Biology subjects

Hao, J.

Publications and source records attributed to Hao, J..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Origin and stepwise improvement of vertebrate lungs

Lungs, essential for terrestrial vertebrates and present in bony fishes but absent in cartilaginous fishes, provide an ideal model for studying organ origination. Our study analyzed single-cell RNA sequencing data from mature and developing vertebrate lungs, revealing substantial similarities in cell composition, developmental trajectories and gene expression pattern across species. Notably, most lung-related genes are also present in cartilaginous fishes, indicating that gene presence alone does not guarantee lung development. We identified thousands of lung regulatory elements specific to bony fishes, with higher concentrations around genes such as tbx4 and the hoxb gene cluster. These regulatory changes might contribute to lung emergence as well as the unique co-expression patterns in lung epithelial cells, such as those related to pulmonary surfactants and cell morphology. Our research also revealed that AT1 cells are specific to mammals, and we identified a mammal-specific gene, sfta2. Knockout experiments demonstrated that sfta2 deletion causes severe respiratory defects in mice, underscoring its critical role in specialized mammalian lungs. In conclusion, our results demonstrate that the origin and evolution of lungs are driven by a complex interplay of regulatory network modifications and the emergence of new genes, underscoring the multifaceted nature of organ evolution.

evolutionary biology↗

bioRxiv2024

Cellular and Molecular Changes During Aging in MEC: Unveiling the Role of Bglap3 Neurons in Cognitive Aging

Aging-correlated cognitive declines, including deficiencies in spatial orientation and memory, may reflect dysfunction in the hippocampus and medial entorhinal cortex (MEC). However, aging-related changes in MEC at the cellular and molecular levels remain unclear. In this study, we found fewer grid cells with reduced spatial stability in old mice. We compared gene expression profiles between young and old mice using 10x Genomics Visium technology. Among 1664 differentially expressed genes, we discovered Bglap3, a marker gene for subpopulation in MEC Layer III with decreased cell number with age. Silencing of Bglap3+ neurons in young mice impaired the spatial tuning of neurons in MEC and the spatial learning of a new platform location in water maze. These findings help us to understand the cellular and molecular changes in the MEC in healthy aging animals and the changes of Bglap3+ cells in old mice indicating a possible cause of aging-related MEC deficiency.

neuroscience↗

bioRxiv2024

Identifying potential risk genes for clear cell renal cell carcinoma with deep reinforcement learning

Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of renal cell carcinoma. However, our understanding of ccRCC risk genes remains limited. This gap in knowledge poses significant challenges to the effective diagnosis and treatment of ccRCC. To address this problem, we propose a deep reinforcement learning-based computational approach named RL-GenRisk to identify ccRCC risk genes. Distinct from traditional supervised models, RL-GenRisk frames the identification of ccRCC risk genes as a Markov decision process, combining the graph convolutional network and Deep Q-Network for risk gene identification. Moreover, a well-designed data-driven reward is proposed for mitigating the lim-itation of scant known risk genes. The evaluation demonstrates that RL-GenRisk outperforms existing methods in ccRCC risk gene identification. Additionally, RL-GenRisk identifies ten novel ccRCC risk genes. We successfully validated epidermal growth factor receptor (EGFR), corroborated through independent datasets and biological experimentation. This approach may also be used for other diseases in the future.

bioinformatics↗

bioRxiv2024

Development of a humanized anti-FABP4 monoclonal antibody for treatment of breast cancer

