Biology subjects

Ding, W.

Publications and source records attributed to Ding, W..

At least 55 records · Page 3Linked to original sources

bioRxiv2025

Cell-type-specific transposable element demethylation and TAD remodeling in the aging mouse brain

Aging is a major risk factor for neurodegenerative diseases, yet underlying epigenetic mechanisms remain unclear. Here, we generated a comprehensive single-nucleus cell atlas of brain aging across multiple brain regions, comprising 132,551 single-cell methylomes and 72,666 joint chromatin conformation-methylome nuclei. Integration with companion transcriptomic and chromatin accessibility data yielded a cross-modality taxonomy of 36 major cell types. We observed that age-related methylation changes were more pronounced in non-neuronal cells. Transposable element methylation alone distinguished age groups, showing cell-type-specific genome-wide demethylation. Chromatin conformation analysis demonstrated age-related increases in TAD boundary strength with enhanced accessibility at CTCF binding sites. Spatial transcriptomics across 895,296 cells revealed regional heterogeneity during aging within identical cell types. Finally, we developed novel deep-learning models that accurately predict age-related gene expression changes using multi-modal epigenetic features, providing mechanistic insights into gene regulation. This dataset advances our understanding of brain aging and offers potential translational applications. HighlightsO_LISingle-cell multi-omic profiling maps the epigenetic and spatial transcriptomic landscape of brain aging across multiple regions. C_LIO_LICell-type-specific genome-wide demethylation of retrotransposable elements correlates with increased chromatin accessibility and expression. C_LIO_LIElevated TAD boundary strength emerges as a unique marker of brain aging associated with CTCF gaining accessibility. C_LIO_LIA novel deep-learning model reveals the significance of epigenetic features on age-related transcriptomic changes across genes. C_LI

genomics↗

bioRxiv2025

Glial betaPix is essential for blood vessel integrity in the zebrafish brain

The formation of blood-brain barrier and vascular integrity depends on the coordinative development of different cell types in the brain. Previous studies have shown that zebrafish bubblehead (bbh) mutant, which has mutation in the betaPix locus, develops spontaneous intracerebral hemorrhage during early development. However, it remains unclear in which brain cells betaPix may function. Here, we established a highly efficient conditional knockout method in zebrafish by using homology-directed repair (HDR)-mediated knockin and knockout technology, and generated betaPix conditional trap (betaPixct) allele in zebrafish. We found that betaPix in glia, but neither neurons, endothelial cells, nor pericytes, was critical for glial and vascular development and integrity, thus contributing to the formation of blood-brain barrier. Single-cell transcriptome profiling revealed that microtubule aggregation signaling stathmins and pro-angiogenic transcription factors Zfhx3/4 were down-regulated in glial and neuronal progenitors, and further genetic analysis suggested that betaPix may act upstream on the PAK1-Stathmin and Zfhx3/4-Vegfaa signaling to regulate glia migration and angiogenesis. Therefore, this work reveals that glial betaPix plays an important role in brain vascular development in zebrafish embryos and possibly human cells.

developmental biology↗

bioRxiv2025

β-Arrestin Condensates Regulate G Protein-Coupled Receptor Function

G protein-coupled receptors (GPCRs) are the largest class of receptors in the genome and control many signaling cascades essential for survival. GPCR signaling is regulated by {beta}-arrestins, multifunctional adapter proteins that direct receptor desensitization, internalization, and signaling. While at many GPCRs, {beta}-arrestins interact with a wide array of signaling effectors, it is unclear how {beta}-arrestins promote such varied functions. Here we show that {beta}-arrestins undergo liquid-liquid phase separation (LLPS) to form condensates that regulate GPCR function. We demonstrate that {beta}-arrestin oligomerization occurs in proximity to the GPCR and regulates GPCR functions such as internalization and signaling. This model is supported by a cryoEM structure of the adhesion receptor ADGRE1 in a 2:2 complex with {beta}-arrestin 1, with a {beta}-arrestin orientation that can promote oligomerization. Our work provides a paradigm for {beta}-arrestin condensates as regulators of GPCR function, with LLPS serving as an important promoter of signaling compartmentalization at GPCRs.

