Medicine and Health Sciences Commons^™

Drug Specificity And Affinity Are Encoded In The Probability Of Cryptic Pocket Opening In Myosin Motor Domains, Artur Meller, Jeffrey M Lotthammer, Louis G Smith, Borna Novak, Lindsey A Lee, Catherine C Kuhn, Lina Greenberg, Leslie A Leinwand, Michael J Greenberg, Gregory R Bowman

2020-Current year OA Pubs

The design of compounds that can discriminate between closely related target proteins remains a central challenge in drug discovery. Specific therapeutics targeting the highly conserved myosin motor family are urgently needed as mutations in at least six of its members cause numerous diseases. Allosteric modulators, like the myosin-II inhibitor blebbistatin, are a promising means to achieve specificity. However, it remains unclear why blebbistatin inhibits myosin-II motors with different potencies given that it binds at a highly conserved pocket that is always closed in blebbistatin-free experimental structures. We hypothesized that the probability of pocket opening is an important determinant of the …

Cross Center Single-Cell Rna Sequencing Study Of The Immune Microenvironment In Rapid Progressing Multiple Myeloma, William Pilcher, Reyka G Jayasinghe, Lijun Yao, Mark Fiala, Ravi Vij, Li Ding, Et Al.

2020-Current year OA Pubs

Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM's progression is facilitated by complex interactions with the surrounding bone marrow (BM) cells, forming a microenvironment that supports tumor growth and drug resistance. Understanding the immune microenvironment is key to identifying factors that promote rapid progression of MM. To accomplish this, we performed a multi-center single-cell RNA sequencing (scRNA-seq) study on 102,207 cells from 48 CD138

A Broad Characterization Of Glycogen Storage Disease Iv Patients: A Clinical, Genetic, And Histopathological Study, Matheus Vernet Machado Bressan Wilke, Bibiana Mello De Oliveira, Rodrigo Tzovenos Starosta, Marwan Shinawi, Liang Lu, Mai He, Yamin Ma, Janis Stoll, Carolina Fischinger Moura De Souza, Ana Cecilia Menezes De Siqueira, Sandra Maria Gonçalves Vieira, Carlos Thadeu Cerski, Lilia Farret Refosco, Ida Vanessa Doederlein Schwartz

2020-Current year OA Pubs

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disease caused by variants in the

Gut Microbiota And Microbiota-Derived Metabolites Promotes Endometriosis, Sangappa B Chadchan, Sumanta K Naik, Pooja Popli, Chandni Talwar, Satwikreddy Putluri, Chandrasekhar R Ambati, Michael A Lint, Andrew L Kau, Christina L Stallings, Ramakrishna Kommagani

2020-Current year OA Pubs

Endometriosis is a pathological condition of the female reproductive tract characterized by the existence of endometrium-like tissue at ectopic sites, affecting 10% of women between the age 15 and 49 in the USA. However, currently there is no reliable non-invasive method to detect the presence of endometriosis without surgery and many women find hormonal therapy and surgery as ineffective in avoiding the recurrences. There is a lack of knowledge on the etiology and the factors that contribute to the development of endometriosis. A growing body of recent evidence suggests an association between gut microbiota and endometriosis pathophysiology. However, the direct …

Enhanced Vwf Clearance In Low Vwf Pathogenesis: Limitations Of The Vwfpp/Vwf:Ag Ratio And Clinical Significance, Dearbhla Doherty, Michelle Lavin, Mary Byrne, Margaret Nolan, Jamie M O'Sullivan, Kevin Ryan, Niamh M O'Connell, Sandra L Haberichter, Pamela A Christopherson, Jorge Di Paola, Paula D James, James S O'Donnell

2020-Current year OA Pubs

Increased von Willebrand factor (VWF) clearance plays a key role in the pathogenesis of type 1 and type 2 von Willebrand disease (VWD). However, the pathological mechanisms involved in patients with mild to moderate reductions in plasma VWF:Ag (range, 30-50 IU/dL; low VWF) remain poorly understood. In this study, we investigated the hypothesis that enhanced VWF clearance may contribute to the pathobiology of low VWF. Patients with low VWF were recruited to the LoVIC study after ethics approval and receipt of informed consent. Desmopressin was administered IV in 75 patients, and blood samples were drawn at baseline and at the …

