1) during plant infection by wild-type and mutant cucumber mosaic virus (CMV), a positive-strand RNA virus expressing the 110-residue 2b protein as its VSR. We demonstrate that a C-terminally truncated 2b mutant (2b1-93) active in direct binding to siRNA and dsRNA, but not RDR1, was able to suppress the amplification of virus-derived siRNAs (vsiRNA) and antiviral RNAi mediated by RDR6, but not RDR1. By contrast, an N-terminally truncated 2b mutant (2b18-110) inactive in direct binding to siRNA or dsRNA was able to suppress vsiRNA amplification and antiviral RNAi mediated by RDR1, but not RDR6, and was less effective to promote systemic CMV infection and disease development than 2b1-93. Together, our results show that whereas RDR1 suppression requires direct binding of VSR-2b to RDR1, but not siRNA or dsRNA, RDR6 suppression depends on direct binding to siRNA and dsRNA, but not RDR1. Therefore, CMV, through its VSR-2b, suppresses two parallel vsiRNA amplification pathways by distinct molecular mechanisms, and this unique property may account for the unusually wide host range of CMV.IMPORTANCEHost amplification of antiviral immunity is essential for robust control of viral infections. However, little is known about the mechanisms that viruses have evolved to suppress immune amplification in plants. Here, we characterized whole plant infection by cucumber mosaic virus (CMV) with its viral suppressor of RNA interference (RNAi) mutated to become inactive in direct binding to small-interfering RNA duplexes (siRNA), long double-stranded RNA (dsRNA), or RNA-dependent RNA polymerase 1 (RDR1). We demonstrate maximal suppression of both RDR1- and RDR6-mediated antiviral RNAi amplification by the CMV 2b protein, a viral suppressor of RNAi (VSR). Notably, whereas RDR1 suppression requires direct binding of 2b to RDR1 but not siRNA or dsRNA, RDR6 suppression depends on direct binding to siRNA and dsRNA, but not RDR1. Our findings reveal a novel counter-defense strategy evolved by a wide host range positive-strand RNA virus to suppress two pathways of immune amplification by distinct mechanisms.

Cucumovirus↗
PubMed2026

AP2: an indispensable host factor in virus infection.

Adaptor protein complex 2 (AP2), a central regulator of clathrin-mediated endocytosis and intracellular cargo trafficking, is hijacked by numerous viruses to complete their infectious cycles. This review systematically synthesizes the multifaceted roles of AP2 across the entire viral life cycle, from entry and replication to assembly and release, as well as in immune evasion. By delineating how diverse viruses exploit this key host machinery, we further consolidate the rationale and current progress in developing broad-spectrum antiviral strategies that target AP2 and its regulatory pathways. This work aims to provide a unified perspective on AP2 as a critical host-pathogen interface, offering new insights into viral pathogenesis and antiviral drug discovery.

Humans↗
PubMed1977

Interaction of adenine arabinoside and host defense factors in experimental infections due to Herpesvirus hominis.

The role of host immune functions in relation to the antiviral effects of adenine arabinoside (ara-A) and/or humoral antibodies in Herpesvirus hominis infection was studied in four different mouse models (newborn Swiss mice, three-week-old Swiss mice, athymic nude [nu/nu] mice, and phenotypically normal [nu/+] littermates of nude mice). Although the overall beneficial effects afforded by the administration of ara-A and/or humoral antibodies were similar, the degree of protection varied among the four host systems. The data indicate that host defense factors play an important role in modulating the effect of humoral antibodies and/or an antiviral agent. Combined use of ara-A and humoral antibodies resulted in enhanced protection against H. hominis infection. Our data suggest that control of viral infection, particularly in compromised hosts, may require chemoimmunotherapy.

Animals↗
PubMed2026

The Adaptive Roles of Active Transposable Elements in Insect Hosts.

