Virus Diseases Commons^™

Heartland Virus Preclinical Research Project, Brian B. Gowen

Funded Research Records

No abstract provided.

Inhibiting Chikungunya Virus Protease Using Mtase-Like Domain Interactions For Novel Antiviral Therapies, Justin G. Julander

Funded Research Records

No abstract provided.

Testing Elicitors Of Homologous Jadr2 Proteins To Regulate Natural Product Production, Carzon J. Williams, Emilee A. Patterson, Allison S. Walker

SPARK Symposium Presentations

The growing threat of antimicrobial resistance (AMR) has and will contribute to global economic and public health concerns in the foreseeable future leading into 2050. As mortality rates derived from AMR are projected to reach 10 million if no viable solution is found to combat it through hastened drug discovery. The use of natural products to mitigate AMRs effects is viable as more than 50% of FDA approved drugs are natural products. These natural products are synthesized by biosynthetic gene clusters (BGC), found in bacteria with a regulatory protein not allowing transcription until unbound . Current methods of eliciting the …

Sirt1 And Ifi16 Cooperatively Regulate Hbv Replication Via Epigenetic Modulation And Innate Immune Activation, Zahra Zahid Piracha, Umar Saeed, Neelam Abid, Syed Shahan Gilani, Hafiz Ahmad Bilal Akhtar Chughtai, Areesha Wasti, Muhammad Waseem, Dilber Uzun Ozsahin, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Background

Hepatitis B virus (HBV) establishes persistent infection through the formation of a covalently closed circular DNA (cccDNA) minichromosome, which enables immune evasion and sustained viral replication. While SIRT1, IFI16, and STING are known to modulate antiviral pathways, their cooperative role in regulating HBV transcription and host immunity remains poorly defined.

Methods

We investigated the functional interplay between SIRT1, IFI16, and STING using confocal microscopy, chromatin immunoprecipitation (ChIP), gene silencing, and quantitative PCR in HBV-replicating cell models. Interactions with HBV cccDNA and effects on viral transcription and interferon-stimulated gene (ISG) expression were analyzed. Northern blotting and RT-qPCR were used to …

Expert Recommendations To Strengthen Chikungunya Outbreak Surveillance And Reporting For Traveler Health Protection, Daniel C. Payne, Karoun H. Bagamian, Jeffery Goad, Nathan D. Grubaugh, Michael A. Johansson, Moritz U. G. Kraemer, Eyal Leshem, Francesca F. Norman, Alfonso J. Rodríguez-Morales, Henrik Salje, Stephen Thomas, Scott C. Weaver, Lindsey A. Laytner, Rebecca Sturgis, Suzanne K. Scheele, Davidson H. Hamer

Pharmacy Faculty Articles and Research

Chikungunya, a debilitating mosquito-borne disease caused by chikungunya virus, has surged dramatically in the past two decades. Chikungunya outbreaks can intensify rapidly, with infections posing a significant endemic health burden in tropical/subtropical areas and for travelers. Health professionals require timely and accurate outbreak information to adequately protect travelers and assess chikungunya risk. However, detection is often insufficient in the areas most susceptible to outbreaks, leading to diagnostic and reporting delays. Consequently, travelers are often unaware of increased chikungunya infection risk at their destination. We assessed chikungunya surveillance and reporting resources, and we developed expert recommendations for traveler health protection. Because …

Sepsis As An Immune Continuum: Cytokine Storm To Lymphopenia And Pics, Chelsey King

Senior Honors Theses

Sepsis is a leading cause of morbidity and mortality worldwide, driven by a dynamic immune continuum that progresses from early hyperinflammation to profound immunosuppression. This review examines the three overlapping phases of sepsis: the inflammation-mediated cytokine storm driven by dysregulated PRR activation, NF-κB signaling, and NETosis; apoptosis-driven lymphopenia involving caspase-mediated lymphocyte death, dendritic cell dysfunction, and metabolic exhaustion; and prolonged immunoparalysis culminating in persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Key mechanisms linking these phases, including the co-existence of hyper- and hypo-inflammatory states, are synthesized alongside relevant clinical biomarkers such as IL-6, HLA-DR, and single-cell immune profiles. This review highlights …