BackgroundBreast cancer, lung cancer, and colorectal cancer are the primary contributors to newly diagnosed cases among women, with breast cancer representing the second highest proportion of the total. The treatment protocols vary depends on different stages of breast cancer, and numerous clinical trials are ongoing based on the data derived from laboratory. Our studies demonstrate that circulating adipose fatty acid binding protein (A-FABP, or FABP4) links obesity-induced dysregulated lipid metabolism and breast cancer risk, thus offering a new target for breast cancer treatment. MethodsWe immunized FABP4 knockout mice with recombinant human FABP4 and screened hybridoma clones with specific binding to FABP4. The potential effects of antibodies on breast cancer cells in vitro were evaluated using migration, invasion, and limit dilution assays. Tumor progression in vivo was evaluated in various types of tumorigenesis models including C57BL/6 mice, Balb/c mice, and SCID mice. The phenotype and function of immune cells in tumor microenvironment were characterized with multi-color flow cytometry. Tumor stemness was detected by ALDH assays. To characterize antigen-antibody binding capacity, we determined the dissociation constant of S-V9 against FABP4 via surface plasmon resonance. Further analyses in tumor tissue were performed using 10X Genomics Visium spatial single cell technology. ResultsHerein, we report the generation of humanized monoclonal antibodies blocking FABP4 activity for breast cancer treatment in mouse models. One clone, named 12G2, which significantly reduced circulating levels of FABP4 and inhibited mammary tumor growth, was selected for further characterization. After confirming the therapeutic efficacy of the chimeric 12G2 monoclonal antibody consisting of mouse variable regions and human IgG1 constant regions, 16 humanized 12G2 monoclonal antibody variants were generated by grafting its complementary determining regions to selected human germline sequences. Humanized V9 monoclonal antibody showed consistent results in inhibiting mammary tumor growth and metastasis by affecting tumor cell mitochondrial metabolism. ConclusionsOur current evidence suggest that targeting FABP4 with humanized monoclonal antibodies represents a novel strategy for the treatment of breast cancer and possibly other obesity- associated diseases.

cancer biology↗

bioRxiv2024

The impact of Arctic environments on human cerebral blood flow

BackgroundThe Arctic environment represents an extreme living condition that has significant impact on life. But research on alterations of human cerebral blood flow (CBF) in a high-latitude and low-temperature environment in the Arctic is still lacking. MethodsMembers of the 12th Chinese National Arctic Research Expedition team who took the icebreaker R/V Xuelong 2 to the Arctic were recruited. Transcranial colour doppler (TCD) examination was performed at the beginning of the voyage (lower latitude and higher temperature, LLHT) and during the Arctic scientific expedition period (higher latitude and lower temperature, HLLT) respectively. The spectral pattern and parameters of cerebral arteries were compared. ResultsAmong 16 healthy individuals, 13 completed the TCD examination twice. They had a significantly lower mean velocity (Vm) (63.5 cm/s HLLT vs. 68.4cm/s LLHT; P=0.028) and peak systolic velocity (PSV) (94.6cm/s HLLT vs. 107.0cm/s LLHT; P=0.038) of the left middle cerebral artery (LMCA) and higher pulsatility index (PI) of the right middle cerebral artery (RMCA) (0.83 HLLT vs. 077 LLHT; P=0.011) in the HLLT environment compared to the LLHT one. ConclusionsChanges in human CBF may occur in higher-latitude and lower-temperature environments in the Arctic.

physiology↗

bioRxiv2023

Group-common and individual-specific effects of structure-function coupling in human brain networks with graph neural networks

The human cerebral cortex is organized into functionally segregated but synchronized regions bridged by the structural connectivity of white matter pathways. While structure-function coupling has been implicated in cognitive development and neuropsychiatric disorders, it remains unclear to what extent the structure-function coupling reflects a group-common characteristic or varies across individuals, at both the global and regional brain levels. By leveraging two independent, high-quality datasets, we found that the graph neural network accurately predicted unseen individuals functional connectivity from structural connectivity, reflecting a strong structure-function coupling. This coupling was primarily driven by network topology and was substantially stronger than that of the correlation approaches. Moreover, we observed that structure-function coupling was dominated by group-common effects, with subtle yet significant individual-specific effects. The regional group and individual effects of coupling were hierarchically organized across the cortex along a sensorimotor-association axis, with lower group and higher individual effects in association cortices. These findings emphasize the importance of considering both group and individual effects in understanding cortical structure-function coupling, suggesting insights into interpreting individual differences of the coupling and informing connectivity-guided therapeutics.