cell biology↗

bioRxiv2025

Multi-view gene panel characterization for spatially resolved omics

Spatially resolved transcriptomics has transformed our ability to study complex tissues at the cellular and subcellular resolution. However, targeted spatial technologies require pre-selected gene panels, which are typically curated based on existing biological knowledge and prior research hypotheses. While current methods often prioritize capturing cell type information, we argue that an effective gene panel should also capture cell type diversity, cell states, pathway-level information, and minimize redundancy. To address these broader requirements, we developed a gene panel characterization platform that characterizes panels across multiple perspectives, thus allowing us to compare panels comprehensively. Notably, computationally constructed gene panels performed competitively in capturing major cell types when compared to our in-house manually curated panel. However, refined manual curation offered distinct advantages, particularly in capturing minor and rare cell types and exhibited lower information redundancy comparatively. Building on this framework, we integrated these metrics into a deep learning platform, panelScope, leveraging them as a loss function to design holistic gene panels. Using an acute myeloid leukemia (AML) dataset with 42 well-defined cell types and the 5K Xenium panel from 10X Genomics, we demonstrate the utility of our framework in comprehensively characterizing gene panels, enabling the design of tailored panels that address diverse research needs.

bioinformatics↗

bioRxiv2025

Reusing wasted bioresources for crop protection: Calcinated oyster shell powder enhances rhizospheric microbial-mediated suppression of root-knot nematodes

The root-knot nematode (RKN) Meloidogyne incognita is one of the most destructive plant-parasitic nematodes (PPNs) affecting crop production worldwide. Our earlier study revealed that calcinated oyster shell powder (OSP) effectively suppressed tobacco RKN disease. However, the suppression mechanism of OSP against RKNs remain unknown. Our study revealed that calcinated OSP reduced the tobacco root-knot index by more than 38% by inhibiting the migration of second-stage juveniles of Meloidogyne incognita (J2) in the soil. Furthermore, OSP reduced the J2 density in the tobacco rhizosphere by 43.69% and significantly increased the soil pH by 0.68; moreover, OSP increased the contents of soil exchangeable calcium (ExchCa) and exchangeable magnesium (ExchMg) by more than 50%. Moreover, soil properties, including ExchMg, ExchCa and pH, enhanced the microbial-mediated suppression of J2. Specifically, Proteobacteria and Gemmatimonadota dominated the microbial community suppressing RKN, and fungal richness contributed to the suppression of RKNs; in addition, Chloroflexi and Acidobacteria dominated the microbial community promoting RKN prosperity. Our study revealed that the reuse of wasted oyster shell powder as an innovative antagonist is a promising avenue for ecofriendly RKN management strategies. IMPORTANCEThere is increased demand for ecofriendly RKN management strategies, and this study is the first to propose that the reuse of wasted oyster shell powder as an innovative antagonist against RKNs is effective, and calcinated oyster shell powder can reduce tobacco root-knot index and Meloidogyne incognita (J2) density by inhibiting the migration of J2s and enhancing the microbially mediated suppression of J2s in the tobacco rhizosphere. Moreover, several soil microbial and physicochemical indicators, including the contents of soil exchangeable calcium, exchangeable magnesium, pH and the relative abundance of Proteobacteria, Gemmatimonadota, Chloroflexi and Acidobacteria in plant rhizosphere were suggested to guide the development of ecofriendly PPN management strategies.

