Viruses Commons^™

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 similar to 2 mg of one bnAb. In ex vivo porcine skin tests, the MNs effectively penetrated the skin. When tested in vitro in PBS …

Occupational Human Papillomavirus Exposure Risks For Laryngeal Surgeons And Phoniatricians: A Joint European Laryngological Society (Els) And Union Of European Phoniatricians (Uep) Delphi Clinical Consensus Statement, Shiying Hey, Alberto Maria Saibene, Milan Amin, Jennifer Anderson, Christoph Arens, Simon Best, Guillermo Campos, Craig Derkay, Gauthier Desuter, Frederik G. Dikkers, Isabel Garcia-Lopez, Ahmed Geneid, Anastasios Hantzakos, Markus Hess, Yakubu Karagama, Marina Mat Baki, Napur Kapoor Nerurkar, Daniel Novakovic, Haldun Oguz, Shazia Peer, Jasmine Prasad, Carlo Robotti, David Vokes, Chi-Te Wang, Malgorzata Wierzbicka, Michal Zabrodsky, Nicolien Van Der Poel

Department of Otolaryngology (ENT) Faculty Publications

Purpose

Laser surgical management of human papillomavirus (HPV)-related disease, such as recurrent respiratory papillomatosis (RRP), in the upper aerodigestive tract generates surgical smoke, which may represent a source of occupational viral exposure for laryngeal surgeons, phoniatricians, anesthesia providers and scrub nurses. Despite growing awareness, protective measures remain inconsistently implemented. This study aimed to develop an evidence-informed clinical consensus statement (CCS) to guide occupational HPV risk management in laryngology.

Methods

A modified Delphi consensus process was conducted under the auspices of the European Laryngological Society (ELS) and the Union of the European Phoniatricians (UEP). A panel of 26 international experts undertook …

Reply To: Malik Mmud On 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

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] To the Editor:

We thank Professor MMUD Malik [1] for his interest in our recent publication describing the improvements in loss of smell symptoms with tezepelumab versus placebo in patients with uncontrolled chronic rhinosinusitis with nasal polyps in the WAYPOINT trial (NCT04851964) [2]. We appreciate Professor Malik's comments on the language used to describe the findings and the specific analyses presented as well as his note regarding the consistent improvements in sense of smell observed with tezepelumab treatment versus placebo, demonstrated by large effect sizes across three instruments.

Aggressive Natural Killer Cell Leukemia: A Rare And Rapidly Progressive Hematologic Malignancy—Case Report And Literature Review, Jennifer Priessnitz, Ali Hariri, Yuliya Levkiavska, Kyle E. Bonner, Stephan I. Fisher, Joshua M. Sill

Department of Medicine Faculty Publications

Aggressive natural killer cell leukemia (ANKL) is a rare, fulminant hematologic malignancy characterized by neoplastic proliferation of mature NK cells. It is frequently associated with Epstein-Barr virus (EBV) infection, although EBV-negative cases have also been reported. While typically observed in young to middle-aged adults of East Asian descent, increasing recognition has led to identification of ANKL across diverse age groups and ethnicities. The disease is defined by a rapid clinical course and poor prognosis, underscoring the importance of early diagnosis and effective treatment. We present a case of a 71-year-old Caucasian male who developed fever, altered mental status, hepatosplenomegaly, pancytopenia, …

The Ptp4a3 Inhibitor Kvx-053 Reduces Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Virulence, Inflammation, And Development Of Acute Lung Injury In K18-Hace2 Mice, Ruben M. L. Colunga-Biancatelli, Pavel A. Solopov, Caitlin M. Woodson, Irving Coy Allen, Ivan Akhrymuk, Maryna Akhrymuk, Brittany N. Heath, Hannah M. Ivester, Tierney Day, Dan E. Austin, Kylene Kehn-Hall, John S. Lazo, Elizabeth R. Sharlow, John D. Catravas

