Biology subjects

Xu, C.

Publications and source records attributed to Xu, C..

At least 199 records · Page 11Linked to original sources

bioRxiv2023

Long noncoding RNAs and mRNAs profiling in ovary during laying and broodiness in Taihe Black-Bone Silky Fowls (Gallus gallus domesticus Brisson)

Broodiness is one of the important factors affecting poultry egg production, with the black-bone Silky (Gallus gallus domesticus Brisson) exhibiting strong broodiness behavior. Changes in ovarian signaling can offer insights into the mechanisms influencing broodiness. However, research comparing the characteristics of long non- coding RNAs (lncRNAs) in the ovaries during the broody chickens (BC) and high egg- laying chickens (GC) groups of poultry is still limited. In this study, we employed RNA-seq to analyze the ovarian transcriptomes (lncRNAs and mRNAs) of eight brooding and high egg-laying Taihe Black-Bone Silky Fowls (TBsf). We identified a total of 16,444 mRNAs and 18,756 lncRNAs, among which 349 mRNAs and 651 lncRNAs (P < 0.05) showed significantly different expression (DE) between the BC and GC groups. Additionally, we identified the cis-regulated and trans-regulated target genes of differentially abundant lncRNA transcripts and constructed an lncRNA- mRNA trans-regulated interaction network associated with ovarian follicle development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses revealed that DE mRNAs and target genes of DE lncRNAs were associated with neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, Cytokine-cytokine receptor interaction, and ECM-receptor interaction pathways. Our study provides a catalogue of lncRNAs and mRNAs related to ovarian development and constructs a predicted interaction network of differentially abundant lncRNAs and Differentially Expressed Genes (DEGs) in TBsf, thus enhancing our understanding of the interactions between lncRNAs and genes regulating brooding behavior. Author summaryIn this study, we performed transcriptome sequencing analysis of the ovaries from BC and GC groups in TBsf. A total of 349 significantly differentially expressed mRNAs and 651 significantly differentially expressed lncRNAs were detected. Furthermore, we identified 10 key genes that may affect reproductive performance in chickens: STC1, MMP13, IL8, AT2, FSHB, RARB, THOC7, FGF12, EPHA1, and NPY5R. Based on GO and KEGG enrichment analyses, we preliminarily explored five pathways that may influence egg production performance: neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, cytokine-cytokine receptor interaction and ECM-receptor interaction. These genes and pathways may play crucial roles in improving broodiness behavior. This study establishes a foundation for subsequent screening of candidate functional genes and functional validation of important production traits in TBsf, providing a theoretical basis for further molecular breeding and enhancing egg-laying performance in TBsf.

bioinformatics↗

bioRxiv2023

Phylogenomic analyses support a new infrageneric classification of Pourthiaea (Maleae, Rosaceae) using multiple inference methods and extensive taxon sampling

In this comprehensive study, we conducted extensive taxon sampling and performed phylogenomic analyses based on plastome and nuclear ribosomal DNA (nrDNA) datasets. We employed multiple inference methods, including concatenated and coalescent-based strategies, to generate an accurate phylogeny of the woody Rosaceae genus Pourthiaea. The nrDNA phylogeny of Pourthiaea strongly supported three major clades, which were consistent with morphology. However, the plastid tree provided an alternative phylogenetic topology, indicating cytonuclear discordance. Frequent hybridizations between and among the species of Pourthiaea could explain the cytonuclear discordance. Considering the evidence from morphology and phylogenomic data, we propose a new infrageneric classification for Pourthiaea, consisting of three sections: P. sect. Pourthiaea, P. sect. Amphidoxae B.B.Liu, and P. sect. Impressivenae B.B.Liu.

