Biology subjects

Lu, X.

Publications and source records attributed to Lu, X..

At least 163 records · Page 9Linked to original sources

bioRxiv2024

Rac1 and Nectin3 are essential for PCP-directed axon guidance in the peripheral auditory system

Our sense of hearing is critically dependent on the spiral ganglion neurons (SGNs) that connect the sound receptors in the organ of Corti (OC) to the cochlear nuclei of the hindbrain. Type I SGNs innervate inner hair cells (IHCs) to transmit sound signals, while type II SGNs (SGNIIs) innervate outer hair cells (OHCs) to detect moderate-to-intense sound. During development, SGNII afferents make a characteristic 90-degree turn toward the base of the cochlea and innervate multiple OHCs. It has been shown that the Planar Cell Polarity (PCP) pathway acts non-autonomously to mediate environmental cues in the cochlear epithelium for SGNII afferent turning towards the base. However, the underlying mechanisms are unknown. Here, we present evidence that PCP signaling regulates multiple downstream effectors to influence cell adhesion and the cytoskeleton in cochlear supporting cells (SCs), which serve as intermediate targets of SGNII afferents. We show that the core PCP gene Vangl2 regulates the localization of the small GTPase Rac1 and the cell adhesion molecule Nectin3 at SC-SC junctions through which SGNII afferents travel. Through in vivo genetic analysis, we also show that loss of Rac1 or Nectin3 partially phenocopied SGNII peripheral afferent turning defects in Vangl2 mutants, and that Rac1 plays a non-autonomous role in this process in part by regulating PCP protein localization at the SC-SC junctions. Additionally, epistasis analysis indicates that Nectin3 and Rac1 likely act in the same genetic pathway to control SGNII afferent turning. Together, these experiments identify Nectin3 and Rac1 as novel regulators of PCP-directed SGNII axon guidance in the cochlea. Significance statementPlanar Cell Polarity (PCP) signaling plays a non-autonomous role in the guidance of type II spiral ganglion neuron (SGNII) afferent projections that innervate cochlear hair cells. However, little is known about the underlying mechanisms. Here, we identify the small GTPase Rac1 and the cell adhesion molecule Nectin3 as two downstream effectors of PCP signaling in SGNII afferent guidance. We show that PCP signaling regulates Rac1 and Nectin3 localization in cochlear supporting cells that serve as intermediate targets for SGNII afferents and that Rac1 and Nectin3 likely act in the same genetic pathway to non-autonomously regulate SGNII afferent guidance. These findings significantly advance our understanding of auditory circuit assembly and shed light on PCP-directed axon guidance mechanisms.

developmental biology↗

bioRxiv2024

Prevention and treatment of noise-induced hearing loss and cochlear synapse degeneration by potassium channel blockers in vivo

Noise can induce hearing loss. In particularly, noise can induce cochlear synapse degeneration leading to hidden hearing loss, which is the most common type of hearing disorders in the clinic. Currently, there is no pharmacological treatment, particularly, no post-exposure (i.e., therapeutic) treatment available in the clinic. Here, we report that systematic administration of K+ channel blockers before or after noise exposure could significantly attenuate NIHL and synapse degeneration. After systematic administration of a general K-channel blocker tetraethylammonium (TEA), the elevation of auditory brainstem response (ABR) thresholds after noise-exposure significantly reduced, and the active cochlear mechanics significantly improved. The therapeutic effect was further improved as the post-exposure administration time extending to 3 days. BK channel is a predominant K+ channel in the inner hair cells. Systematic administration of a BK channel blocker GAL-021 after noise exposure also ameliorated hearing loss and improved hearing behavioral responses tested by acoustic startle response (ASR). Finally, both TEA and GAL-021 significantly attenuated noise-induced ribbon synapse degeneration. These data demonstrate that K+-channel blockers can prevent and treat NIHL and cochlear synapse degeneration. Our finding may aid in developing therapeutic strategies for post-exposure treatment of NIHL and synapse degeneration. Significance StatementNoise is a common deafness factor affecting more 100 million people in the United States. So far, there is no pharmacological treatment available. We show here that administration of K+ channel blockers after noise exposure could attenuate noise-induced hearing loss and synapse degeneration, and improved behavioral responses. This is the first time to real the K+ channel blockers that could treat noise-induced hearing loss and cochlear synaptopathy after noise exposure.