Mechanisms Of Binding And Immune Escape Resistance For Broadly Neutralizing Antibodies Targeting Distinct Conserved Sars-Cov-2 Spike Epitopes: A Hierarchical Approach Integrating Mutational Profiling And Energy Landscape Analysis, Mohammed Alshahrani, Will Gatlin, Max Ludwick, Lucas Turano, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The continued evolution of SARS-CoV-2 has enabled an escape from most monoclonal antibodies, yet a subset of broadly neutralizing antibodies targeting three newly identified super-conserved RBD epitopes—SCORE-A, SCORE-B, and SCORE-C—retains remarkable activity against even the most recent JN.1-derived sublineages. Here, we employed an integrated computational framework combining conformational dynamics, mutational scanning, MM-GBSA binding energetics, and frustration profiling to dissect the molecular mechanisms by which XGI antibodies achieve broad neutralization and resistance to immune escape. Structural analysis revealed that all three SCORE epitopes share a common architecture: a highly conserved, minimally frustrated core that provides stable anchoring, flanked by peripheral regions …

Limited English Proficiency, Acculturative Stress, And Quality Of Life Among Korean American Patients With Chronic Hepatitis B, Hee-Soon Juon, Gilbert C. Gee, Julia G. Katcher, Daniel Yang, Katherine Smith, Ann C. Klassen

Department of Medical Oncology Faculty Papers

BACKGROUND: Chronic hepatitis B (CHB) is one of the most widespread liver diseases in the world and disproportionately affects Asian Americans, who are further impacted by the lower quality of life imposed by the infection. Limited English proficiency (LEP) and acculturative stress play an important role in the study of patients with CHB, but the interrelationships of LEP, acculturative stress, and health outcomes are not well studied in this population. This study aims to explore how acculturative stress mediates the relationship between LEP and health outcomes among Korean American patients with CHB.

METHODS: A total of 365 CHB patients completed …

Beat-Bk: An Adaptive, Randomized Controlled Trial To Treat Polyomavirus Infections (Bkpyv) In Kidney And Kidney-Pancreas Transplantation Recipients (Beat-Bk) Study Protocol, Ryan Gately, Michael Dymock, Dharshana Sabanayagam, Scott B. Campbell, Jonathan C. Craig, Vikas Dharnidharka, Anna Francis, Jonathan M. Gleadle, Martin Hajek, Sana Hamilton, Martin Howell, Nicole Isbel, Allison Jaure, David W. Johnson, John Kanellis, Karen Keung, Siah Kim, Jen Kok, Dirk R. Kuypers, Nicholas Larkins, Wai H. Lim, Rahul Mainra, Julie A. Marsh, Gabor Mihala, Brian Nankivell, Samantha Ng

Research outputs 2022 to 2026

Background. – BK polyomavirus (BKPyV) is a common opportunistic infection in kidney transplant recipients, typically reactivating in the context of immunosuppression. Although asymptomatic in immunocompetent individuals, reactivation in transplant recipients can cause BKPyV-associated nephropathy (BKPyVAN), a leading cause of graft dysfunction and loss. BKPyV viremia affects approximately 10%–15% of transplant recipients, and once BKPyVAN is established, the risk of graft failure can exceed 50%. The current standard of care involves immunosuppression reduction to restore virus-specific immunity, but this approach increases the risk of acute and chronic rejection. Intravenous immunoglobulin (IVIg), which contains antiviral and immunomodulatory antibodies, has been proposed as …

Population Analysis And Immunologic Landscape Of Melanoma In People Living With Hiv, Lindsay Barger, Derek Wang, Ashley Saravia, Valeria Mezzano, Gyles Ward, Cynthia Loomis, Carly Feldman, Madalina Tuluc, Rino Seedor, Peter Gaskill, Anna Coghill, Gita Suneja, Iman Dehzangi, Jennifer Hope, George Jour, Gabriele Romano

Department of Medical Oncology Faculty Papers

PURPOSE: To dissect the clinical and immunologic features of people living with human immunodeficiency virus (HIV; PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer.