Quantification Of Localized Nad+ Changes Reveals Unique Specificity Of Nad+ Regulation In The Hypothalamus, Sean Johnson, Kiyoshi Yoshioka, Cynthia S Brace, Shin-Ichiro Imai

2020-Current year OA Pubs

Recently, it has become a consensus that systemic decreases in NAD

Structure-Function Correlates Of Fibrinogen Binding By Acinetobacter Adhesins Critical In Catheter-Associated Urinary Tract Infections, Kevin O Tamadonfar, Gisela Di Venanzio, Jerome S Pinkner, Karen W Dodson, Vasilios Kalas, Maxwell I Zimmerman, Jesus Bazan Villicana, Gregory R Bowman, Mario F Feldman, Scott J Hultgren

2020-Current year OA Pubs

Multidrug-resistant

A Selective Inhibitor Of The Sperm-Specific Potassium Channel Slo3 Impairs Human Sperm Function, Maximilian Lyon, Ping Li, Juan J Ferreira, Aluet Borrego Alvarez, Lis C Puga Molina, Pascale Lybaert, Saayli Khambekar, Alicia Liu, Celia M Santi, Et Al.

2020-Current year OA Pubs

To fertilize an oocyte, the membrane potential of both mouse and human sperm must hyperpolarize (become more negative inside). Determining the molecular mechanisms underlying this hyperpolarization is vital for developing new contraceptive methods and detecting causes of idiopathic male infertility. In mouse sperm, hyperpolarization is caused by activation of the sperm-specific potassium (K

E. Coli Catheter-Associated Urinary Tract Infections Are Associated With Distinctive Virulence And Biofilm Gene Determinants, Zongsen Zou, Robert F. Potter, William H. Mccoy, John A. Wildenthal, George L. Katumba, Peter J. Mucha, Gautam Dantas, Jeffrey P. Henderson

2020-Current year OA Pubs

Urinary catheterization facilitates urinary tract colonization by E. coli and increases infection risk. Here, we aimed to identify strain-specific characteristics associated with the transition from colonization to infection in catheterized patients. In a single-site study population, we compared E. coli isolates from patients with catheter-associated asymptomatic bacteriuria (CAASB) to those with catheter-associated urinary tract infection (CAUTI). CAUTI isolates were dominated by a phylotype B2 subclade containing the multidrug-resistant ST131 lineage relative to CAASB isolates, which were phylogenetically more diverse. A distinctive combination of virulence-associated genes was present in the CAUTI-associated B2 subclade. Catheter-associated biofilm formation was widespread among isolates and …

Comparison Of State-Of-The-Art Neural Network Survival Models With The Pooled Cohort Equations For Cardiovascular Disease Risk Prediction, Yu Deng, Lei Liu, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Pooled Cohort Equations (PCEs) are race- and sex-specific Cox proportional hazards (PH)-based models used for 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction with acceptable discrimination. In recent years, neural network models have gained increasing popularity with their success in image recognition and text classification. Various survival neural network models have been proposed by combining survival analysis and neural network architecture to take advantage of the strengths from both. However, the performance of these survival neural network models compared to each other and to PCEs in ASCVD prediction is unknown.