neuroscience↗

bioRxiv2024

Combinatorial Design Testing in Genomes with POLAR-seq

Synthetic biology projects increasingly use modular DNA assembly or synthetic in vivo recombination to generate diverse combinatorial libraries of genetic constructs for testing. But as these designs expand to multigene systems it becomes challenging to sequence these in a cost-effective way that reveals the genotype to phenotype relationships in the libraries. Here, we introduce a new quick, low-cost method designed for assessing combinational designs of genome-integrated multigene constructs that we call Pool of Long Amplified Reads (POLAR) sequencing. POLAR-seq takes genomic DNA isolated from library pools and uses long range PCR to amplify target genomic regions up to 35 kb long containing combinatorial designs. The pool of long amplicons is then directly read by nanopore sequencing with full length reads then used to identify the gene content and structural variation of individual genotypes in the library and read count indicating how abundant a genotype is within the pool. Using yeast cells with loxP-containing synthetic gene clusters that rearrange in vivo in the presence of Cre recombinase, we demonstrate how POLAR-seq can be used to identify global patterns from combinatorial experiments, find the most abundant genotypes in a pool and also be adapted to sequence-verify gene clusters from isolated strains.

synthetic biology↗

bioRxiv2024

Acute drug induced parkinsonian akinesia is associated with reduced rate and increased regularity of neuronal activity in the pedunculopontine tegmental nucleus of unanesthetized rats

The pedunculopontine tegmental nucleus of the brainstem is important for a wide range of functions, including sensorimotor integration and regulation of locomotion and discrete forelimb movements. Evidence suggests it is structurally disordered as part of the neuropathology of the movement disorder Parkinsons disease. To assess whether neuronal activity is also affected in parkinsonian model animals we used single neuron recordings in free moving rats to determine the effects of acute drug-induced parkinsonism on the firing rate of the neurons. Acute parkinsonian akinesia was associated with reduction in resting firing rate and increased firing regularity, consistent with reduced excitability in this state.

neuroscience↗

bioRxiv2024

Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Non-structural Proteins Inhibitors

The global coronavirus disease 2019 (COVID-19) pandemic persists, with the ongoing mutation of the virus. Consequently, the development of inhibitors with diverse binding modes and mechanisms of action, along with the elucidation of novel binding sites is of paramount importance. The 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro) are two validated cysteine proteases that cleave the viral polyprotein and are essential for viral replication. In this study, we utilized covalent DNA-Encoded libraries (CoDELs) workflow to identify two series of triazine-based covalent inhibitors targeting 3CLpro and PLpro. Molecular docking facilitated the identification of optimization pathways, further refined through medicinal chemistry efforts, leading to the development of the non-peptide 3CLpro inhibitor LU9, which exhibited an IC50 value of 0.34 M, and crystal structure of LU10 revealed a unique binding mode within the active site. Additionally, the X-ray cocrystal structure of SARS-CoV-2 PLpro with XD5 uncovered a previously unexplored binding site, adjacent to the catalytic pocket, providing an opportunity for further development of PLpro inhibitors. Overall, these novel compounds serve as valuable chemical probes for target validation and represent promising drug candidates for the continued development of SARS-CoV-2 antivirals.

biochemistry↗

bioRxiv2024

Sacrificing Adaptability for Functionality: The Ivory Tower of Macular Muller Cells

The predilection of many retinal diseases for the macula suggests it may be less resistant to stress than the peripheral retina. Profiling of single-cell level transcriptional changes found that the peripheral retina exhibited more transcriptional changes than the macula in response to stress. One pronounced change was in a subgroup of Muller cells (MCs) that were dominant in the peripheral retina. Genes more abundantly expressed in peripheral MCs were mainly associated with stress responses and were more influenced by light stress. In contrast, genes highly expressed in MCs that predominated in the macula had roles in cellular function and were less influenced by light stress. Metallothionein 1, A Kinase Anchor Protein 12 and MAF BZIP Transcription Factor F were more abundantly expressed in peripheral MCs than in macular MCs. Knockdown of these genes in primary MCs reduced their viability under stress. Our findings indicate that macular MCs are more directed toward maintaining retinal function rather than mounting a stress response when exposed to stress, which may contribute to the maculas vulnerability to degenerative diseases.