EXPERIMENTAL DESIGN: We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n = 11), with downstream validation using multiplex immunofluorescence (mIF; n = 15 PLWH, n = 14 PLw/oH).

RESULTS: PLWH were diagnosed at a younger age, had a greater representation of Hispanic and …

Variation In Antiviral Immunity And Inflammation Pathways Precedes Hiv-1 Infection In A High-Risk African Cohort, Mwikali Kioko, Shaban Mwangi, Lynn Fwambah, Amin Hassan, Jason Blackard, Philip Bejon, Eduard Sanders, Thumbi Ndung’U, Eunice Nduati, Abdirahman Abdi

Institute for Human Development, East Africa

BACKGROUND. Susceptibility to HIV-1 infection varies between individuals, but the biological determinants of acquisition risk remain poorly defined.

METHODS. We conducted a case-control study nested within a high-risk cohort in Kenya. We compared the plasma extracellular RNA collected before HIV-1 acquisition with that from matched uninfected individuals acting as controls to identify immunological processes linked to infection risk.

RESULTS. Individuals who later acquired HIV-1 exhibited upregulation of immune processes that facilitate viral infection, including T cell suppression and type II IFN and Th2 immune responses. In contrast, processes associated with antiviral defence and tissue repair, such as …

Early And Sustained Improvements In Sense Of Smell With Tezepelumab Treatment In Patients With Chronic Rhinosinusitis With Nasal Polyps (Waypoint), Joaquim Mullol, Joseph K. Han, Tanya M. Laidlaw, Claire Hopkins, Anju T. Peters, Oliver Pfaar, Martin Desrosiers, Stella E. Lee, Andrew P. Lane, Claudia Chen, Yun Chon, Sandhia S. Ponnarambil, Andrews Foster, Andrew W. Lindsley, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

Background

Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting health-related quality of life and posing a safety hazard.

Methods

WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22-item Sino-Nasal Outcome Test (SNOT-22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 …

A Painful Diffuse Rash, Bruce M. Lo, Melanie Shoemaker, Kiersten Potter, Katherine Schaffer

Department of Emergency Medicine Faculty Publications

[Patient presentation]

A 41-year-old male with no past medical history presented with 1 week of ulcers to the left side of his face, followed by several days of a painful rash to the trunk and back after a sexual encounter. The patient denies any fever or previous rash and any illicit drug use. Initial vital signs included a temperature of 97 °F, a heart rate of 89 beats per minute, and blood pressure of 135/79 mm Hg. Physical examination revealed a macular papular rash across his trunk and back (Fig 1) and facial ulcerations with eschar (Fig 2) at the …

Proof-Of-Concept Development And Preclinical Evaluation Of A Microarray Patch Platform For Codelivery Of Multiple Broadly Neutralizing Antibodies For Hiv Prevention, M. Melissa Peet, Vivek Agrahari, Parbeen Singh, Lam Luong Hoai Nguyen, Louise A. Ouattara, Eun Sung Yang, Carolina Herrera, Amarendra Pegu, Theodore C. Pierson, Thanh D. Nguyen, Gustavo F. Doncel

CONRAD Publications

Broadly neutralizing antibodies (bnAbs) are advancing as a preventative or treatment option for HIV infection, but currently must be administered parenterally, typically as a large injection or infusion, an invasive method of delivery, especially for the pediatric population. Here, we present proof-of-concept data on a minimally invasive microneedle (MN) patch platform codelivering three bnAbs, PGT121, VRC07-523LS, and PGDM1400LS, from separate MN patch units or pixels. Each 1 cm² patch pixel, fabricated via solvent casting, contained ∼2 mg of one bnAb. In ex vivo porcine skin tests, the MNs effectively penetrated the skin. When tested in vitro in PBS buffer, MNs …