Active transposable elements (TEs) are capable of generating new insertions in genomes and have historically been viewed as genomic parasites due to their largely detrimental or neutral effects. However, emerging evidence suggests that these elements also play a crucial role in driving adaptive evolution in insects. This mini-review synthesizes recent findings on how active TEs contribute to insect adaptation through various mechanisms, including regulation of gene expression, structural variation, and epigenetic effects. Notable examples of adaptation driven by active TEs include their roles in insecticide resistance, morphological adaptations, tolerance to harsh climates, and antiviral immune responses. We argue that while host silencing mechanisms, such as the piRNA pathway, tightly regulate TE activity to minimize harmful effects, the context-dependent activation of active TEs can generate beneficial genetic variation that enhances insect adaptations to anthropogenic and climatic pressures. Future research that integrates long-read sequencing, single-cell omics, and gene editing techniques will provide a robust mechanistic foundation for understanding the adaptive significance of active TEs in insects, with important implications for pest management, pollinator protection, and evolutionary biology.

Journal Article↗
PubMed2026

PTBP1 at the host-virus interface: mechanistic roles in viral RNA translation, replication, and immune modulation.

Viruses require the involvement of host RNA binding proteins for completion of important steps of their life cycle. Polypyrimidine tract binding protein 1 (PTBP1) is an RNA-binding protein found ubiquitously which performs important regulatory functions like alternative splicing, RNA stability, RNA localization, and translation by virtue of its four RRMs and shuttling between nucleus and cytoplasm. There is increasing evidence showing that many viruses make use of such regulatory roles of PTBP1 to facilitate their gene expression and replication. This review describes the existing mechanistic knowledge about the PTBP1 functions during viral infection, paying attention to the role of PTBP1 in viral RNA translation, viral RNA genome replication, and regulation of host antiviral response. Special attention is paid to the regulation by PTBP1 of IRES-dependent translation of enteroviruses and hepatitis C virus, as well as to the PTBP1 contribution to RNA stabilization, long-distance RNA interactions, and genome cyclization of flaviviruses such as dengue virus and Japanese encephalitis virus. Recent data on the PTBP1 function in coronavirus RNA metabolism are discussed as well. Furthermore, the role of PTBP1 in being both proviral and antiviral is reviewed in terms of innate immunity signalling pathways, stress granule biology, and virus-host interaction. Finally, we will explore the possibility of PTBP1 being used as a host-directed antiviral drug target despite the hurdles in doing so considering its multifunctionality as an essential cellular RNA-binding protein.

Polypyrimidine Tract-Binding Protein↗
PubMed2026

Influence of Major Histocompatibility Complex (MHC) Diversity on Immune Modulation, Pathogenesis, and Control of Lumpy Skin Disease Virus.