neuroscience↗

bioRxiv2024

Structural basis for the inhibition of coronaviral main proteases by PF-00835231

The main protease (Mpro) of coronaviruses plays a key role in viral replication, thus serving as a hot target for drug design. It has been proven that PF-00835231 is promising inhibitor of SARS-CoV-2 Mpro. Here, we report the inhibition potency of PF-00835231 against SARS-CoV-2 Mpro and seven Mpro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) from SARS-CoV-2 variants. The results confirm that PF-00835231 has broad-spectrum inhibition against various coronaviral Mpros. In addition, the crystal structures of SARS-CoV-2 Mpro, SARS-CoV Mpro, MERS-CoV Mpro, and seven SARS-CoV-2 Mpro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) in complex with PF-00835231 are solved. A detailed analysis of these structures reveal key determinants essential for inhibition and elucidates the binding modes of different coronaviral Mpros. Given the importance of the main protease for the treatment of coronaviral infection, structural insights into the Mpro inhibition by PF-00835231 can accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.

molecular biology↗

bioRxiv2024

CDHu40: a novel marker gene set of neuroendocrine prostate cancer (NEPC)

Prostate cancer (PCa) is the most prevalent cancer affecting American men. Castration-resistant prostate cancer (CRPC) can emerge during hormone therapy for PCa, manifesting with elevated serum prostate-specific antigen (PSA) levels, continued disease progression, and/or metastasis to the new sites, resulting in a poor prognosis. A subset of CRPC patients shows a neuroendocrine (NE) phenotype, signifying reduced or no reliance on androgen receptor (AR) signaling and a particularly unfavorable prognosis. In this study, we incorporated computational approaches based on both gene expression profiles and protein-protein interaction (PPI) networks. We identified 500 potential marker genes, which are significantly enriched in cell cycle and neuronal processes. The top 40 candidates, collectively named as CDHu40, demonstrated superior performance in distinguishing NE prostate cancer (NEPC) and non-NEPC samples based on gene expression profiles compared to other published marker sets. Notably, some novel marker genes in CDHu40, absent in the other marker sets, have been reported to be associated with NEPC in the literature, such as DDC, FOLH1, BEX1, MAST1, and CACNA1A. Importantly, elevated CDHu40 scores derived from our predictive model showed a robust correlation with unfavorable survival outcomes in patients, indicating the potential of the CDHu40 score as a promising indicator for predicting the survival prognosis of those patients with the NE phenotype. Motif enrichment analysis on the top candidates suggests that REST and E2F6 may serve as key regulators in the NEPC progression. Significanceour study integrates gene expression variances in multiple NEPC studies and protein-protein interaction network to pinpoint a specific set of NEPC maker genes namely CDHu40. These genes and scores based on their gene expression levels effectively distinguish NEPC samples and underscore the clinical prognostic significance and potential mechanism.

bioinformatics↗

bioRxiv2024

A role for δ subunit-containing GABA-A receptors on parvalbumin positive neurons in maintaining electrocortical signatures of sleep states