Mortality From Or With Covid-19 Infection, Dagan Coppock, Joseph Glowacki, Constantine Daskalakis, John Zurlo, Nikita Jaggernauth, Daniel Taupin

Division of Infectious Diseases and Environmental Medicine Faculty Papers

In this retrospective study, we compared the cause of death among hospitalized patients who died with a diagnosis of COVID-19 across two periods of the pandemic two years apart: an early period (admissions June to October 2020), when the population was immunologically naïve, and a later period (admissions April to October 2022), when an estimated 96% of the population had immunity from prior infection, vaccination, or both. Two investigators independently reviewed the medical records of 100 in-hospital deaths (50 per period) and classified each death as COVID-19 related, uncertain, or not COVID-19 related, using logistic regression to compare the two …

Modulation Of Prussian Blue Redox Signaling By Molecular Imprinting For Reagent-Free Electrochemical Detection Of Emtricitabine, Abdellatif Ait Lahcen, Gymama Slaughter

Center for Bioelectronics Publications

Reagent-free electrochemical sensors offer significant benefits for rapid, affordable point-of-care drug testing. In this study, we introduce a novel, reagent-free electrochemical sensor based on a molecularly imprinted polymer (MIP) specifically designed for the selective detection of Emtricitabine (FTC), a common antiretroviral used in HIV therapy. The sensor uses laser-induced graphene (LIG) electrodes, renowned for their high conductivity and porosity, ideal for electrochemical sensing. To enable reagent-free operation, the LIG surface was electrochemically coated with Prussian Blue, serving as a redox-active layer. Next, an MIP-PPy film was electropolymerized onto the Prussian Blue surface in the presence of FTC as a template, …

Prevalence Of Dengue Infection In Bangladesh: A Systematic Review And Meta-Analysis, Md. Estiar Rahman, Abdullah Al-Taiar, May Salama, Michele A. Kekeh, Ahmed N. Albatineh

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Objective: 

To estimate the pooled prevalence of dengue infection in Bangladesh.

Methods:

Literature search was conducted across PubMed, Web of Science, and Hinari between December 2024 and April 2025, supplemented by references searching. The Joanna Briggs Institute checklist was used for evaluating study quality. A random effects meta-analysis of proportion, including subgroup analyses, was performed with R software (version 4.5.1).

Results:

Out of 2 087 records, 28 studies were included. The pooled prevalence of confirmed dengue infection among clinically suspected patients was 49.3% (95% Cl 36.1-62.6), with a significant high heterogeneity (I²=99.2%, τ²=1.81, P< 0.001). Stratified analysis showed a pooled prevalence of 47.9% (95% Cl 34.0-62.2, I2=99.1%, …

When Unilateral Leg Swelling Is Not Deep Vein Thrombosis: A Case Of Disseminated Kaposi Sarcoma Revealing Advanced Human Immunodeficiency Virus, Ahmed Ismail, Zachary Wilson, Thomas Currow, Michael Dileonardo, Carsten Kirby

Department of Medicine Faculty Publications

Kaposi sarcoma (KS) is an acquired immunodeficiency syndrome (AIDS)-defining malignancy that can involve the skin, lymph nodes, and visceral organs in patients with advanced human immunodeficiency virus (HIV). We report the case of a 35-year-old man with no known prior medical history who presented to the charity care clinic complaining of recurrent thrush and two weeks of progressive right lower extremity swelling. His physical examination revealed painful, pruritic violaceous papules and plaques over the proximal right thigh that had been present for one week. He was referred to the emergency department (ED) for further workup. Venous duplex ultrasonography was negative …

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

Long Covid Incidence Across Sars-Cov-2 Lineages And Identification Of Conserved Spike Targets For Multivalent Vaccines, Grace J. Kim, Md Ashad Alam, Judy S. Crabtree, Rebecca Rose, Susanna L. Lamers, San Chu, Ronald Horswell, Daniel Fort, Lucio Miele