METHODS: In this study, we used 6 cohorts from …

Osteoclasts, Master Sculptors Of Bone, Deborah J Veis, Charles A O'Brien

2020-Current year OA Pubs

Osteoclasts are multinucleated cells with the unique ability to resorb bone matrix. Excessive production or activation of osteoclasts leads to skeletal pathologies that affect a significant portion of the population. Although therapies that effectively target osteoclasts have been developed, they are associated with sometimes severe side effects, and a fuller understanding of osteoclast biology may lead to more specific treatments. Along those lines, a rich body of work has defined essential signaling pathways required for osteoclast formation, function, and survival. Nonetheless, recent studies have cast new light on long-held views regarding the origin of these cells during development and homeostasis, …

Evaluation Of Raavrh74 Gene Therapy Vector Seroprevalence By Measurement Of Total Binding Antibodies In Patients With Duchenne Muscular Dystrophy, Natalie L Goedeker, Sachi D Dharia, Danielle A Griffin, Jesantha Coy, Todd Truesdale, Rajan Parikh, Kasen Whitehouse, Sourav Santra, Damon R Asher, Craig M Zaidman

2020-Current year OA Pubs

BACKGROUND: Adeno-associated virus (AAV) vectors are a promising platform for

OBJECTIVE: To evaluate prevalence of total binding antibodies (neutralizing and non-neutralizing) against rAAVrh74 in patients with DMD.

METHODS: Eligible individuals (

RESULTS: A large preponderance (86.1%) of patients with DMD in this data set was seronegative for anti-rAAVrh74 total binding antibodies. These patients would potentially meet the antibody status eligibility criterion for entry into rAAVrh74-based gene therapy clinical trials.

CONCLUSION: Measuring total binding antibodies is a more comprehensive approach to assess pre-existing immune response

Distinct Clonal Identities Of B-Alls Arising After Lenolidomide Therapy For Multiple Myeloma, Erica K Barnell, Zachary L Skidmore, Kenneth F Newcomer, Monique Chavez, Katie M Campbell, Kelsy C Cotto, Nicholas C Spies, Marianna B Ruzinova, Tianjiao Wang, Brooj Abro, Bijal A Parikh, Eric J Duncavage, John L Frater, Yi-Shan Lee, Anjum Hassan, Justin A King, Daniel R Kohnen, Mark A Fiala, John S Welch, Geoffrey L Uy, Kiran Vij, Ravi Vij, Malachi Griffith, Obi L Griffith, Lukas D Wartman, Et Al.

2020-Current year OA Pubs

Patients with multiple myeloma (MM) who are treated with lenalidomide rarely develop a secondary B-cell acute lymphoblastic leukemia (B-ALL). The clonal and biological relationship between these sequential malignancies is not yet clear. We identified 17 patients with MM treated with lenalidomide, who subsequently developed B-ALL. Patient samples were evaluated through sequencing, cytogenetics/fluorescence in situ hybridization (FISH), immunohistochemical (IHC) staining, and immunoglobulin heavy chain (IgH) clonality assessment. Samples were assessed for shared mutations and recurrently mutated genes. Through whole exome sequencing and cytogenetics/FISH analysis of 7 paired samples (MM vs matched B-ALL), no mutational overlap between samples was observed. Unique dominant …

Clinical Outcomes In Patients Relapsed/Refractory After ≥2 Prior Lines Of Therapy For Follicular Lymphoma: A Systematic Literature Review And Meta-Analysis, Steve Kanters, Graeme Ball, Brad Kahl, Adriana Wiesinger, Eve H Limbrick-Oldfield, Akshay Sudhindra, Julia Thornton Snider, Anik R Patel

2020-Current year OA Pubs

BACKGROUND: Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapy (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT identified through systematic literature review.

METHODS: Eligible studies included comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT published prior to 31st May 2021. Prior LOT must have included an anti-CD20 monoclonal antibody and an …

Lateral Line Ablation By Ototoxic Compounds Results In Distinct Rheotaxis Profiles In Larval Zebrafish, Kyle C Newton, Dovi Kacev, Simon R O Nilsson, Allison L Saettele, Sam A Golden, Lavinia Sheets

2020-Current year OA Pubs

The zebrafish lateral line is an established model for hair cell organ damage, yet few studies link mechanistic disruptions to changes in biologically relevant behavior. We used larval zebrafish to determine how damage via ototoxic compounds impact rheotaxis. Larvae were treated with CuSO