neuroscience↗

bioRxiv2023

A foundation model for bioactivity prediction using pairwise meta-learning

Compound bioactivity plays an important role in different stages of drug development and discovery. Existing machine learning approaches have poor generalization ability in compound bioactivity prediction due to the small number of compounds in each assay and incompatible measurements among assays. Here, we propose ActFound, a foundation model for bioactivity prediction trained on 2.3 million experimentally-measured bioactivity compounds and 50, 869 assays from ChEMBL and BindingDB. The key idea of ActFound is to employ pairwise learning to learn the relative value differences between two compounds within the same assay to circumvent the incompatibility among assays. ActFound further exploits meta-learning to jointly optimize the model from all assays. On six real-world bioactivity datasets, ActFound demonstrates accurate in-domain prediction and strong generalization across datasets, assay types, and molecular scaffolds. We also demonstrated that ActFound can be used as an accurate alternative to the leading computational chemistry software FEP+(OPLS4) by achieving comparable performance when only using a few data points for fine-tuning. The promising results of ActFound indicate that ActFound can be an effective foundation model for a wide range of tasks in compound bioactivity prediction, paving the path for machine learning-based drug development and discovery.

bioinformatics↗

bioRxiv2023

An uncanonical CDK6 activity inhibits cilia function by suppressing axoneme polyglutamylation

Tubulin polyglutamylation is a post-translational modification that occurs primarily along the axoneme of cilia. Defective axoneme polyglutamylation impairs cilia function and has been correlated with ciliopathies, including Joubert Syndrome (JBTS). However, the precise mechanisms regulating proper axoneme polyglutamylation remain vague. Here, we show that Cyclin-Dependent Kinase 6 (CDK6), but not its paralog CDK4, localizes to cilia base and suppresses axoneme polyglutamylation by phosphorylating RAB11-interacting protein FIP5 at site S641, a critical regulator of cilia import of glutamylases. S641 phosphorylation disrupts the ciliary recruitment of FIP5 by impairing its association with RAB11, thereby reducing the ciliary import of glutamylases. Interestingly, significant upregulation of CDK6 and defective axoneme polyglutamylation were observed in Autosomal dominant polycystic kidney disease (ADPKD) cells. Encouragingly, the FDA-approved CDK4/6 inhibitor Abemaciclib can effectively restore cilia function in JBTS and ADPKD cells with defective glutamylation and suppresses renal cystogenesis in an ex vivo ADPKD model. In summary, our study elucidates regulatory mechanisms governing axoneme polyglutamylation and suggests developing CDK6-specific inhibitors could be a promising therapeutic strategy to enhance cilia function in ciliopathy patients.

cell biology↗

bioRxiv2023

Generating human neural diversity with a multiplexed morphogen screen in organoids

Morphogens choreograph the generation of remarkable cellular diversity in the developing nervous system. Differentiation of stem cells toward particular neural cell fates in vitro often relies upon combinatorial modulation of these signaling pathways. However, the lack of a systematic approach to understand morphogen-directed differentiation has precluded the generation of many neural cell populations, and knowledge of the general principles of regional specification remain in-complete. Here, we developed an arrayed screen of 14 morphogen modulators in human neural organoids cultured for over 70 days. Leveraging advances in multiplexed RNA sequencing technology and annotated single cell references of the human fetal brain we discovered that this screening approach generated considerable regional and cell type diversity across the neural axis. By deconvoluting morphogen-cell type relationships, we extracted design principles of brain region specification, including critical morphogen timing windows and combinatorics yielding an array of neurons with distinct neuro-transmitter identities. Tuning GABAergic neural subtype diversity unexpectedly led to the derivation of primate-specific interneurons. Taken together, this serves as a platform towards an in vitro morphogen atlas of human neural cell differentiation that will bring insights into human development, evolution, and disease.