plant biology↗

bioRxiv2023

OBMeta: a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases

Gut dysbiosis is closely associated with obesity and related metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). The gut microbial features and biomarkers have been increasingly investigated in recent studies, which require further validation due to the limited sample size and various confounding factors that may affect microbial compositions. So far, it lacks a comprehensive bioinformatics pipeline providing automated statistical analysis and integrating independent studies for cross validation simultaneously. OBMeta aims to streamline the standard metagenomics data analysis from diversity analysis, comparative analysis, functional analysis, to co-abundance network analysis. In addition, a curated database has been established with a total of 88 public research projects, covering three different phenotypes (Obesity, T2D, and NAFLD) and more than five different intervention strategies (exercise, diet, probiotics, medication, and surgery). With OBMeta, users can not only analyze their own research projects, but also search and match public datasets of interest for cross-project validation. Moreover, OBMeta provides cross-phenotype and cross-intervention-based advanced validation that maximally supports preliminary findings from an individual study. To summarize, OBMeta is a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases. OBMeta is freely available at: http://obmeta.met-bioinformatics.cn/. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=82 SRC="FIGDIR/small/552363v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1b58a9borg.highwire.dtl.DTLVardef@19efa47org.highwire.dtl.DTLVardef@418597org.highwire.dtl.DTLVardef@1a9bc3c_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

A versatile framework for drug-target interaction prediction by considering domain specific features

Predicting drug-target interaction (DTI) is a critical and rate-limiting step in drug discovery. Traditional wet-lab experiments are reliable but expensive and time-consuming. Recently, deep learning has revealed itself as a new and promising tool for accelerating the DTI prediction process because its powerful performance. Due to the vast chemical space, the DTI prediction models are typically expected to discover drugs or targets that are absent from the training set. However, generalizing prediction performance to novel drug-target pairs that belong to different distributions is a challenge for deep learning methods. In this work, we propose an Ensemble of models that capture both Domain-generIc and domain-Specific features (E-DIS) to learn diversity domain features and adapt to out-of-distribution (OOD) data. We employed Mixture-of-Experts (MOE) as a domain-specific feature extractor for the raw data to prevent the loss of any crucial features by the encoder during the learning process. Multiple experts are trained on different domains to capture and align domain-specific information from various distributions without accessing any data from unseen domains. We evaluate our approach using four benchmark datasets under both in-domain and cross-domain settings and compare it with advanced approaches for solving OOD generalization problems. The results demonstrate that E-DIS effectively improves the robustness and generalizability of DTI prediction models by incorporating diversity domain features.

bioinformatics↗

bioRxiv2023

PSTPIP2 ameliorates aristolochic acid nephropathy by suppressing interleukin-19-mediated neutrophil extracellular trap formation

Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by herbal medicines. Previously, we found that proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) and neutrophil extracellular traps (NETs) play important roles in kidney injury and immune defense, respectively; however, the mechanism of AAN regulation by PSTPIP2 and NETs remains unclear. We found that renal tubular epithelial cell (RTEC) apoptosis, neutrophil infiltration, and inflammatory factor and NET production were increased in a mouse model of AAN, while PSTPIP2 expression was low. Conditional knock-in of PSTPIP2 in mouse kidneys inhibited cell apoptosis, reduced neutrophil infiltration, suppressed the production of inflammatory factors and NETs, and ameliorated renal dysfunction. In contrast, restoring normal PSTPIP2 expression promoted kidney injury. In vivo, the use of Ly6G-neutralizing antibody to remove neutrophils and peptidyl arginine deiminase 4 (PAD4) inhibitors to prevent NET formation reduced apoptosis, thereby alleviating kidney injury. In vitro, damaged RTECs released interleukin-19 (IL-19) via the PSTPIP2/nuclear factor (NF)-{kappa}B pathway and induced NET formation via the IL-20R{beta} receptor. Concurrently, NETs promoted the apoptosis of damaged RTECs. PSTPIP2 affected NET formation by regulating IL-19 expression via inhibition of NF-{kappa}B pathway activation in RTECs, inhibiting their apoptosis and reducing kidney damage.

pharmacology and toxicology↗

bioRxiv2023

Rapid identification of key genes for the rod-shaped morphology in bacteria using multi-species genomes