Treatment Outcomes And Roles Of Transplantation And Maintenance Rituximab In Patients With Previously Untreated Mantle Cell Lymphoma: Results From Large Real-World Cohorts, Peter Martin, Jonathon B Cohen, Michael Wang, Anita Kumar, Brian Hill, Diego Villa, Jeffrey M Switchenko, Brad Kahl, Kami Maddocks, Natalie S Grover, Keqin Qi, Lori Parisi, Katherine Daly, Angeline Zhu, Gilles Salles

2020-Current year OA Pubs

PURPOSE: Commonly used first-line (1L) treatments for mantle cell lymphoma include high-dose cytarabine-based induction followed by autologous stem-cell transplant (ASCT) for younger patients and several chemoimmunotherapy regimens for older patients. Continuous debates exist on the role of ASCT in younger patients and maintenance rituximab (MR) after bendamustine plus rituximab (BR).

METHODS: Retrospective data from 4,216 patients with mantle cell lymphoma in the Flatiron Health electronic record-derived deidentified database diagnosed between 2011 and 2021, mostly in US community oncology settings, were evaluated for treatment patterns and outcomes. The efficacy findings with ASCT and MR were validated in an independent cohort of …

Impact Of The Covid-19 Pandemic On Burnout And Perceived Workplace Quality Among Addiction Treatment Providers, Andrea Fentem, Raven Riordan, Christine Doroshenko, Xiao Li, Erin Kasson, Devin Banks, Rachel P Winograd, Patricia Cavazos-Rehg

2020-Current year OA Pubs

BACKGROUND: This study examines the impact of the COVID-19 pandemic on work satisfaction, work-related stress, and perceived work quality among substance use treatment providers to better understand challenges faced among this group during the pandemic.

METHODS: Participants of this study were 91 addiction treatment providers (e.g., therapists, physicians, community support specialists, administrative staff) recruited from various treatment facilities (e.g., inpatient and outpatient settings). Mixed method analyses were conducted to assess self-reported burnout, sources of work-related stress, and perceived work quality during the pandemic. Responses from providers reporting COVID-19 related decreases in work quality were compared to responses from providers who …

Synthetic Biology Design As A Paradigm Shift Toward Manufacturing Affordable Adeno-Associated Virus Gene Therapies, Logan Thrasher Collins, Selvarangan Ponnazhagan, David T Curiel

2020-Current year OA Pubs

Gene therapy has demonstrated enormous potential for changing how we combat disease. By directly engineering the genetic composition of cells, it provides a broad range of options for improving human health. Adeno-associated viruses (AAVs) represent a leading gene therapy vector and are expected to address a wide range of conditions in the coming decade. Three AAV therapies have already been approved by the FDA to treat Leber's congenital amaurosis, spinal muscular atrophy, and hemophilia B. Yet these therapies cost around $850,000, $2,100,000, and $3,500,000, respectively. Such prices limit the broad applicability of AAV gene therapy and make it inaccessible to …

Personalized Therapeutics For Katp-Dependent Pathologies, Colin G Nichols

2020-Current year OA Pubs

Ubiquitously expressed throughout the body, ATP-sensitive potassium (K

Identifying Biomarkers Of Differential Chemotherapy Response In Tnbc Patient-Derived Xenografts With A Ctd/Wgcna Approach, Varduhi Petrosyan, Shunqiang Li, Et Al.

2020-Current year OA Pubs

Although systemic chemotherapy remains the standard of care for TNBC, even combination chemotherapy is often ineffective. The identification of biomarkers for differential chemotherapy response would allow for the selection of responsive patients, thus maximizing efficacy and minimizing toxicities. Here, we leverage TNBC PDXs to identify biomarkers of response. To demonstrate their ability to function as a preclinical cohort, PDXs were characterized using DNA sequencing, transcriptomics, and proteomics to show consistency with clinical samples. We then developed a network-based approach (CTD/WGCNA) to identify biomarkers of response to carboplatin (MSI1, TMSB15A, ARHGDIB, GGT1, SV2A, SEC14L2, SERPINI1, ADAMTS20, DGKQ) and docetaxel (c, MAGED4, …