microbiology↗

bioRxiv2024

Transient glycan-shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques

Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 CD4-binding site (CD4bs) occur infrequently in macaques and humans and have not been reproducibly elicited in any outbred animal model. To address this challenge, we first isolated RHA10, an infection-induced rhesus bNAb with 51% breadth. The cryo-EM structure of RHA10 with HIV-1 envelope (Env) resembled prototypic human CD4bs bNAbs with CDR-H3-dominated binding. Env-antibody co-evolution revealed transient elimination of two Env CD4bs-proximal glycans near the time of RHA10-lineage initiation, and these glycan-deficient Envs bound preferentially to early RHA10 intermediates, suggesting glycan deletions in infecting SHIVs could consistently induce CD4bs bNAbs. To test this, we constructed SHIV.CH505.D3 with CD4bs-proximal glycan deletions. Infection of 10 macaques resulted in accelerated CD4bs bNAb responses in 8, compared with 1 of 115 control macaques. Glycan hole-based immunofocusing coupled to Env-Ab co-evolution can consistently induce broad CD4bs responses in macaques and thus serve as a model for HIV vaccine design. HighlightsO_LIOut of 115 wildtype HIV-1 Env bearing SHIV infected macaques, only one macaque (T681) developed CD4bs bNAbs C_LIO_LICD4bs bNAbs in macaque T681 recognized Env similarly to previously described CDR-H3 dominated human CD4bs bNAbs and exhibited comparable breadth and potency C_LIO_LITransient CD4bs-proximal glycan deletions in macaque T681 preceded bNAb induction C_LIO_LIA novel SHIV with CD4bs-proximal glycan holes and enhanced CD4bs antigenicity immunofocused B cell responses to the CD4bs and elicited cross-clade neutralizing responses in 80% of macaques C_LI

microbiology↗

bioRxiv2024

Representation Learning of Human Disease Mechanisms for a Foundation Model in Rare and Common Diseases

A fundamental challenge in translational medicine is the computational modeling of complex human diseases to accelerate therapeutic development. Representation learning provides a powerful framework to address this, yet creating models that capture deep biological mechanisms remains a critical need. To this end, we propose a novel strategy that partitions the disease landscape into rare and non-rare categories, enabling systematic knowledge repurposing both within and between these groups. Here, we introduce Dis2Vec (Disease to Vector), a representation learning framework designed to operationalize this concept. Dis2Vec generates biologically grounded disease embeddings by learning from human genetic and phenotypic data, forming the foundation for Disease-Disease Association Learning (DDAL) and unsupervised disease clustering. We evaluate Dis2Vec representations in two downstream applications. First, we assess DDAL performance on a transfer learning benchmark designed to predict therapeutic transferability, using real-world drug repurposing investment decisions made in clinical trials. Second, unsupervised clustering analyses reveal shared biological mechanisms across diseases. By modeling the disease landscape in this way, Dis2Vec enhances translational research efficiency across both rare and non-rare diseases, advancing the development of foundational models for therapeutic science. Furthermore, Dis2Vec establishes a biologically grounded disease-representation and benchmarking layer that paves the way for trustworthy agentic biomedical AI systems in rare-disease indication expansion.

systems biology↗

bioRxiv2024

Neutralizing antibodies elicited in sequentially immunized macaques recognize V3 residues on altered conformations of HIV-1 Env trimer

Eliciting broadly neutralizing antibodies that protect against diverse HIV-1 strains is a primary goal of AIDS vaccine research. We characterized Ab1456 and Ab1271, two heterologously-neutralizing antibodies elicited in non-human primates by priming with an engineered V3-targeting SOSIP Env immunogen and boosting with increasingly native-like SOSIP Envs derived from different strain backgrounds. Structures of Env trimers in complex with these antibodies revealed V3 targeting, but on conformational states of Env distinct from the typical closed, prefusion trimeric SOSIP structure. Env trimers bound by Ab1456 adopted conformations resembling CD4-bound open Env states in the absence of soluble CD4, whereas trimers bound by Ab1271 exhibited a trimer apex-altered conformation to accommodate antibody binding. The finding that elicited antibodies cross-neutralized by targeting altered, non-closed, prefusion Env trimer conformations provides important information about Env dynamics that is relevant for HIV-1 vaccine design aimed at raising antibodies to desired epitopes on closed pre-fusion Env trimers. Highlights- Sequential immunization regimen elicits V3 antibodies targeting non-closed Envs - Cryo-EM structures reveal recognition of multiple Env conformational states - Neutralization by elicited antibody does not require antibody-virus preincubation Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/605918v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@6210b1org.highwire.dtl.DTLVardef@35f683org.highwire.dtl.DTLVardef@cb2d3corg.highwire.dtl.DTLVardef@106e066_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Alleviation of salt stress in strawberries by hydrogen-rich water: physiological, transcriptomic and metabolomic responses