Accurate identification of key genes is pivotal in biological research. Here, we introduce machine learning to the field of functional gene identification, enabling precise prediction of bacterial shape based on genomic information. Our machine learning model successfully predicts bacterial shape, and we determine the influence of various protein domains on shape using the model. This approach facilitates the identification of candidate genes involved in regulating bacterial shape. Through targeted knockout experiments on eight potential key regulatory genes (pal, yicC, mreB, tolQ, ftsX, amiC, yddB, and rpoZ) in Escherichia coli, we observe significant alterations in rod-shaped morphology upon individual knockout of pal and mreB genes. E. coli transitions from rod-shaped to spherical or cell wall-deficient protoplasmic states. Experimental validations validate the robustness of our newly developed method. This study establishes an innovative avenue for exploring functional genes, harnessing large-scale genomic information to promptly uncover key genes governing shared traits across species.

genetics↗

bioRxiv2023

Improving the Circularization Efficiency, Stability and Translatability of Circular RNA by circDesign

Synthetic circular RNA (circRNA) has emerged as a promising platform for vaccine and therapeutic development, featuring its uniqueness in a closed-loop structure, cap-independent translation mechanism, and prolonged expression. However, the rational design of a circRNA sequence to jointly improve its stability and protein coding potential remains challenging. In this study, we present circDesign, an efficient algorithm to achieve the optimal design of circRNA by ensuring optimized folding of each segment, which leads to enhanced circularization efficiency, stability, and translatability. Using rabies virus glycoprotein (RABV-G) as the model antigen, we demonstrated that circDesign-generated circRNAs exhibited higher stability and protein translation efficiency in vitro and in vivo compared to other codon adaptation index (CAI)-optimized sequences, thus leading to enhanced in vivo immunogenicity. Ribosome and polysome profiling further revealed that an intact internal ribosome entry site (IRES) structure is critical for efficient translation. By intentionally disrupting the IRES motifs, we observed that the resulting circRNA sequences had lower translatability compared to circDesign-generated sequences. Taken together, our circular RNA design algorithm provides a general strategy to leverage the capability of circRNA as next-generation vaccines or therapeutics.

bioengineering↗

bioRxiv2023

Engineering transposon-associated TnpB-1 ωRNA system for efficient gene editing and disease treatment in mouse

Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (409 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB in mouse embryos was already higher than previously identified small-sized Cas12f1. Further stepwise engineering of noncoding RNA ({omega}RNA or reRNA) component of TnpB significantly elevated the nuclease activity of TnpB. Notably, an optimized TnpB-{omega}RNA system could be efficiently delivered in vivo with single adeno-associated virus (AAV) and prevented the disease phenotype in a tyrosinaemia mouse model. Thus, the engineered miniature TnpB system represents a new addition to the current genome editing toolbox, with the unique feature of the smallest effector size that facilitate efficient AAV delivery for editing of cells and tissues.

molecular biology↗

bioRxiv2023

Strong epistasis constrains the evolution of strict substrate specificity in apicomplexan lactate dehydrogenases

The homologous enzymes lactate and malate dehydrogenase (L/MDH) are structurally similar but are specific for different substrates. LDH vs MDH specificity is canonically governed by the identity of a single "specificity residue" at position 102. However, LDH function has convergently evolved from a specific MDH at least four times, and the catalytic role of residue 102 is not conserved between different phyla. The apicomplexa are a phylum of obligate, intracellular eukaryotic parasites responsible for wide-spread disease such as Plasmodium falciparum (malaria), Cryptosporidium parvum (cryptosporidiosis), Toxoplasma gondii (toxoplasmosis), and Eimeria maxima (eimeriosis). The apicomplexan LDH evolved via a five-residue insertion that produced a novel specificity residue, W107f. The commonly accepted mechanism of LDH specificity involves charge balance and steric occlusion, but our data shows that the general mechanism of apicomplexan LDHs does not use W107f as a steric block. Only Plasmodium LDHs evolved substantial steric specificity, making them exceptional among Apicomplexa. Strong protein epistasis constrained this evolution, making it difficult to revert to ancestral phenotypes. Here, we use ancestral sequence reconstruction (ASR), steady-state kinetics, and x-ray crystallography to characterize apicomplexan LDHs which challenge current assumptions about the evolution of L/MDH activity. We demonstrate the unique specificity of Plasmodium LDHs and identify the active site residues controlling their substrate recognition. The extraordinarily high specificity of Plasmodium LDHs presents difficulties for small-molecule inhibitor development, and successful drugs against Plasmodium LDH may not be efficacious against other Apicomplexa LDHs and their diseases.