neuroscience↗

bioRxiv2023

DNA double-strand break-capturing nuclear envelope tubules drive DNA repair

The nuclear envelope is a membrane separating nuclear from cytoplasmic processes. Existing models suggest that damaged DNA moves to the envelope at the edge of the nucleus for repair. Yet, most damaged human DNA does not reposition to the nuclear periphery during repair. Here we show that human cells relocate the nuclear envelope to non-peripheral damaged DNA, providing solid support promoting the reconnection of DNA break ends. Upon DNA double-strand break (DSB) induction, cytoplasmic microtubules poke the nuclear envelope inwards, inducing an extensive network of DSB-capturing nuclear envelope tubules (dsbNETs). The formation of dsbNETs, which encompass the nuclear lamina and the inner and outer nuclear membranes, depends on DNA damage response kinases, dynamic microtubules, the linker of the nucleoskeleton and cytoskeleton (LINC) proteins SUN1 and SUN2, nuclear pore protein NUP153, and kinesin KIF5B. Repressing dsbNETs compromises the reassociation of DSB ends. The timely reversal of dsbNETs by the kinesin KIFC3 also promotes repair. DSB ends reconnection is restored in dsbNETs-deficient cells by enlarging the 53BP1 DNA repair center. The lamina-binding domain of SUN1 mediates its entry into the tubules and DSB capture by the envelope. Fusing truncated SUN1 to the NHEJ repair protein KU70 fails to localize SUN1 to the tubules but rescues DSB targeting only to the boundary envelope. Although dsbNETs typically promote accurate DSB repair and cell survival, they are co-opted by the PARP inhibitor olaparib to induce aberrant chromosomes restraining BRCA1-deficient breast cancer cells. We uncover dsbNETs, which bring the nuclear envelope to DSBs for repair and potentiate the efficacy of anti-cancer agents. Our findings revise theories of the structure-function relationship of the nuclear envelope and identify dsbNETs as a critical factor in DNA repair and nuclear organization, with implications for health and disease.

molecular biology↗

bioRxiv2023

Protein Sequence Design by Entropy-based Iterative Refinement

Inverse Protein Folding (IPF) is an important task of protein design, which aims to design sequences compatible with a given backbone structure. Despite the prosperous development of algorithms for this task, existing methods tend to leverage limited and noisy residue environment when generating sequences. In this paper, we develop an iterative sequence refinement pipeline, which can refine the sequence generated by existing sequence design models. It selects and retains reliable predictions based on the models confidence in predicted distributions, and decodes the residue type based on a partially visible environment. The proposed scheme can consistently improve the performance of a number of IPF models on several sequence design benchmarks, and increase sequence recovery of the SOTA model by up to 10%. We finally show that the proposed model can be applied to redesign Transposon-associated transposase B. 8 variants exhibit improved gene editing activity among the 20 variants we proposed. Our code and a demo of the refinement pipeline are provided in the online colab.

bioinformatics↗

bioRxiv2023

Unraveling the causal genes and transcriptomic determinants of human telomere length

Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogated TL-modulated genes and their potential functions. We found that placental TL is relatively longer across human tissues and which maintenance is mostly connected to genes responsible for alternative lengthening of telomeres. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identified 20 novel genetic associations and provided increased polygenic determination of human TL. Next, we integrated the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 31 likely causal genes, among which 4 were functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improved the prediction performance of human TL. This study deepened our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.

genetics↗

bioRxiv2023

Discovering SARS-CoV-2 neoepitopes and the associated TCR-pMHC recognition mechanisms by combining single-cell sequencing, deep learning, and molecular dynamics simulation techniques

The molecular mechanisms underlying the recognition of epitopes by T cell receptors (TCRs) are critical for activating T cell immune responses and rationally designing TCR-based therapeutics. Single-cell sequencing techniques vastly boost the accumulation of TCR sequences, while the limitation of available TCR-pMHC structures hampers further investigations. In this study, we proposed a comprehensive strategy that incorporates structural information and single-cell sequencing data to investigate the epitope-recognition mechanisms of TCRs. By antigen specificity clustering, we mapped the epitope sequences between epitope-known and epitope-unknown TCRs from COVID-19 patients. One reported SARS-CoV-2 epitope, NQKLIANQF (S919-927), was identified for a TCR expressed by 614 T cells (TCR-614). Epitope screening also identified a potential cross-reactive epitope, KLKTLVATA (NSP31790-1798), for a TCR expressed by 204 T cells (TCR-204). According to the molecular dynamics (MD) simulations, we revealed the detailed epitope-recognition mechanisms for both TCRs. The structural motifs responsible for epitope recognition revealed by the MD simulations are consistent with the sequential features recognized by the sequence-based clustering method. This strategy will facilitate the discovery and optimization of TCR-based therapeutics. In addition, the comprehensive strategy can also promote the development of cancer vaccines in virtue of the ability to discover neoepitopes and epitope-recognition mechanisms.