A Pleiotropic Chemoreceptor Facilitates The Production And Perception Of Mating Pheromones, Cassondra L Vernier, Nicole Leitner, Kathleen M Zelle, Merrin Foltz, Sophia Dutton, Xitong Liang, Sean Halloran, Jocelyn G Millar, Yehuda Ben-Shahar

2020-Current year OA Pubs

Optimal mating decisions depend on the robust coupling of signal production and perception because independent changes in either could carry a fitness cost. However, since the perception and production of mating signals are often mediated by different tissues and cell types, the mechanisms that drive and maintain their coupling remain unknown for most animal species. Here, we show that in

Semantic Wikis As Flexible Database Interfaces For Biomedical Applications, Marco Falda, Manfredo Atzori, Maurizio Corbetta

2020-Current year OA Pubs

Several challenges prevent extracting knowledge from biomedical resources, including data heterogeneity and the difficulty to obtain and collaborate on data and annotations by medical doctors. Therefore, flexibility in their representation and interconnection is required; it is also essential to be able to interact easily with such data. In recent years, semantic tools have been developed: semantic wikis are collections of wiki pages that can be annotated with properties and so combine flexibility and expressiveness, two desirable aspects when modeling databases, especially in the dynamic biomedical domain. However, semantics and collaborative analysis of biomedical data is still an unsolved challenge. The …

Urine Cell-Free Dna Multi-Omics To Detect Mrd And Predict Survival In Bladder Cancer Patients, Pradeep S Chauhan, Alexander Shiang, Irfan Alahi, Wenjia Feng, Cayce Nawaf, Kevin Chen, Peter K Harris, Faridi Qaium, Casey Hatscher, Anna Antiporda, Lindsey Brunt, Lindsey R Mayer, Brian C Baumann, Eric H Kim, Melissa A Reimers, Zachary L Smith, Aadel A Chaudhuri, Et Al.

2020-Current year OA Pubs

Circulating tumor DNA (ctDNA) sensitivity remains subpar for molecular residual disease (MRD) detection in bladder cancer patients. To remedy this problem, we focused on the biofluid most proximal to the disease, urine, and analyzed urine tumor DNA in 74 localized bladder cancer patients. We integrated ultra-low-pass whole genome sequencing (ULP-WGS) with urine cancer personalized profiling by deep sequencing (uCAPP-Seq) to achieve sensitive MRD detection and predict overall survival. Variant allele frequency, inferred tumor mutational burden, and copy number-derived tumor fraction levels in urine cell-free DNA (cfDNA) significantly predicted pathologic complete response status, far better than plasma ctDNA was able to. …

Virome Analysis And Association Of Positive Coxsackievirus B Serology During Pregnancy With Congenital Heart Disease, Mathieu Garand, Susie S Y Huang, Lisa S Goessling, Fei Wan, Donna A Santillan, Mark K Santillan, Anoop Brar, Todd N Wylie, Kristine M Wylie, Pirooz Eghtesady

2020-Current year OA Pubs

BACKGROUND: We have previously shown coxsackievirus B (CVB) to be a potent inducer of congenital heart disease (CHD) in mice. The clinical relevance of these findings in humans and the roles of other viruses in the pathogenesis of CHD remain unknown.

METHODS: We obtained plasma samples, collected at all trimesters, from 89 subjects (104 pregnancies), 73 healthy controls (88 pregnancies), and 16 with CHD-affected birth (16 pregnancies), from the Perinatal Family Tissue Bank (PFTB). We performed CVB IgG/IgM serological assays on plasma. We also used ViroCap sequencing and PCR to test for viral nucleic acid in plasma, circulating leukocytes from …

Epigenetic Resetting In The Human Germ Line Entails Histone Modification Remodeling, Wolfram H Gruhn, Walfred W C Tang, Sabine Dietmann, João P Alves-Lopes, Christopher A Penfold, Frederick C K Wong, Navin B Ramakrishna, M Azim Surani