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global health crisis, marked by high transmissibility and virulence. Despite widespread vaccination efforts, effective treatments for COVID-19, particularly for severe cases leading to Acute Respiratory Distress Syndrome (ARDS), remain limited. This study investigates the efficacy of KVX-053, a protein tyrosine phosphatase type IVA (PTP4A3) small molecule inhibitor, in modulating SARS-CoV-2-induced inflammation and lung injury using in vitro cell models and in vivo K18-hACE2 transgenic mice. KVX-053 reduced in vitro pro-inflammatory cytokine expression, including TNFα, CXCL10, and CXCL11, without impacting viral replication or cell viability. K18-hACE2 mice treated with KVX-053 demonstrated …

Formulation Development Of Dual-Compartment Topical Inserts Combining Tenofovir Alafenamide And Elvitegravir For Flexible On-Demand Hiv Prevention, Vivek Agrahari, M. Melissa Peet, Neelima Chandra, Prakash Ramalingam, Pardeep K. Gupta, Sriramakamal Jonnalagadda, Onkar N. Singh, Timothy J. Mccormick, Gustavo F. Doncel, Meredith R. Clark

Department of Obstetrics & Gynecology Faculty Publications

Pre-exposure prophylaxis (PrEP) has emerged as a prominent approach for the prevention of HIV infections. While the latest advances have resulted in effective oral and injectable product options, there are still gaps in on-demand, event-driven, topical products for HIV prevention that are safe and effective. Here we describe the formulation development of a dual-compartment topical insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) that may be administered when needed, vaginally or rectally, pre- or post-coitus, for flexible HIV prophylaxis. Specifically, we describe the lab-scale formulation development, preclinical mucosal safety and pharmacokinetics (PK) testing in rabbits, long-term stability, and scale-up …

Synthesis And Evaluation Of Anti-Hiv Activity Of Fatty Acyl Conjugates Of Tenofovir Alefanamide, Muhammad Sajid, Naglaa Salem El-Sayed, Louise A. Ouattara, Amita Verma, Gustavo F. Doncel, Keykavous Parang, M. Iqbal Choudhary, Hina Siddiqui

CONRAD Publications

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by intracellular enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent this limitation, several prodrug approaches have been proposed and developed. Herein, we hypothesized that the conjugation of anti-HIV fatty acids with the nucleotide tenofovir alafenamide (TAF) (1) could improve the anti-HIV activity of the nucleotide. Several fatty acyl amide conjugates of TAF were synthesized and evaluated in comparative studies with TAF. The synthesized compounds were evaluated as racemic mixtures for anti-HIV activity in vitro in a single-round HIV-1 infection assay …

Forecasting Covid-19 Cases, Hospital Admissions, And Deaths Based On Wastewater Sars-Cov-2 Surveillance Using Gaussian Copula Time Series Marginal Regression Model, Hueiwang Anna Jeng, Norou Diawara, Cynthia Jackson, Rekha Singh, Kyle Curtis, Raul Gonzalez, David Jurgens, Sasanka Adikari

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Modeling efforts are needed to predict trends in COVID-19 cases and related health outcomes, aiding in the development of management strategies and adaptation measures. This study was conducted to assess whether the SARS-CoV-2 viral load in wastewater could serve as a predictor for forecasting COVID-19 cases, hospitalizations, and deaths using copula-based time series modeling. SARS-CoV-2 RNA load in wastewater in Chesapeake, VA, was measured using the RT-qPCR method. A Gaussian copula time series (CTS) marginal regression model, incorporating an autoregressive moving average model and Gaussian copula function, was used as a forecasting model. Wastewater SARS-CoV-2 viral loads were correlated with …

Interobserver Variability Regarding Adequacy Of Oropharyngeal Exposure For Transoral Robotic Surgery May Necessitate Staging Endoscopy: Evaluating Tors Exposure, Colleen Schinderle, Kevin J. Carlson, Reem Sharaf Alddin, Jeffery J. Houlton, Matthew J. Bak, Daniel W. Karakla, Jonathan R. Mark

Department of Otolaryngology (ENT) Faculty Publications

[First paragraph] Transoral robotic surgery (TORS) for the treatment of oropharyngeal cancer has become centered at tertiary referral centers. To avoid treatment delays or multiple anesthetics, the need for repeat operative endoscopy may be questioned when the diagnosis has been made at an outside institution. However, inadequate visualization of relevant anatomy can preclude TORS candidacy and may lead to procedure abortion or conversion to an open technique.²,³ To evaluate this dilemma, we explored the ability to assess oropharyngeal exposure for TORS candidacy via operative endoscopic photo-documentation.