INTRODUCTION: Lumpy Skin Disease Virus (LSDV), a member of the genus Capripoxvirus within the family Poxviridae, is an economically important transboundary viral pathogen affecting cattle and water buffalo. The disease causes severe production losses through decreased milk yield, infertility, hide damage, reduced growth performance, and occasional mortality. The rapid geographic spread of LSDV, together with its vectorborne transmission and emerging recombinant strains, has intensified the need for improved understanding of viral pathogenesis, host immune responses, and effective prevention strategies. In particular, the role of the bovine Major Histocompatibility Complex (BoLA/MHC) in regulating antiviral immunity, disease susceptibility, and vaccine responsiveness has gained increasing scientific attention. METHODS: This review summarises the published literature related to the epidemiology, transmission, structure, pathogenesis, diagnosis, prevention, and control of LSDV, with special emphasis on the immunological and molecular role of bovine MHC molecules. Relevant studies concerning BoLA-mediated antigen presentation, immunoinformaticsbased epitope prediction, vaccine development, antiviral drug repurposing, molecular docking, genomic surveillance, and diagnostic approaches, including PCR- and ELISAbased assays, were critically evaluated. Recent advances in computational biology, molecular virology, and host-pathogen interaction studies were also reviewed. RESULTS: The reviewed studies demonstrate that Lumpy Skin Disease Virus (LSDV) possesses a complex double-stranded DNA genome enabling immune modulation and efficient transmission through arthropod vectors such as mosquitoes, ticks, and biting flies. Disease progression involves systemic viral replication, vascular injury, dermal necrosis, and inflammatory skin lesions. Real-time PCR remains the most sensitive diagnostic method for early detection, while ELISA supports surveillance. Evidence highlights the central role of bovine Major Histocompatibility Complex (BoLA) molecules in antigen presentation and T-cell activation. Computational studies identified promising BoLA-binding epitopes and repurposed antiviral candidates, including ivermectin, theaflavin, canagliflozin, and tepotinib, for future therapeutic development. DISCUSSION: Current evidence indicates that effective LSDV control requires integration of molecular diagnostics, vector management, vaccination, and host immunogenetics. BoLAguided immunoinformatics provides promising opportunities for developing multi-epitope vaccines, although experimental validation remains essential. Similarly, repurposed antiviral candidates require comprehensive in vivo and pharmacological evaluation before clinical application. Future research should focus on elucidating viral immune-evasion mechanisms, validating predicted epitopes, and translating computational findings into practical vaccines and therapeutics for sustainable disease control. CONCLUSION: Lumpy Skin Disease continues to pose a major threat to global cattle health and livestock economies. Advances in molecular diagnostics, genomic surveillance, antiviral drug discovery, and BoLA-guided vaccine design provide promising opportunities for improved disease control. Understanding the interaction between LSDV and the bovine MHC system is essential for developing next-generation vaccines, immunotherapeutics, and precision disease-management strategies. Future research should prioritise experimental validation of predicted epitopes, large-scale vaccine trials, and mechanistic studies on host-virus immune interactions to establish effective and sustainable global control programs for LSDV.

BoLA↗
PubMed2026

Rasputin/G3BP mediates subversion of antiviral immunity by o'nyong-nyong virus in Anopheles coluzzii.

Cellular G3BP proteins are essential for alphavirus infection in both vertebrate and mosquito hosts, but the underlying mechanism of their proviral activity is poorly understood in any host. Whether the mosquito G3BP ortholog, Rasputin (Rin), interacts with host immunity to influence alphavirus infection has not been investigated, and anopheline mosquito interactions with arboviruses have been little studied. Here, we find that Rin silencing in Anopheles mosquitoes results in decreased ONNV infection levels, indicating a proviral activity for Anopheles Rin. We find that Rin function is required to maintain basal activity of the antiviral Imd and JAK/STAT pathways in uninfected mosquitoes. However, during ONNV infection, the control of the Imd pathway by Rin activity appears corrupted because Rin silencing leads to overexpression of the Imd positive regulator, Rel2. Thus, silencing of Rin both augments Rel2 transcript abundance and decreases ONNV load. Co-silencing of Rel2 with Rin restores normal ONNV infection levels, indicating that Rin activity is required to inhibit Imd function during ONNV infection, and which explains most of the Rin proviral phenotype. In addition, we show that the ONNV non-structural protein 3 (nsP3), which binds to Rin, strongly alters the pattern of Anopheles cellular protein partners interacting with Rin. In the presence of ONNV nsP3, 48 Rin-binding host proteins are unchanged but seven binding proteins are excluded and eight new cellular proteins bind Rin. The altered cellular protein partners are candidate host factors involved in viral subversion of Rin control over Imd activity. Overall, these results reveal a molecular mechanism in which ONNV, probably through nsP3, co-opts the normal Rin function for basal cellular immune activity by subverting the Imd antiviral pathway to promote infection. These results may be generalizable for Rin function during alphavirus infection of other mosquitoes, as well as for G3BP function in the mammalian host, and could offer a target for development of vector-based genetic control tools against arbovirus transmission.

Animals↗
PubMed2026

Tobamoviruses: Advances in Molecular Biology, Host Interactions and Integrated Disease Management.