O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/605184v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1aa6488org.highwire.dtl.DTLVardef@1ae580borg.highwire.dtl.DTLVardef@11656bcorg.highwire.dtl.DTLVardef@1985c7b_HPS_FORMAT_FIGEXP M_FIG C_FIG With the continuous advancement of climate change and human activities, cultivable land is becoming increasingly susceptible to the influence of salt ions. Therefore, it is crucial to mitigate the salt stress on plants through various approaches. In this study, strawberry seedlings were selected as the experimental plants, and a comprehensive transcriptomic and metabolomic analysis was conducted to elucidate the effects of hydrogen-rich water (HRW) on strawberries under salt stress. The results indicated that HRW significantly promoted plant growth, particularly increasing root biomass by 49.50%. Additionally, HRW regulated the levels of soluble sugars, malondialdehyde (MDA), and antioxidant enzymes, enhancing the cellular uptake of potassium ions and the expulsion of sodium ions. The levels of Ca2+ and Mg2+ in organelles increased by 2.06 and 2.45-fold, respectively. Transcriptomic analysis revealed that HRW substantially altered gene expression in strawberry roots; under salt stress, HRW up-regulated beneficial biological processes. Furthermore, genes related to ion absorption and transport, antioxidant enzymes, and cell wall biosynthesis were screened. Meanwhile, key common pathways were identified in differentially expressed metabolites (DEMs) and differentially expressed genes (DEGs) related to phenylpropane biosynthesis, alanine, aspartate, and glutamate metabolism, amino and nucleotide sugar metabolism, and galactose metabolism. A molecular mechanism for mitigating salt stress in strawberry seedlings by HRW was provided by the integrated approaches in this research, reflecting the potential applications of hydrogen gas in agriculture.

physiology↗

bioRxiv2024

A Message Passing Framework for Precise Cell State Identification with scClassify2

In single-cell analysis, the ability to accurately annotate cells is crucial for downstream exploration. To date, a wide range of approaches have been developed for cell annotation, spanning from classic statistical models to the latest large language models. However, most of the current methods focus on annotating distinct cell types and overlook the identification of sequential cell populations such as transitioning cells. Here, we propose a message-passing-neural-network-based cell annotation method, scClassify2, to specifically focus on adjacent cell state identification. By incorporating prior biological knowledge through a novel dual-layer architecture and employing ordinal regression and conditional training to differentiate adjacent cell states, scClassify2 achieves superior performance compared to other state-of-the-art methods. In addition to single-cell RNA-sequencing data, scClassify2 is generalizable to annotation from different platforms including subcellular spatial transcriptomics data. To facilitate ease of use, we provide a web server hosting over 30 human tissues.

bioinformatics↗

bioRxiv2024

Topology-Driven Negative Sampling Enhances Generalizability in Protein-Protein Interaction Prediction

Unraveling the human interactome to uncover disease-specific patterns and discover drug targets hinges on accurate protein-protein interaction (PPI) predictions. However, challenges persist in machine learning (ML) models due to a scarcity of quality hard negative samples, shortcut learning, and limited generalizability to novel proteins. Here, we introduce a novel approach for strategic sampling of protein-protein non-interactions (PPNIs) by leveraging higher-order network characteristics that capture the inherent complementarity-driven mechanisms of PPIs. Next, we introduce UPNA-PPI (Unsupervised Pre-training of Node Attributes tuned for PPI), a high throughput sequence-to-function ML pipeline, integrating unsupervised pretraining in protein representation learning with topological PPNI samples, capable of efficiently screening billions of interactions. UPNA-PPI improves PPI prediction generalizability and interpretability, particularly in identifying potential binding sites locations on amino acid sequences, strengthening the prioritization of screening assays and facilitating the transferability of ML predictions across protein families and homodimers. UPNA-PPI establishes the foundation for a fundamental negative sampling methodology in graph machine learning by integrating insights from network topology.