immunology↗

bioRxiv2023

Telomerase reactivation induces progression of mouse BrafV600E-driven thyroid cancers without telomere lengthening

Mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the paradigm of a cross-cancer alteration in a non-coding region. TERT promoter mutations (TPMs) are biomarkers of poor prognosis in several tumors, including thyroid cancers. TPMs enhance TERT transcription, which is otherwise silenced in adult tissues, thus reactivating a bona fide oncoprotein. To study TERT deregulation and its downstream consequences, we generated a Tert mutant promoter mouse model via CRISPR/Cas9 engineering of the murine equivalent locus (Tert-123C>T) and crossed it with thyroid-specific BrafV600E-mutant mice. We also employed an alternative model of Tert overexpression (K5-Tert). Whereas all BrafV600E animals developed well-differentiated papillary thyroid tumors, 29% and 36% of BrafV600E+Tert-123C>T and BrafV600E+K5-Tert mice progressed to poorly differentiated thyroid cancers at week 20, respectively. Braf+Tert tumors showed increased mitosis and necrosis in areas of solid growth, and older animals from these cohorts displayed anaplastic-like features, i.e., spindle cells and macrophage infiltration. Murine Tert promoter mutation increased Tert transcription in vitro and in vivo, but temporal and intra-tumoral heterogeneity was observed. RNA-sequencing of thyroid tumor cells showed that processes other than the canonical Tert-mediated telomere maintenance role operate in these specimens. Pathway analysis showed that MAPK and PI3K/AKT signaling, as well as processes not previously associated with this tumor etiology, involving cytokine and chemokine signaling, were overactivated. Braf+Tert animals remained responsive to MAPK pathway inhibitors. These models constitute useful pre-clinical tools to understand the cell-autonomous and microenvironment-related consequences of Tert-mediated progression in advanced thyroid cancers and other aggressive tumors carrying TPMs.

cancer biology↗

bioRxiv2023

Characterization and Applications of Evoked Responses During Epidural Electrical Stimulation

Epidural electrical stimulation (EES) of the spinal cord has been FDA approved and used therapeutically for decades. However, there is still not a clear understanding of the local neural substrates and consequently the mechanism of action responsible for the therapeutic effects. Epidural spinal recordings (ESR) are collected from the electrodes placed in the epidural space. ESR contains multi-modality signal components such as the evoked neural response (due to tonic or BurstDR waveforms), evoked muscle response, stimulation artifact, and cardiac response. The tonic stimulation evoked compound action potential (ECAP) is one of the components in ESR and has been proposed recently to measure local neural activation during EES. Here, we first review and investigate the referencing strategies, as they apply to ECAP component in ESR in the domestic swine animal model. We then examine how ECAP component can be used to sense lead migration, an adverse outcome following lead placement that can reduce therapeutic efficacy. Lastly, we show and isolate concurrent activation of local back and leg muscles during EES, demonstrating that the ESR obtained from the recording contacts contain both ECAP and EMG components. These findings may further guide the implementation of recording and reference contacts in an implantable EES system and provide preliminary evidence for the utility of ECAP component in ESR to detect lead migration. We expect these results to facilitate future development of EES methodology and implementation of use of different components in ESR to improve EES therapy.

physiology↗

bioRxiv2023

Dimensional Reduction for Single Molecule Imaging of DNA and Nucleosome Condensation by Polyamines, HP1α and Ki-67