evolutionary biology↗

bioRxiv2023

Notch signaling and Bsh homeodomain activity are integrated to diversify Drosophila lamina neuron types

Notch signaling is an evolutionarily conserved pathway for specifying binary neuronal fates, yet how it specifies different fates in different contexts remains elusive. In our accompanying paper, using the Drosophila lamina neuron types (L1-L5) as a model, we show that the primary homeodomain transcription factor (HDTF) Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates. Here we test the hypothesis that Notch signaling enables Bsh to differentially specify L4 and L5 fates. We show asymmetric Notch signaling between newborn L4 and L5 neurons, but they are not siblings; rather, Notch signaling in L4 is due to Delta expression in adjacent L1 neurons. While Notch signaling and Bsh expression are mutually independent, Notch is necessary and sufficient for Bsh to specify L4 fate over L5. The NotchON L4, compared to NotchOFF L5, has a distinct open chromatin landscape which allows Bsh to bind distinct genomic loci, leading to L4-specific identity gene transcription. We propose a novel model in which Notch signaling is integrated with the primary HDTF activity to diversify neuron types by directly or indirectly generating a distinct open chromatin landscape that constrains the pool of genes that a primary HDTF can activate.

developmental biology↗

bioRxiv2023

High-resolution structure of mouse radial spoke and its in-situ structure in ependymal cilia revealed by cryo-EM and cryo-ET

Radial spokes (RS) transmit mechanochemical signals between the central pair (CP) and axonemal dynein arms to coordinate ciliary motility. However, the high-resolution structure of mammalian RS remains missing. Here, we present the high-resolution cryo-EM structure of mouse RS head-neck complex in both monomer and dimer forms and reveal the intrinsic dynamics of the dimer. We also map the genetic mutations related to primary ciliary dyskinesia and asthenospermia on the head-neck complex. Moreover, we present the unprecedented cryo-ET and sub-tomogram averaging map of mouse ependymal cilia, whose beating creates unidirectional cerebrospinal fluid flow, and build the models for RS1-3, IDAs, and N-DRC. Strikingly, our cryo-ET map reveals the lack of IDA-b/c/e and the absence of tektin filaments within the A-tubule of doublet microtubules in ependymal cilia compared with mammalian respiratory cilia and sperm flagella. This tissue-specific feature may represent an evolutionary choice driven by the functional requirements on ependymal cilia. Our findings reveal the RS head-neck assembly mechanism, shed light on the coordinated rigid and elastic RS-CP interaction modes beneficial for the regulation of asymmetric ciliary beating, and also facilitate understandings on the etiology of ciliary dyskinesia-related ciliopathies.

biophysics↗

bioRxiv2023

Neo-functionalization and co-option of Pif genes facilitate the evolution of a novel shell microstructure in oysters

Molluscan shell, composed of a diverse range of architectures and microstructures, is a classic model system to study the relationships between molecular evolution and biomineralized structure formation. The shells of oysters differ from those of other molluscs by possessing a novel microstructure, chalky calcite, which facilitates adaptation to the sessile lifestyle. However, the genetic basis and evolutionary origin of this adaptive innovation remain largely unknown. Here, we present the first chromosome-level genome and shell proteomes of the Iwagaki oyster Crassostrea nippona. Multi-omic integrative analyses revealed that independently evolved and co-opted genes as well as lineage-specific domains are involved in the formation of chalky layer in the oysters. Rapid mineralization involving chalky calcite are essential for reconstruction of the shell. Importantly, von Willebrand factor type A and chitin-binding domains are identified as basic members of molluscan biomineralization toolkit. We show that the well-known Pif shared a common origin in the last common ancestor of Bilateria. Furthermore, Pif and LamG3 genes acquire new genetic function for shell mineralization in bivalves and the chalky layer formation in oysters through a combination of gene duplication and domain reorganization. Our findings highlight neo-functionalization as a crucial mechanism for shell diversity, which may be applied more widely for studies on the evolution of metazoan biomineralization. This study also has potential implications for material science and biomimetic research.