Tobamoviruses (viruses in the genus Tobamovirus, family Virgaviridae) lead to major yield losses in economically important crops around the world. In this review, we go beyond the canonical gene expression framework by integrating recent discoveries of reverse open reading frames (rORFs) on the negative-strand RNA. These rORFs have only been experimentally validated in cucumber green mottle mosaic virus (CGMMV), with predicted sequence-conserved homologs across a subset of the genus, including TMV, ToBRFV, and PMMoV. However, they are not universally present in all tobamoviruses. We systematically dissect the infection cycle-from disassembly and replication to cell-to-cell and systemic movement-with an emphasis on the host factors hijacked at each stage. We synthesize current understanding of plant antiviral immunity, focusing on RNA silencing and NLR receptor-mediated resistance as two pillars of defense, along with the transcription factors and microRNAs that orchestrate these responses. We critically evaluate the experimental evidence for both plant defenses and viral counter-strategies, noting that many mechanistic models derive from limited model systems. We further characterize host genetic resistance and susceptibility factors applicable to crop breeding. These resources include dominant NLR and non-NLR resistance, as well as recessive resistance derived from modified host susceptibility genes. We address how viral mutations, recombination and fitness trade-offs undermine resistance durability. We then evaluate their practical deployment through conventional breeding, the exploitation of quantitative resistance, and genome editing, and outline associated agronomic drawbacks and regulatory constraints. Using ToBRFV as a case study, we analyze its epidemiological traits and assess the current arsenal of surveillance tools, from field diagnostics to remote sensing. Finally, we survey management strategies across a spectrum of maturity. Some approaches, including sanitation protocols and conventionally bred resistant cultivars, have proven effective under field conditions. The first dsRNA-based biopesticide has recently been registered in China, while other biological control agents and low-risk chemical approaches remain largely at the experimental stage. We also discuss the bottlenecks that impede lab-to-field transition and highlight promising solutions such as precision breeding and evolution-oriented cultivar deployment. By bridging molecular virology, epidemiology, and integrated disease management, this review provides a critical, bench-to-field framework for the sustainable control of tobamoviruses.

TMV↗
PubMed2026

NAT10 is critical to block RNA sensing-induced IFN-β transactivation in viral infection.

UNLABELLED: Cells detect invading viruses and produce type I interferons (IFNs) to stimulate an innate antiviral effector response. However, IFN levels must be fine-tuned to achieve antiviral efficacy while limiting hyperinflammatory and tissue-damaging effects. Here, we report that NAT10, a histone and cytidine acetyltransferase, regulates the production of type I IFNs and RNA virus infections. Depletion of NAT10 increased the expression of IFN-β and IFN-stimulated genes, and correspondingly impaired viral replication. Mechanistically, NAT10 dynamically associated with the IFN-β promoter and also negatively regulated IRF3's chromatin associations through modulation of long noncoding RNAs that inhibit IRF3. Treatment of cells with Remodelin, a NAT10 inhibitor, similarly increased IFN-β expression and inhibited viral infections. Overall, our findings reveal NAT10 is a potential host-directed target for antiviral treatment via regulation of type I IFN. IMPORTANCE: Type I interferons (IFNs) signaling pathway is critical to cellular defense and innate immunity against evading pathogens, including viruses. However, induction of type I IFNs is fine-tuned to achieve the antiviral consequence while maintaining host cellular homeostasis. This paper presents a novel mechanism for the NAT10 protein to silence IFN-β induction through modulation of IRF3 activity at the promoter of IFN-β, and further demonstrates the therapeutic potential of the NAT10 inhibitor Remodelin to restrict viral infection while inducing IFN-β.

Interferon-beta↗
PubMed2026

SARS-CoV-2 Orf3a protein interaction mapping using unnatural amino acid incorporation.