2020-Current year OA Pubs

Epigenetic resetting in the mammalian germ line entails acute DNA demethylation, which lays the foundation for gametogenesis, totipotency, and embryonic development. We characterize the epigenome of hypomethylated human primordial germ cells (hPGCs) to reveal mechanisms preventing the widespread derepression of genes and transposable elements (TEs). Along with the loss of DNA methylation, we show that hPGCs exhibit a profound reduction of repressive histone modifications resulting in diminished heterochromatic signatures at most genes and TEs and the acquisition of a neutral or paused epigenetic state without transcriptional activation. Efficient maintenance of a heterochromatic state is limited to a subset of genomic …

Conserved Angio-Immune Subtypes Of The Tumor Microenvironment Predict Response To Immune Checkpoint Blockade Therapy, Madhav Subramanian, Ashraf Ul Kabir, Derek Barisas, Karen Krchma, Kyunghee Choi

2020-Current year OA Pubs

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment. However, only a fraction of patients respond to ICB therapy. Accurate prediction of patients to likely respond to ICB would maximize the efficacy of ICB therapy. The tumor microenvironment (TME) dictates tumor progression and therapy outcome. Here, we classify the TME by analyzing the transcriptome from 11,069 cancer patients based on angiogenesis and T cell activity. We find three distinct angio-immune TME subtypes conserved across 30 non-hematological cancers. There is a clear inverse relationship between angiogenesis and anti-tumor immunity in TME. Remarkably, patients displaying TME with low angiogenesis with strong anti-tumor …

Posoleucel, An Allogeneic, Off-The-Shelf Multivirus-Specific T-Cell Therapy, For The Treatment Of Refractory Viral Infections In The Post-Hct Setting, Thomas Pfeiffer, Et Al.

2020-Current year OA Pubs

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus.

PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either …

Differential Effects Of Anti-Cd20 Therapy On Cd4 And Cd8 T Cells And Implication Of Cd20-Expressing Cd8 T Cells In Ms Disease Activity, Koji Shinoda, Anne H Cross, Et Al.

2020-Current year OA Pubs

A small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology. Peripheral blood mononuclear cells from independent discovery and validation cohorts of MS patients initiating ocrelizumab were assessed for phenotypic and functional profiles using multiparametric flow cytometry. Pretreatment CD20-expressing T cells, especially CD20

Prm-Reactive Antibodies Reveal A Role For Partially Mature Virions In Dengue Virus Pathogenesis, Kimberly A Dowd, Laura A Vanblargan, Rita E Chen, Bradley M Whitener, Jennifer Govero, Soila Sukupolvi-Petty, Michael S Diamond, Et Al.

2020-Current year OA Pubs

Cleavage of the flavivirus premembrane (prM) structural protein during maturation can be inefficient. The contribution of partially mature flavivirus virions that retain uncleaved prM to pathogenesis during primary infection is unknown. To investigate this question, we characterized the functional properties of newly-generated dengue virus (DENV) prM-reactive monoclonal antibodies (mAbs) in vitro and using a mouse model of DENV disease. Anti-prM mAbs neutralized DENV infection in a virion maturation state-dependent manner. Alanine scanning mutagenesis and cryoelectron microscopy of anti-prM mAbs in complex with immature DENV defined two modes of attachment to a single antigenic site. In vivo, passive transfer of intact …

Entry Receptors - The Gateway To Alphavirus Infection, Ofer Zimmerman, Autumn C. Holmes, Natasha M. Kafai, Lucas J. Adams, Michael S. Diamond

2020-Current year OA Pubs

Alphaviruses are enveloped, insect-transmitted, positive-sense RNA viruses that infect humans and other animals and cause a range of clinical manifestations, including arthritis, musculoskeletal disease, meningitis, encephalitis, and death. Over the past four years, aided by CRISPR/Cas9-based genetic screening approaches, intensive research efforts have focused on identifying entry receptors for alphaviruses to better understand the basis for cellular and species tropism. Herein, we review approaches to alphavirus receptor identification and how these were used for discovery. The identification of new receptors advances our understanding of viral pathogenesis, tropism, and evolution and is expected to contribute to the development of novel strategies …