The Importance Of Solution Studies For The Structural Characterization Of The Enterovirus 5' Cloverleaf, Morgan G. Daniels, Meagan E. Werner, Xiaobing Zuo, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5' cloverleaf (5'CL). Here, we present a biophysical analysis of the 5'CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD spectroscopy, size-exclusion chromatography, and small-angle X-ray scattering. In general, a tendency toward a smaller monomeric hydrodynamic radius in the presence of salts was observed, but the exact structural signature of each 5'CL varied depending upon the serotype. Rhinovirus B14 (RVB14) exhibited at least two monomeric conformations and a low propensity for dimerization, while poliovirus 1 (PV1) showed …

Zika Virus Modulates Arthropod Histone Methylation For Its Survival In Mosquito Cells, Telvin Harrell

Biological Sciences Faculty Publications

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes mild febrile illness in adults and severe neurological complications and microcephaly in newborns. Studies have reported that ZIKV modulates methylation of human and viral RNA critical for its replication in vertebrate cells. In this study, we show that ZIKV modulates mosquito S-adenosyl methionine (SAMe)-synthase, an enzyme involved in the production of SAMe (methyl donor), and histone methylation for its survival in mosquito cells. Reverse transcription quantitative PCR followed by immunoblotting analysis showed increased amounts of SAMe synthase at both RNA and protein levels, respectively, in C6/36 mosquito cells infected with …

Dengue Virus Modulates Critical Cell Cycle Regulatory Proteins In Human Megakaryocyte Cells, Swarnendu Basak, Shovan Dutta, Supreet Khanal, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Suppression of human megakaryocytes by dengue virus (DENV) infection significantly reduces the platelet count that eventually leads to thrombocytopenia, severe dengue and death. To understand DENV interactions with megakaryocytes, we investigated the cell cycle in leukemic human megakaryocytic in vitro cell line (MEG-01 cells). Megakaryocytes are known for complex endomitotic cell cycle leading to their polyploidy state. Our study shows that DENV uses these polyploid cells for its replication. Understanding the modulation of DENV-mediated cell cycle regulation in megakaryocytes is therefore highly important. We show that DENV2 (serotype 2) infection significantly modulates cell cycle signaling. Our protein profile microarray data …

Exploration Of Potential Broad-Spectrum Antiviral Targets In The Enterovirus Replication Element: Identification Of Six Distinct 5' Cloverleaves, Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human health-related serotypes from the enterovirus genus, including enterovirus and rhinovirus species. Phylogenetic analysis indicates six distinct 5′CL serotypes that only partially correlate with the species definition. Additional findings include that 5′CL sequence conservation is higher between the EV species than between the RV species, the 5′CL of EVA and EVB are nearly identical, and RVC has the …

Recent Advances In Research And Management Of Human Monkeypox Virus: An Emerging Global Health Threat, Parveen Kumar, Benu Chaudhary, Nishant Yadav, Sushma Devi, Ashutosh Pareek, Sujatha Alla, Fnu Kajal, Behdin Nowrouzi-Kia, Vijay Kumar Chattu, Madan Mohan Gupta

Engineering Management & Systems Engineering Faculty Publications

In 2003, the United States saw an epidemic of monkeypox that was later traced back to rodents of West Africa infected with the monkeypox virus (MPXV). Disease in the United States seemed less severe than the smallpox-like disease in the Democratic Republic of the Congo (DRC). In this study, researchers analyzed data from Central Africa: two distinct MPXV clades were confirmed by sequencing the genomes of MPXV isolates from Western Africa, the United States, and Central Africa. By comparing open reading frames across MPXV clades, scientists can infer which virus proteins might account for the observed variation in pathogenicity in …

Promiscuous Feeding Across Multiple Honey Bee Hosts Amplifies The Vectorial Capacity Of Varroa Destructor, Zachary S. Lamas, Serhat Solmaz, Eugene V. Ryabov, Joseph Mowery, Matthew Heermann, Daniel Sonenshine, Jay D. Evans, David J. Hawthorne