GABAA receptors containing {delta} subunits have been shown to mediate tonic/slow inhibition in the CNS. These receptors are typically found extrasynaptically and are activated by relatively low levels of ambient GABA in the extracellular space. In the mouse neocortex, {delta} subunits are expressed on the surface of some pyramidal cells as well as on parvalbumin positive (PV+) interneurons. An important function of PV+ interneurons is the organization of coordinated network activity that can be measured by EEG; however, it remains unclear what role tonic/slow inhibitory control of PV+ neurons may play in shaping oscillatory activity. After confirming a loss of functional {delta} mediated tonic currents in PV cells in cortical slices from mice lacking Gabrd in PV+ neurons (PV {delta}cKO), we performed EEG recordings to survey network activity across wake and sleep states. PV {delta}cKO mice showed altered spectral content of EEG during NREM and REM sleep that was a result of increased oscillatory activity in NREM and the emergence of transient high amplitude bursts of theta frequency activity during REM. Viral reintroduction of Gabrd to PV+ interneurons in PV {delta}cKO mice rescued REM EEG phenotypes, supporting an important role for {delta} subunit mediated inhibition of PV+ interneurons for maintaining normal REM cortical oscillations. Significance statementThe impact on cortical EEG of inhibition on PV+ neurons was studied by deleting a GABAA receptor subunit selectively from these neurons. We discovered unexpected changes at low frequencies during sleep that were rescued by viral reintroduction.

neuroscience↗

bioRxiv2024

Synthetic genome modules designed for programmable silencing of functions and chromosomes

Unlike in bacteria, eukaryotes rarely cluster sets of genes in their genomes according to function, instead having most genes spread randomly across different chromosomes and loci. However, with the advent of genome engineering, synthetic co-location of genes that together encode a cell function has now become possible. Here, using Saccharomyces cerevisiae we demonstrate the feasibility of reorganising a set of yeast genes encoding a cell function, tryptophan biosynthesis, into a synthetic genome module by deleting these genes and their regulatory elements from their native genomic loci while in parallel reconstructing them into gene cluster format by synthetic DNA assembly. As part of synthetic module design, loxPsym sequences recognised by Cre recombinase are placed between all module genes, and we leverage these for a novel master regulation system we call dCreSIR. Using dCreSIR we externally control silencing of synthetic modules by targeted binding of chromatin recruiters to loxPsym sites and this leads to inhibition of local transcription. We further show that dCreSIR can go beyond modules and be used to specifically downregulate expression across an entire synthetic yeast chromosome containing loxPsym sites. Together, our work offers insights into yeast genome organisation and establishes new principles and tools for the future design and construction of modular synthetic yeast genomes.

synthetic biology↗

bioRxiv2024

Transcriptional Determinism and Stochasticity Contribute to the Complexity of Autism Associated SHANK Family Genes

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3 mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We applied an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in human and mice. We unexpectedly discovered an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts were altered in Shank3 mutant mice and postmortem brains tissues from individuals with ASD. The enhanced SHANK3 transcriptome significantly improved the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest the stochastic transcription of genome associated with SHANK family genes.

genetics↗

bioRxiv2024

Dense, Continuous Membrane Labeling and Expansion Microscopy Visualization of Ultrastructure in Tissues

Lipid membranes are key to the nanoscale compartmentalization of biological systems, but fluorescent visualization of them in intact tissues, with nanoscale precision, is challenging to do with high labeling density. Here, we report ultrastructural membrane expansion microscopy (umExM), which combines a novel membrane label and optimized expansion microscopy protocol, to support dense labeling of membranes in tissues for nanoscale visualization. We validated the high signal-to-background ratio, and uniformity and continuity, of umExM membrane labeling in brain slices, which supported the imaging of membranes and proteins at a resolution of [~]60 nm on a confocal microscope. We demonstrated the utility of umExM for the segmentation and tracing of neuronal processes, such as axons, in mouse brain tissue. Combining umExM with optical fluctuation imaging, or iterating the expansion process, yielded [~]35 nm resolution imaging, pointing towards the potential for electron microscopy resolution visualization of brain membranes on ordinary light microscopes.

bioengineering↗

bioRxiv2024

A Spatial Multi-Modal Dissection of Host-Microbiome Interactions within the Colitis Tissue Microenvironment

The intricate and dynamic interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations to the intestinal tissue environment. Our ability to study these events on the systems level is significantly limited by in situ approaches capable of generating simultaneous insights from both host and microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for simultaneous in situ probing of host features and its microbiome across multiple spatial modalities. We demonstrate MicroCart by comprehensively investigating the alterations in both gut host and microbiome components in a murine model of colitis by coupling MicroCart with spatial proteomics, transcriptomics, and glycomics platforms. Our findings reveal a global but systematic transformation in tissue immune responses, encompassing tissue-level remodeling in response to host immune and epithelial cell state perturbations, and bacterial population shifts, localized inflammatory responses, and metabolic process alterations during colitis. MicroCart enables a deep investigation of the intricate interplay between the host tissue and its microbiome with spatial multiomics.