evolutionary biology↗

bioRxiv2023

Dynamic enhancer interactome promotes senescence and aging

Gene expression programs are regulated by enhancers which act in a context-specific manner, and can reside at great distances from their target genes. Extensive three-dimensional (3D) genome reorganization occurs in senescence, but how enhancer interactomes are reconfigured during this process is just beginning to be understood. Here we generated high-resolution contact maps of active enhancers and their target genes, assessed chromatin accessibility, and established one-dimensional maps of various histone modifications and transcription factors to comprehensively understand the regulation of enhancer configuration during senescence. Hyper-connected enhancer communities/cliques formed around genes that are highly expressed and within essential gene pathways in each cell state. In addition, motif analysis indicates the involvement of specific transcription factors in hyper-connected regulatory elements in each condition; importantly, MafK, a bZIP family transcription factor, was upregulated in senescence, and reduced expression of MafK ameliorated the senescence phenotypes. Because the accumulation of senescent cells is a key feature of aging, we further investigated enhancer connectomes in the liver of young and aged mice. Hyper-connected enhancer communities were identified during aging, which regulate essential genes that maintain cell differentiation and homeostasis. These findings reveal that hyper-connected enhancer communities correlate with high gene expression in senescence and aging and provide potential hotspots for therapeutic intervention in aging and age-associated diseases.

molecular biology↗

bioRxiv2023

PlantC2U: Deep learning of cross-species sequence landscapes predicts plastid C-to-U RNA editing in plants

In plants, C-to-U RNA editing is mainly occurred in the plastids and mitochondria transcripts, which contributes to complex transcriptional regulatory network. More evidences reveal that RNA editing plays critical roles in plant growth and development. However, RNA editing sites accurately detected by transcriptome sequencing data alone are still challenging. In the present study, we developed PlantC2U, which is a convolutional neural network to predict plastid C-to-U RNA editing based on the genomic sequence. PlantC2U achieves over 95% sensitivity and 99% specificity, which outperforms random forest and support vector machine. PlantC2U not only further checks RNA editing sites from transcriptome data to reduce the possible false positives, but also assesses the effect of different mutations on C-to-U RNA editing status based on the flanking sequences. Moreover, we found the patterns of tissue-specific RNA editing in mangrove plant Kandelia obovata, and observed reduced C-to-U RNA editing rates in cold stress response of K. obovata, suggesting their potential regulatory roles in the plants stress adaption. In addition, we present RNAeditDB, available online at https://jasonxu.shinyapps.io/RNAeditDB/. Together, PlantC2U and RNAeditDB would help researchers explore the RNA editing events in plants and thus would be of broad utility for the plant research community. HighlightWe develop a convolutional neural network based deep learning, PlantC2U program, which help researchers explore the plastids C-to-U RNA editing events in plants and thus would be of broad utility for the plant research community.

bioinformatics↗

bioRxiv2023

A novel bacterial signal transduction system specifically senses and responds to peptidoglycan damage

The peptidoglycan (PG) layer is a mesh-like structure within the cell envelope essential for maintenance of cell shape and resistance to osmotic stress, and therefore is a primary target of many important and widely used antibiotics, such as {beta}-lactams. In Gram-negative bacteria, while signal transduction systems that monitor the state of the inner- and outer-membranes have been extensively studied and well understood, much less is known about how cells sense and respond to PG-targeting stresses. Here we show that a novel bacterial two-component system (PghKR) from Shewanella oneidensis is capable of sensing and responding to PG damage. This system is specifically activated in cells exposed to various PG-targeting antibiotics or carrying a defect in PG synthesis, resulting in induced expression of blaA and relV, which encode a {beta}-lactamase conferring resistance to {beta}-lactams and a small ppGpp synthetase responsible for antibiotic tolerance, respectively. Intriguingly, the PghKR homologs are widespread among several classes of Proteobacteria and the periplasmic domain of sensor kinase PghK contains a family 9 carbohydrate-binding module that is required for signal perception, implying that the signals could be the glycan fragments of PG. Overall, our results provide critical insights into the regulation of PG homeostasis in Gram-negative bacteria.