Mapping transient protein-protein interactions remain a major challenge in studying viral host-pathogen interfaces. While some virus-host interactions are stable and readily captured, the majority are highly dynamic, reflecting the need for viral proteins to engage distinct host factors at different stages of the life cycle. Here, we employ a protein engineering strategy based on the site-specific incorporation of the unnatural acid p-azido-L-phenylalanine (AzF) to enable photo-crosslinking proteomic analysis of the SARS-CoV-2 accessory protein Orf3a in live cells. Genetic installation of AzF at residue K198 of Orf3a permitted UV-induced covalent capture of proximal host interacting proteins, overcoming challenges associated with membrane localization and limited protein abundance. A total of 248 high-confidence Orf3a-interacting proteins were reproducibly identified and subjected to gene ontology analysis, revealing enrichment in innate immune signaling, antiviral defense, RNA processing, and viral replication-associated pathways. Orf3a is an accessory protein that functions as a viroporin and traffics across multiple cellular compartments, and was found to interact with host RNA helicases, RNA-binding proteins, immune regulators, and metabolic enzymes implicated in SARS-CoV-2 infection. Together, these results demonstrate that genetically encoded, site-specific photo-crosslinking enables selective capture of transient interactions that are often missed by nonspecific 254 nm UV crosslinking approaches and highlights Orf3a as a multifunctional protein that engages diverse host pathways. More broadly, this study establishes a generalizable framework for leveraging unnatural amino acid-based protein engineering approaches to interrogate dynamic host-pathogen interactions.

Humans↗
PubMed2025

Evolution of antiviral host defenses against a backdrop of endogenous retroelements.

Mammalian hosts deploy a multitude of germ line-encoded mechanisms to detect and restrict virus infection. These mechanisms must avoid pathological responses to endogenous retroviruses and other endogenous retrotransposable elements (RTEs)-viruses and viruslike genomic parasites that have invaded the host germ line and are passed down the generations as host genes. Although the location, specificity, and sensitivity of innate pattern recognition receptors and restriction factors are tuned to facilitate discrimination of infecting viruses from those that are part of self, immune cross-reactions do occur. The RTE viral heritage may, therefore, compromise the ability of the host to respond to virus infection without risking pathology. Nevertheless, RTEs have the potential to be co-opted as an alarm amplification system, to be repurposed as antiviral factors, and to contribute to the evolution of antiviral genes.

Animals↗
PubMed2026

Host-interferon-stimulated gene response to virus-host recombinant variants of hepatitis E virus and enhanced viral replication.

The hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. HEV infection can become chronic in immunocompromised individuals, in whom virus-host recombinant variants (VHRVs) can be detected. These variants often harbor host-derived insertions in the polyproline-rich region (PPR), and most display enhanced replication in vitro. However, the mechanisms underlying this replicative advantage remain unclear. It is likely that genes of the infected cells are differentially expressed according to the replicative capacity of the strain. The host factors involved in the improvement of the replicative capacity of these VHRVs are yet to be identified.In this study, we analyzed the host transcriptional response to seven VHRVs in HepG2/C3A cells using bulk RNA sequencing at 48 h and 168 h post-infection. Five VHRVs (RNF19A, ZNF787, KIF1B, RPS17, EEF1A1) previously associated with a high replication rate induced more significant, distinct transcriptomic changes than low-replicative variants (RNA18, RPL6), particularly at 168 h. A shared set of 25 genes, especially interferon-stimulated genes (ISGs), was upregulated in cells infected with high-replicating variants. Interestingly, ISG induction was limited at 48 h despite high viral RNA concentrations, suggesting a delayed antiviral response. At 168 h, high ISG expression coincided with high viral loads, indicating that VHRVs may evade or exploit immune defenses. Our findings reveal candidate ISGs such as IFIT1 and ISG15 that may influence HEV persistence and immune escape. These results offer new insights into the interplay between VHRV replication and host immunity.IMPORTANCEHepatitis E virus (HEV) is a major cause of acute hepatitis and can cause chronic infections in immunocompromised individuals. Virus-host recombinant variants (VHRVs) having integrated host-derived insertions often replicate more effectively, yet the host determinants of this phenotype remain unclear. With RNA sequencing of HepG2/C3A-infected cells, we observed that high-replicating VHRVs induce a delayed but strong expression of interferon-stimulated genes (ISGs), including IFIT1 and ISG15, despite high viral loads. These results suggest that VHRVs may transiently modulate or evade aspects of host antiviral defenses. Our study revealed host transcriptional patterns associated with enhanced viral replication, providing insight into potential mechanisms that enhance HEV replication and highlighting candidate pathways that could influence the interplay between viral replication and immune responses, all requiring further investigation.