immunology↗

bioRxiv2024

Imaging and quantification of prostate cancer-associated bone by polarization-sensitive optical coherence tomography

Prostate cancer frequently metastasizes to bone, leading to a spectrum of osteosclerotic and osteolytic lesions that cause debilitating symptoms. Accurate differentiation of bone tissue or lesion types can provide opportunity for local pathologic investigation, which is critical for understanding the bone metastasis and remains challenging. Current imaging methods lack the ability to directly differentiate tissues based on collagen organization and may induce invasive effect on bone tissues. We introduce Polarization-Sensitive Optical Coherence Tomography (PS-OCT) to investigate normal, osteosclerotic, and osteolytic bone tissues. High-resolution PS-OCT imaging reveals collagen fiber arrangement, enabling nuanced distinction of degree of collagen alignment among different bone tissue types or regions. We present a novel feature named degree of ordered organization (DOO), derived from the multiple contrasts of PS-OCT that can quantitatively evaluate bone samples from different pathologic groups, including control,osteoblastic and osteolytic tissues. The capacity of PS-OCT to differentiate trabecular/lamellar and irregular (woven bone) regions within the same specimen is tested and validated on ex-vivo samples extracted from 13 subjects. Our study is the first time that PS-OCT is applied to metastatic bone disease with the aim of enhancing the understanding of bone-related pathologies, and potentially impacting clinical practice. This work demonstrates that PS-OCT can provide useful insight into bone microstructures, and thus it has potential applications across diverse bone disorders.

biophysics↗

bioRxiv2024

Novel 3-D macrophage spheroid model reveals reciprocal regulation of immunomechanical stress and mechano-immunological response

PurposeIn many diseases, an overabundance of macrophages contributes to adverse outcomes. While numerous studies have compared macrophage phenotype after mechanical stimulation or with varying local stiffness, it is unclear if and how macrophages themselves contribute to mechanical forces in their microenvironment. MethodsRaw 264.7 murine macrophages were embedded in a confining agarose gel, where they proliferated to form spheroids over time. Gels were synthesized at various concentrations to tune the stiffness and treated with various growth supplements to promote macrophage polarization. The spheroids were then analyzed by immunofluorescent staining and qPCR for markers of proliferation, mechanosensory channels, and polarization. Finally, spheroid geometries were used to computationally model the strain generated in the agarose by macrophage spheroid growth. ResultsMacrophages form spheroids and generate growth-induced mechanical forces (i.e., solid stress) within confining agarose gels, which can be maintained for at least 16 days in culture. Increasing agarose concentration restricts spheroid expansion, promotes discoid geometries, limits gel deformation, and induces an increase in iNOS expression. LPS stimulation increases spheroid growth, though this effect is reversed with the addition of IFN-{gamma}. Ki67 expression decreases with increasing agarose concentration, in line with the growth measurements. ConclusionsMacrophages alone both respond to and generate solid stress. Understanding how macrophage generation of growth-induced solid stress responds to different environmental conditions will help to inform treatment strategies for the plethora of diseases that involve macrophage accumulation.