bioinformatics↗

bioRxiv2024

Mucin MUC5B levels are reduced in the colonic epithelia of ulcerative colitis patients

Background & AimsUlcerative colitis (UC) is an inflammatory bowel disease (IBD) where a defect in the colonic epithelial barrier elicits a chronic and unresolved inflammatory response against luminal microbiota. Mucins are heavily glycosylated proteins secreted by goblet cells that form gelatinous layers to protect the colonic epithelium. Whereas the role of the major colonic mucin, MUC2, is established in UC, few reports have analyzed MUC5B in this disease. In this study, we investigated MUC5B expression in colonic tissues and organoid cultures from UC patients and non-IBD controls. MethodsMUC5B transcripts were analyzed in colonic regions from UC patients and controls using RT-qPCR. MUC5B protein levels in colonic tissues were analyzed and quantified by immunohistochemistry. Patient-derived epithelial organoids were stained for MUC5B, E-cadherin and F-actin. Organoids were treated with interleukin 1 beta (IL-1{beta}) and MUC5B transcripts were analyzed by RT-qPCR. MUC5B proteins were assessed in IL-1{beta}-treated organoids by immunofluorescent microscopy. ResultsMUC5B transcripts and proteins were expressed in the healthy colon and their levels were decreased in UC tissues. MUC5B proteins were reduced in organoids derived from UC tissues. IL-1{beta} treatment of control organoids stimulated expression of acidic mucins, MUC5B transcripts and MUC5B proteins. MUC5B transcripts were not induced by IL-1{beta} in UC-derived organoids. ConclusionsMUC5B levels are reduced in UC colons and its expression is induced by the IL-1{beta} pro-inflammatory cytokine. These results suggest that MUC5B contributes to the protective colonic mucin layer and that this function is likely compromised in UC.

cell biology↗

bioRxiv2023

Spatially resolved molecular and cellular atlas of the mouse brain

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain.

neuroscience↗

bioRxiv2023

Expression of Filaments of the Geobacter Extracellular Cytochrome OmcS in Shewanella oneidensis

The physiological role of Geobacter sulfurreducens extracellular cytochrome filaments is a matter of debate and the development of proposed electronic device applications of cytochrome filaments awaits methods for large-scale cytochrome nanowire production. Functional studies in Geobacter sulfurreducens are stymied by the broad diversity of redox-active proteins on the outer cell surface and the redundancy and plasticity of extracellular electron transport routes. G. sulfurreducens is a poor chassis for producing cytochrome nanowires for electronics because of its slow, anaerobic growth. Here we report that filaments of the G. sulfurreducens cytochrome OmcS can be heterologously expressed in Shewanella oneidensis. Multiple lines of evidence demonstrated that a strain of S. oneidensis, expressing the G. sulfurreducens OmcS gene on a plasmid, localized OmcS on the outer cell surface. Atomic force microscopy revealed filaments with the unique morphology of OmcS filaments emanating from cells. Electron transfer to OmcS appeared to require a functional outer-membrane porin-cytochrome conduit. The results suggest that S. oneidensis, which grows rapidly to high culture densities under aerobic conditions, may be a suitable for development of a chassis for producing cytochrome nanowires for electronics applications and may also be good model microbe for elucidating cytochrome filament function in anaerobic extracellular electron transfer.

synthetic biology↗

bioRxiv2023

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides a new aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O6mG (the most toxic TMZ-induced lesion), and error-prone bypass of other TMZ-induced lesions. Our analyses of recurrent GBM patient samples establishes a correlation between low RAD18 expression and hypermutation. Taken together we define novel molecular underpinnings for the hallmark tumorigenic phenotypes of TMZ-treated GBM.