Humans↗
PubMed2026

Crown ethers as artificial decoys: A supramolecular strategy to block SARS-CoV-2 entry via host-guest interactions.

Coronavirus disease (COVID-19) remains a major global health challenge, highlighting the need for antiviral strategies that act at the earliest stages of infection. Given that viral entry and spike-receptor interaction are critical steps in the coronavirus life cycle, targeting these processes represents a powerful strategy to block infection at its earliest stage. Inspired by the glycan-recognition and extracellular viral-trapping functions of pulmonary surfactant collectins (SP-A and SP-D), this work integrates supramolecular chemistry, pulmonary surfactant biology, and antiviral research to establish a biomimetic supramolecular molecular-decoy framework based on crown ethers, cyclodextrins, and related macrocyclic architectures. Through host-guest molecular recognition, these macrocyclic scaffolds can be engineered to mimic sialylated host receptors and multivalent glycan motifs, enabling competitive binding to viral spike proteins, virion capture, and sequestration away from epithelial surfaces. By redirecting viruses toward artificial host-mimetic structures, supramolecular decoys could intercept SARS-CoV-2 and other enveloped respiratory viruses before host-cell attachment, membrane fusion, or genome release. Acting upstream of intracellular replication, this strategy may prevent initiation of the viral replication cycle and subsequent hijacking of the host protein synthesis machinery, while potentially minimizing interference with host metabolic pathways and reducing the likelihood of resistance development. Furthermore, it can be translated into inhalation nanoformulations for pulmonary delivery and localized formulations targeting the upper respiratory tract. Overall, by integrating the biological principles of pulmonary surfactant immunity with supramolecular host-guest chemistry, this work provides a conceptual foundation for biomimetic molecular-decoy antivirals and highlights a promising direction for next-generation broad-spectrum antiviral design against emerging respiratory viruses.

Antiviral Agents↗
PubMed2026

Bacterially produced dsRNA targeting SePGRP-LB reduces population fitness of Spodoptera exigua (Lepidoptera: Noctuidae) and increases its susceptibility to SeMNPV.

The beet armyworm, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), is an important agricultural pest, and S. exigua multiple nucleopolyhedrovirus (SeMNPV) is a host-specific biological control agent. However, baculovirus efficacy can be limited by host antiviral responses. S. exigua peptidoglycan recognition protein LB (SePGRP-LB) has been identified as an antiviral immune factor, suggesting that its suppression may increase larval susceptibility to SeMNPV. In this study, bacterially produced double-stranded RNA targeting SePGRP-LB (bac-dsPGRP-LB) was orally delivered to larvae to induce RNA interference. Feeding bac-dsPGRP-LB reduced SePGRP-LB transcript levels by 24.0% to 65.7% over 7 d. SePGRP-LB knockdown prolonged fifth-instar larval development, reduced female pupal weight, shortened male adult longevity and the oviposition period, and decreased fecundity by approximately 51%. Life table analysis further showed significant reductions in the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R0) following bac-dsPGRP-LB treatment. During SeMNPV infection, co-feeding with bac-dsPGRP-LB significantly suppressed SePGRP-LB expression, increased the SeMNPV genomic load, and reduced larval survival compared with the SeMNPV + bac-dsGFP treatment. These findings identify SePGRP-LB as a promising RNAi target for simultaneously reducing S. exigua fitness and enhancing its susceptibility to SeMNPV under laboratory conditions.

SePGRP-LB↗