School of Graduate Studies Faculty Publications

Background: Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets. Method: To estimate Long COVID incidence across variants, we linked 4,789 SARS-CoV-2 sequences to 3,090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) …

Presenteeism Among Health Care Personnel With Covid-19, James C. Crosby, Eliezer Santos Leon, Brian Chinnock, Karisa K. Harland, Anusha Krishnadasan, Nicholas M. Mohr, Ian D. Plumb, Melissa Briggs Hagen, Kelli Wallace, David A. Talan, Project Prevent Network, Anne Zepeski, Tracy Young, Howard A. Smithline, Lilly C. Lee, Stephen C. Lim, Et Al

School of Medicine Faculty Publications

IMPORTANCE: Presenteeism-defined as continuing to work during an illness-poses a public health risk in the workplace and is especially hazardous within health care institutions where vulnerable patients may be exposed to nosocomial infections. Understanding the frequency and characteristics of health care personnel (HCP) who report presenteeism while ill with COVID-19 may help mitigate SARS-CoV-2 spread in hospitals and other health care institutions. OBJECTIVES: To determine the frequency of presenteeism among HCP with symptomatic COVID-19, and to evaluate the demographic, occupational, and clinical factors associated with it. DESIGN, SETTING, AND PARTICIPANTS: This is an observational cohort study that uses data from …

High Prevalence And Atypical Genotype Distribution Of Oral Human Papillomavirus In An East African Hiv Cohort: A Cross-Sectional Study, Ian G. Munabi, Adriane Kamulegeya, Dunstan Kalanzi, David P. Kateete, Fred Collins Semitala, Catherine-Lutalo Mwesigwa, Samuel Kalungi, Jennifer E. Cameron, Kimon Divaris, William Buwembo

School of Medicine Faculty Publications

BACKGROUND: Globally, Human Papillomavirus type 16 (HPV-16) is the predominant genotype associated with oropharyngeal cancers. However, little is known about the prevalence and type distribution of Oral Human Papillomavirus (OHPV) in people living with HIV (PLWHIV) in the East African region. The objective of this study was to document the prevalence and circulating genotypes of OHPV infection in a large cohort of PLWHIV attending an urban HIV clinic in Eastern Africa METHODS: This was a cross-sectional study among 1,715 participants of the Makerere University Joint AIDS Program clinic, located in Kampala, Uganda, in East Africa. A salivary sample was collected …

Hpv Prevention In Men: A Narrative Review Of Strategies, Risks, And Public Health Implications, Martin S. Lipsky, Bayler Gunnell, Justin Nguyen, Samantha Lee, Geo Wolfe, Man Hung

Institute on Aging Publications

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide, impacting both males and females. In men, HPV causes genital warts, more than 90% of anal cancers, and 60% of oropharyngeal cancers. Given that one in three men are infected with HPV worldwide, there is a pressing need for enhanced public health strategies focusing on prevention. This comprehensive narrative review presents an overview of HPV in men, key risk factors, and primary prevention in men. The most effective preventive measure for HPV in males is vaccination. Males at high risk for HPV include those who smoke, have human immunodeficiency …

Nirsevimab Effectiveness Against Intensive Care Unit Admission For Respiratory Syncytial Virus In Infants - 24 States, December 2024-April 2025, Laura D. Zambrano, Regina M. Simeone, Margaret M. Newhams, Amanda B. Payne, Natasha B. Halasa, Amber O. Orzel-Lockwood, Jemima M. Calixte, Satoshi Kamidani, Hillary Crandall, Melissa A. Cameron, Jennifer E. Schuster, Aline B. Maddux, Kathleen Chiotos, Katherine Irby, Steven L. Shein, Mary Allen Staat, Lora M. Martin, Samina S. Bhumbra, Ryan A. Nofziger, Jigar C. Chauhan, Danielle M. Zerr, Shira J. Gertz, Judith A. Guzman-Cottrill, Michele Kong, Janet R. Hume, Bria M. Coates, Kelly N. Michelson, Tamara T. Bradford, Et Al