Macromolecules organize themselves into discrete membrane-less compartments. Mounting evidence has suggested that nucleosomes as well as DNA itself can undergo clustering or condensation to regulate genomic activity. Current in vitro condensation studies provide insight into the physical properties of condensates, such as surface tension and diffusion. However, such studies lack the resolution needed for complex kinetic studies of multicomponent condensation. Here, we use a supported lipid bilayer platform in tandem with total internal reflection microscopy to observe the 2-dimensional movement of DNA and nucleosomes at the single-molecule resolution. This dimensional reduction from 3-dimensional studies allows us to observe the initial condensation events and dissolution of these early condensates in the presence of physiological condensing agents. Using polyamines, we observed that the initial condensation happens on a timescale of minutes while dissolution occurs within seconds upon charge inversion. Polyamine valency, DNA length and GC content affect threshold polyamine concentration for condensation. Protein-based nucleosome condensing agents, HP1 and Ki-67, have much lower threshold concentration for condensation than charge-based condensing agents, with Ki-67 being the most effective as low as 100 pM for nucleosome condensation. In addition, we did not observe condensate dissolution even at the highest concentrations of HP1 and Ki-67 tested. We also introduce a two-color imaging scheme where nucleosomes of high density labeled in one color is used to demarcate condensate boundaries and identical nucleosomes of another color at low density can be tracked relative to the boundaries after Ki-67 mediated condensation. Our platform should enable the ultimate resolution of single molecules in condensation dynamics studies of chromatin components under defined physicochemical conditions. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/522433v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1ed0cc9org.highwire.dtl.DTLVardef@1e26b5dorg.highwire.dtl.DTLVardef@1f6e73corg.highwire.dtl.DTLVardef@c7227b_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

The Chromosome-based Genome of Paspalum vaginatum Provides New Insights into Salt-stress Adaptation

Salinization is increasingly a major factor limiting production worldwide. Revealing the mechanism of salt tolerance could help to create salt-tolerant crops and improve their yields. We reported a chromosome-scale genome sequence of the halophyte turfgrass Paspalum vaginatum, and provided structural evidence that it shared a common ancestor with Z. mays and S. bicolor. A total of 107 P. vaginatum germplasms were divided into two groups (China and foreign group) based on the re-sequenced data, and the grouping findings were consistent with the geographical origin. Genome-wide association study (GWAS) of visually scored wilting degree and withering rates identified highly significant QTL on chromosome 6. Combination with RNA-seq, we identified a significantly up-regulated gene under salt stress, which encodes High-affinity K+ Transporter 7 (PvHKT7), as strong candidates underlying the QTL. Overexpression of this gene in Arabidopsis thaliana significantly enhanced salt tolerance by increasing K+ absorption. This study adds new insights into salt-stress adaptation of P. vaginatum and serve as a resource for salt-tolerant improvement of grain crops.

genomics↗

bioRxiv2022

Hedgehogs are the major amplifying hosts of severe fever with thrombocytopenia syndrome virus

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne bandavirus mainly transmitted by Haemaphysalis longicornis in East Asia, mostly in rural areas. To date, the amplifying host involved in the natural transmission of SFTSV remains unidentified. Our epidemiological field survey conducted in endemic areas in China showed that hedgehogs were widely distributed, had heavy tick infestations, and had high SFTSV seroprevalence and RNA prevalence. After experimental infection of Erinaceus amurensis and Atelerix albiventris hedgehogs with SFTSV, robust but transitory viremias were detected, which lasted for around nine to eleven days. The infected hedgehogs experienced light weight loss and histopathology of the spleen showed hemorrhagic necrosis and lymphopenia, with infected hedgehogs recovering after viral clearance. Remarkably, SFTSV transmission cycle between hedgehogs and nymph/adult H. longicornis was easily accomplished under laboratory condition with 100% efficiency. Furthermore, naive H. longicornis ticks could be infected by SFTSV-positive ticks co-feeding on naive hedgehogs, with transstadial transmission of SFTSV also confirmed. We also found that SFTSV viremia remained high in hedgehogs during hibernation, suggesting that this mechanism might contribute to the persistence of SFTSV from one year to the next. Of concern, we recently found evidence of the natural circulation of SFTSV in the urban area of Beijing City in China involving H. longicornis ticks and E. amurensis hedgehogs. Our study suggests that the hedgehogs are the major wildlife amplifying hosts of SFTSV and that urban outbreaks of SFTSV might occur in the future.

microbiology↗