microbiology↗

bioRxiv2023

Automatic cell type harmonization and integration across Human Cell Atlas datasets

Harmonizing cell types across the single-cell community and assembling them into a common framework is central to building a standardized Human Cell Atlas. Here we present CellHint, a predictive clustering tree-based tool to resolve cell type differences in annotation resolution and technical biases across datasets. CellHint accurately quantifies cell-cell transcriptomic similarities and places cell types into a relationship graph that hierarchically defines shared and unique cell subtypes. Application to multiple immune datasets recapitulates expert-curated annotations. CellHint also reveals underexplored relationships between healthy and diseased lung cell states in eight diseases. Furthermore, we present a workflow for fast cross-dataset integration guided by harmonized cell types and cell hierarchy, which uncovers underappreciated cell types in adult human hippocampus. Finally, we apply CellHint to 12 tissues from 38 datasets, providing a deeply curated cross-tissue database with [~]3.7 million cells and various machine learning models for automatic cell annotation across human tissues.

bioinformatics↗

bioRxiv2023

Spatiotemporal transcriptome atlas of human embryos after gastrulation

The spatial and temporal atlas of gene expression in the human embryo at early gestation is critical in understanding embryo development, organogenesis, and disease origins. We obtained the spatiotemporal transcriptome from 90 sagittal sections of 16 whole human embryos from 3 to 8 post-conception weeks by Stereo-seq with high resolution and ultra-large field, establishing the development trajectory/regulatory profiling of 49 organs. We uncovered the organ-specific regulons as potential lineage-determining factors and identified the new regulatory networks during heart and brain development. The atlas refines the key organs/cell types vulnerable to virus infection and genetic disorders, and, reveals the dynamics of allelic gene expression in specific organs at different stages. These results present the first comprehensive delineation of the spatiotemporal transcriptomic dynamics of human organogenesis. One Sentence SummaryThe spatiotemporal transcriptome atlas presents a comprehensive delineation of human embryogenesis after gastrulation.

developmental biology↗

bioRxiv2023

Interferon epsilon restricts Zika virus infection in the female reproductive tract

Interferon {varepsilon} (IFN{varepsilon}) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections (STIs). Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFN{varepsilon} contributes to protection against ZIKV infection in vivo is unknown. Here, we show that IFN{varepsilon} plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFN{varepsilon} was expressed not only by epithelial cells in the FRT, but also by certain immune and other cells at baseline or after exposure to viruses or specific TLR agonists. IFN{varepsilon}-deficient mice exhibited abnormalities in the epithelial border and underlying tissue in the cervicovaginal tract, and these defects were associated with increased susceptibility to vaginal, but not subcutaneous ZIKV infection. IFN{varepsilon}-deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFN{varepsilon} protected Ifn{varepsilon}-/- mice and highly susceptible Ifnar1-/-mice against vaginal ZIKV infection, indicating that IFN{varepsilon} was sufficient to provide protection even in the absence of signals from other type I IFNs and in an IFNAR1-independent manner. Our findings reveal a potentially critical role for IFN{varepsilon} in mediating protection against transmission of ZIKV in the context of sexual contact. SignificanceInterferon {varepsilon} (IFN{varepsilon}), a unique Type I IFN that is highly expressed in the epithelium of the female reproductive tract (FRT), is thought to protect the host against sexually transmitted infections (STIs) but the mechanism of action is not defined. Zika virus (ZIKV), a causative agent for preterm birth and other severe diseases in pregnant women, can be spread through vaginal transmission. Here, we show that mice lacking the Ifn{varepsilon} gene have abnormal epithelial development and tissue architecture in the cervicovaginal tract. The role of IFN{varepsilon} in protecting host against ZIKV is FRT-specific and is independent of IFNAR1 signaling. Our findings suggest potential preventive strategies based on harnessing mucosal immunity against STIs.

immunology↗