School of Medicine Faculty Publications

Respiratory syncytial virus (RSV) is a leading cause of intensive care unit (ICU) admission and respiratory failure among infants (children aged < year) in the United States. In August 2023, CDC’s Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect against RSV-associated lower respiratory tract infection among all infants aged < 8 months born during or entering their first RSV season. Following licensure, nirsevimab effectiveness has been demonstrated against RSV-associated infant hospitalization, but evidence regarding effectiveness against RSV-associated critical illness is limited. In a 27-hospital case-control investigation, nirsevimab effectiveness against both RSV-associated infant ICU admission and acute respiratory failure (illness requiring continuous positive airway pressure, bilevel positive airway pressure, or invasive mechanical ventilation) after hospital admission was evaluated during December 1, 2024-April 15, 2025. Among 457 case-patients who received a positive RSV test result and 302 control patients who received a negative RSV test result admitted to an ICU with respiratory symptoms, 14% and 45%, respectively, had received nirsevimab ≥ 7 days before symptom onset. Nirsevimab was 80% effective (95% CI = 70%-86%) against RSV-associated ICU admission and 83% effective (95% CI = 74%-90%) against acute respiratory failure when received a median of 52 days (IQR = 32-89 days) and 50 days (IQR = 32-86 days) before onset for each respective endpoint. These estimates support the recommendation for use of nirsevimab as a prevention strategy to protect infants against severe outcomes from RSV infection.

Rabies Virus-Vectored Lyme Disease Vaccine Provides Long-Term Protection Against Tick-Transmitted Borrelia Burgdorferi, Shantel Rios, Bibek Bhattachan, Christoph Wirblich, Anisha Chandwani, Kruthi Vavilikolanu, Jacob F. Myers, Chrysoula Kitsou, Utpal Pal, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Lyme disease (LD) cases have doubled globally. LD is a tick-borne illness caused by the Borrelia burgdorferi sensu lato (Bb). If untreated, Bb can disseminate to distal organs, causing carditis, arthritis, and meningitis. Currently, no FDA-approved human LD vaccine exists on the market. This study used two approaches to incorporate OspA into the rabies virus (RABV) vaccine vector. We used the RABV-glycoprotein tail (RVG tail) and the Hendra virus (HeV) glycoprotein tail (HVG tail) to incorporate OspA, creating BNSP333-OspA-RVG and BNSP333-OspA-HVG, respectively. Both vaccines produced type-1 biased anti-OspA antibodies, but only BNSP333-OspA-HVG induced neutralizing antibodies and protected against Bb infection. …

Allosteric Control Overcomes Steric Limitations For Neutralizing Antibodies Targeting Conserved Binding Epitopes Of The Sars-Cov-2 Spike Protein: Exploring The Intersection Of Binding, Allostery, And Immune Escape With A Multimodal Computational Approach, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Understanding the atomistic basis of multi-layer mechanisms employed by broadly reactive neutralizing antibodies of the SARS-CoV-2 spike protein without directly blocking receptor engagement remains an important challenge in coronavirus immunology. Class 4 antibodies represent an intriguing case: they target a deeply conserved, cryptic epitope on the receptor-binding domain yet exhibit variable neutralization potency across subgroups F1 (CR3022, EY6A, COVA1-16), F2 (DH1047), and F3 (S2X259). The molecular basis for this variability is not fully understood. Here, we employed a multi-modal computational approach integrating atomistic and coarse-grained molecular dynamics simulations, binding free energy calculations, mutational scanning, and dynamic network analysis to elucidate …

Zika Virus Impairs Autophagic Flux In Trabecular Meshwork, And Inhibition Of Autophagy Restricts Ocular Viral Transmission And Associated Pathology, Faraz Ahmad, Prince Kumar, Pallav Singh, Trupti Joshi, Pawan Kumar Singh