immunology↗

bioRxiv2024

Blood flow regulates acvrl1 transcription via ligand-dependent Alk1 activity

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by the development of arteriovenous malformations (AVMs) that can result in significant morbidity and mortality. HHT is caused primarily by mutations in bone morphogenetic protein receptors ACVRL1/ALK1, a signaling receptor, or endoglin (ENG), an accessory receptor. Because overexpression of Acvrl1 prevents AVM development in both Acvrl1 and Eng null mice, enhancing ACVRL1 expression may be a promising approach to development of targeted therapies for HHT. Therefore, we sought to understand the molecular mechanism of ACVRL1 regulation. We previously demonstrated in zebrafish embryos that acvrl1 is predominantly expressed in arterial endothelial cells and that expression requires blood flow. Here, we document that flow dependence exhibits regional heterogeneity and that acvrl1 expression is rapidly restored after reinitiation of flow. Furthermore, we find that acvrl1 expression is significantly decreased in mutants that lack the circulating Alk1 ligand, Bmp10, and that BMP10 microinjection into the vasculature in the absence of flow enhances acvrl1 expression in an Alk1-dependent manner. Using a transgenic acvrl1:egfp reporter line, we find that flow and Bmp10 regulate acvrl1 at the level of transcription. Finally, we observe similar ALK1 ligand-dependent increases in ACVRL1 in human endothelial cells subjected to shear stress. These data suggest that Bmp10 acts downstream of blood flow to maintain or enhance acvrl1 expression via a positive feedback mechanism, and that ALK1 activating therapeutics may have dual functionality by increasing both ALK1 signaling flux and ACVRL1 expression.

developmental biology↗

bioRxiv2024

Evaluation of the potential food allergy risks of recombinant human lactoferrin expressed in Komagataella phaffii

Prior to the introduction of novel food ingredients into the food supply, safety risk assessments are required, and numerous prediction models have been developed and validated to evaluate safety. The allergenic risk potential of Helaina recombinant human lactoferrin (rhLF, Effera), produced in Komagataella phaffii (K. phaffii) was assessed by literature search, bioinformatics sequence comparisons to known allergens, glycan allergenicity assessment, and a simulated pepsin digestion model. The literature search identified no allergenic risk for Helaina rhLF, K. phaffii, or its glycans. Bioinformatics search strategies showed no significant risk for cross-reactivity or allergenicity between rhLF or the 36 residual host proteins and known human allergens. Helaina rhLF was also rapidly digested in simulated gastric fluid and its digestibility profile was comparable to human milk lactoferrin (hmLF), further demonstrating a low allergenic risk and similarity to the hmLF protein. Collectively, these results demonstrate a low allergenic risk potential of Helaina rhLF and do not indicate the need for further clinical testing or serum IgE binding to evaluate Helaina rhLF for risk of food allergy prior to introduction into the food supply.

immunology↗

bioRxiv2024

Feedback loop regulation between viperin and viral hemorrhagic septicemia virus through competing protein degradation pathways

Viperin is an antiviral protein that exhibits a remarkably broad spectrum of antiviral activity. Viperin-like proteins are found all kingdoms of life, suggesting it is an ancient component of the innate immune system. However, viruses have developed strategies to counteract viperins effects. Here, we describe a feedback loop between viperin and viral hemorrhagic septicemia virus (VHSV), a common fish pathogen. We show that Lateolabrax japonicus viperin (Ljviperin) is induced by both IFN-independent and IFN-dependent pathways, with the C-terminal domain of Ljviperin being important for its anti-VHSV activity. Ljviperin exerts an antiviral effect by binding both the nucleoprotein (N) and phosphoprotein (P) of VHSV and induces their degradation through the autophagy pathway, which is an evolutionarily conserved antiviral mechanism. However, counteracting viperins activity, N protein targets and degrades transcription factors that up-regulate Ljviperin expression, interferon regulatory factor (IRF) 1 and IRF9, through ubiquitin-proteasome pathway. Together, our results reveal a previously unknown feedback loop between viperin and virus, providing potential therapeutic targets for VHSV prevention. ImportanceViral hemorrhagic septicaemia (VHS) is a contagious disease caused by the viral hemorrhagic septicaemia virus (VHSV), which poses a threat to over 80 species of marine and freshwater fish. Currently, there are no effective treatments available for this disease. Understanding the mechanisms of VHSV-host interaction is crucial for preventing viral infections. Here, we found that, as an ancient antiviral protein, viperin degrades the N and P proteins of VHSV through the autophagy pathway. Additionally, the N protein also impacts the biological functions of IRF1 and IRF9 through the ubiquitin-proteasome pathway, leading to the suppression of viperin expression. Therefore, the N protein may serve as a potential virulence factor for the development of VHSV vaccines and screening of antiviral drugs. Our research will serve as a valuable reference for the development of strategies to prevent VHSV infections.

immunology↗