cancer biology↗

bioRxiv2023

Adaptive Functions of Structural Variants in Human Brain Development

Quantifying the structural variants (SVs) in nonhuman primates could provide a niche to clarify the genetic backgrounds underlying human-specific traits, but such resource is largely lacking. Here, we report an accurate SV atlas in a population of 562 rhesus macaques, verified by two public SV benchmarks, an inhouse benchmark of eight macaque genomes with long-read sequencing and another inhouse benchmark of one macaque genome with whole-genome assembly. This accurate, quantitative SV map indicates stronger purifying selection on inversions, one type of poorly-clarified SVs to date, especially for those located on regulatory regions, suggesting a strategy for prioritizing inversions with the most important functions. Based on the distribution and the evolutionary features of these inversions in macaque population, we then identified 75 human-specific inversions, clarified their functional effects and prioritized them. Notably, the top-ranked inversions have substantially shaped the human transcriptome, through their dual-effects of reconfiguring the ancestral genomic architecture and introducing regional mutation hotspots at the inverted regions. As a proof-of-concept, we linked APCDD1, located on one of these inversions with the highest rank score and downregulated in human brains, to neuronal maturation. The accumulation of human-specific mutations on its promoter region, accelerated by the formation of the inversion, contributed to the decreased expression in humans. Notably, the overexpression of APCDD1 could accelerate the neuronal maturation, while its depletion in mice delays the neuronal maturation. This study thus highlights the contribution of SVs, especially the inversions, to the distinct features in human brain development.

evolutionary biology↗

bioRxiv2023

BAllC and BAllCools: Efficient Formatting and Operating for Single-Cell DNA Methylation Data

MotivationWith single-cell DNA methylation studies yielding vast datasets, existing data formats struggle with the unique challenges of storage and efficient operations, highlighting a need for improved solutions. ResultsBAllC (Binary All Cytosines) emerges as a tailored binary format for methylation data, addressing these challenges. BAllCools, its complementary software toolkit, enhances parsing, indexing, and querying capabilities, promising superior operational speeds and reduced storage needs. Availabilityhttps://github.com/jksr/ballcools Contactecker@salk.edu Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2023

Germline-targeting chimpanzee SIV Envelopes induce V2-apex broadly neutralizing-like B cell precursors in a rhesus macaque infection model

Eliciting broadly neutralizing antibodies-(bnAbs) remains a major goal of HIV-1 vaccine research. Previously, we showed that a soluble chimpanzee SIV Envelope-(Env) trimer, MT145K, bound several human V2-apex bnAb-precursors and stimulated an appropriate response in V2-apex bnAb precursor-expressing knock-in mice. Here, we tested the immunogenicity of three MT145 variants (MT145, MT145K, MT145K.dV5) expressed as chimeric simian-chimpanzee-immunodeficiency-viruses-(SCIVs) in rhesus macaques-(RMs). All three viruses established productive infections with high setpoint vRNA titers. RMs infected with the germline-targeting SCIV_MT145K and SCIV_MT145K.dV5 exhibited larger and more clonally expanded B cell lineages featuring long anionic heavy chain complementary-determining-regions-(HCDR3s) compared with wildtype SCIV_MT145. Moreover, antigen-specific B cell analysis revealed enrichment for long-CDHR3-bearing antibodies in SCIV_MT145K.dV5 infected animals with paratope features resembling prototypic V2-apex bnAbs and their precursors. Although none of the animals developed bnAbs, these results show that germline-targeting SCIVs can activate and preferentially expand B cells expressing V2-apex bnAb-like precursors, the first step in bnAb elicitation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=180 HEIGHT=200 SRC="FIGDIR/small/558743v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@17673c8org.highwire.dtl.DTLVardef@1ab61a8org.highwire.dtl.DTLVardef@98781forg.highwire.dtl.DTLVardef@1f63e9b_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