Biomedical Sciences

Zika virus (ZIKV) is the lone member of Flavivirus family known to cause congenital glaucoma following in utero exposure. The molecular mechanisms of ZIKV-induced glaucoma remain elusive, with no known therapeutic modalities. Autophagy plays a dual role in viral infections and glaucoma pathogenesis. However, how ZIKV  interferes with autophagic pathways in the trabecular meshwork (TM) and whether autophagy contributes to ZIKV-induced ocular complications remains elusive. Here, we investigated the role of autophagy in ZIKV ocular pathogenesis utilizing a primary human trabecular meshwork cells (HTMC) and IFNAR1-/- mouse model of ocular infection. Our results show that ZIKV permissively infects HTMC, elicits …

Hiv-1 Controllers Possess A Unique Cd8+ T Cell Activation Phenotype And Loss Of Control Is Associated With Increased Expression Of Exhaustion Markers, Amber D. Jones, Zachary Capriotti, Erin Santos, Angel Lin, Rachel Van Duyne, Stephen Smith, Zachary Klase

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

BACKGROUND: HIV-1 controllers are a rare population of individuals that exhibit spontaneous control of HIV-1 infection without antiretroviral therapy. Understanding the mechanisms by which HIV-1 controllers maintain and eventually lose this ability would be highly valuable in HIV-1 cure or vaccine research. Previous work revealed the ability of CD8+ T cells isolated from HIV-1 controllers to suppress HIV-1 replication in matched CD4+ T cells and PBMCs ex vivo and suggested the loss of control may be tied to CD8+ T cell exhaustion.

RESULTS: We explored whether CD8+ T cell exhaustion plays a role in the maintenance and loss of control …

Variability In Long Covid Definitions And Validation Of Published Prevalence Rates, Lauren E. Wisk, Michelle L'Hommedieu, Kate Diaz Roldan, Imtiaz Ebna Mannan, Erica S. Spatz, Robert A. Weinstein, Arjun K. Venkatesh, Michael Gottlieb, Ryan Huebinger, Kristin L. Rising, Juan Carlos C. Montoy, Kari A. Stephens, Robert M. Rodriguez, Mandy J. Hill, Kelli N. O'Laughlin, Nicole L. Gentile, Ahamed H. Idris, Shu-Xia Li, Michelle Santangelo, Efrat R. Kean, Samuel A. Mcdonald, Kristyn Gatling, Joann G Elmore

Jefferson Center for Connected Care Faculty Papers

IMPORTANCE: Long COVID definitions vary widely, and no consensus exists on how to accurately measure its prevalence, complicating both clinical care and research.

OBJECTIVE: To assess long COVID prevalence using various definitions from published literature.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter cohort study used data from the longitudinal Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE). Participants aged 18 years or older with symptoms suggestive of COVID-19 illness at the time of their index SARS-CoV-2 test enrolled at 8 sites across the US from December 11, 2020, through August 29, 2022, with follow-up surveys collected through February 28, …

Dynamic Mutational Profiling Of Binding Interactions And Allosteric Networks In Conformational Ensembles Of The Sars-Cov-2 Spike Protein Complexes With Classes Of Antibodies Targeting Cryptic Binding Sites: Confluence Of Binding And Allostery Determines Molecular Mechanisms And Hotspots Of Immune Escape, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The ongoing evolution of SARS-CoV-2 variants has underscored the need to understand not only the structural basis of antibody recognition but also the dynamic and allosteric mechanisms that could underlie complexity of broad and escape-resistant neutralization. In this study, we employed a multi-scale approach integrating structural analysis, hierarchical molecular simulations, mutational scanning and network-based allosteric modeling to dissect how Class 4 antibodies (represented by S2X35, 25F9, and SA55) and Class 5 antibodies (represented by S2H97, WRAIR-2063 and WRAIR-2134) can modulate conformational behavior, binding energetics, allosteric interactions and immune escape patterns of the SARS-CoV-2 spike protein. Using hierarchical simulations of the …