Biological Sciences Faculty Publications

Varroa destructor is a cosmopolitan pest and leading cause of colony loss of the European honey bee. Historically described as a competent vector of honey bee viruses, this arthropod vector is the cause of a global pandemic of Deformed wing virus, now endemic in honeybee populations in all Varroa-infested regions. Our work shows that viral spread is driven by Varroa actively switching from one adult bee to another as they feed. Assays using fluorescent microspheres were used to indicate the movement of fluids in both directions between host and vector when Varroa feed. Therefore, Varroa could be in either …

Poisson Regression Model With Application To Wastewater Surveillance Under A Threshold Linear Mixed Model For Covid-19 Sensitivity Rates, Norou Diawara, Hueiwang Anna Jeng, Kyle Curtis, Raul Gonzalez, Nancy Welch, Cynthia Jackson, Rekha Singh, David Jurgens, Sasanka Adikari, Omotomilola Jegede

Mathematics & Statistics Faculty Publications

A Threshold Linear Mixed Model (TLMM) has been developed to identify specific thresholds based on wastewater SARS-CoV-2 viral concentrations, which reflect COVID-19 cases. The thresholds can guide decisions regarding public health responses and prevention measures. To assess the practical application of TLMM, a simple simulation was conducted using a sample size of 100 and 500 replications. The simulation allowed for comparing parameter estimators by assessing bias and standard deviation and the root of the mean square error. The model and estimation procedures were applied to reported wastewater and clinic data to test its application for real-world scenarios. Our results demonstrated …

Structural Biology Of The Enterovirus Replication-Linked 5'-Cloverleaf Rna And Associated Virus Proteins, Steven M. Pascal, Ravindranath Garimella, Meghan S. Warden, Komala Ponniah

Chemistry & Biochemistry Faculty Publications

Although enteroviruses are associated with a wide variety of diseases and conditions, their mode of replication is well conserved. Their genome is carried as a single, positive-sense RNA strand. At the 5′ end of the strand is an approximately 90-nucleotide self-complementary region called the 5′ cloverleaf, or the oriL. This noncoding region serves as a platform upon which host and virus proteins, including the 3B, 3C, and 3D virus proteins, assemble in order to initiate replication of a negative-sense RNA strand. The negative strand in turn serves as a template for synthesis of multiple positive-sense RNA strands. Building on structural …

Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest stem–loops within the 5′CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5′CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB …

Zika Virus- Emergence, Evolution, Pathology, Diagnosis, And Control: Current Global Scenario And Future Perspectives- A Comprehensive Review, Raj K. Singh, Kuldeep Dhama, Yashpal S. Malik, Muthannan A. Ramakrishnan, Kumaragurubaran Karthik, Sunil K. Joshi

Bioelectrics Publications

This review converses the Zika virus which has attained global concern due to its rapid pandemic potential and impact on humans. Though Zika virus was first isolated in 1947, till the recent large-scale outbreak which occurred in Micronesia, in 2007, the virus was placed into the innocuous pathogen category. The World Health Organization on 1 February 2016 declared it as a Public Health Emergency of International Concern.' Of the note, American as well as Pacific Island strains/isolates is relatively closer to Asian lineage strains. The African and American strains share more than 87.5% and 95% homologies with Asian strains/isolates, respectively. …

Isolation And Enumeration Of Enteric Viruses From Primary Wastewater Sludge, Michael Wayne Nath

Biological Sciences Theses & Dissertations

The presence of large numbers of enteric viruses in wastewaters has resulted in concern regarding their significance and consequences for humans. Assessments of relative significance or consequences may most accurately be made following precise measurements of the range of virus types and amounts in wastewaters and sludges and after epidemiological considerations. In this study, results are presented pertaining to enteric virus isolation, concentration, and enumeration from primary wastewater sludges.

As an integral part of a comparison of isolation procedures, several anionic surfactants were examined for extraction of enteric viruses from primary wastewater sludges. Plaquing efficiencies for poliovirus type 2 and …

Comparison Of Interferon Produced In Vitro By Monkey Kidney Cells Demonstrating Interference Against Polio Ii, Coxsackie A-9, Influenza A2/Hong Kong/68, And Echo-9 Viruses, Archer Duncan Farmer Jr.

Biological Sciences Theses & Dissertations

Abstract unavailable