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Severity Of Disease And Mortality For Hospitalized Patients With Community-Acquired Viral Pneumonia Compared To Patients With Community-Acquired Bacterial Pneumonia, Richard Y. Kim, Thomas Chandler, Stephen P. Furmanek, Timothy Lee Wiemken, Rodrigo Cavallazzi 2019 University of Louisville

Severity Of Disease And Mortality For Hospitalized Patients With Community-Acquired Viral Pneumonia Compared To Patients With Community-Acquired Bacterial Pneumonia, Richard Y. Kim, Thomas Chandler, Stephen P. Furmanek, Timothy Lee Wiemken, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

Background: There exists a large body of literature to help identify, diagnose, treat, and manage community-acquired pneumonia (CAP). Despite this, there is little data that directly compares the clinical syndromes and complications of pure bacterial pneumonia to pure viral pneumonia. Our study compares the clinical presentation, morbidity and mortality of viral vs. bacterial etiologies of CAP.

Methods: This was a secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) international study database. Data was collected concerning patient demographics, physical examination findings, laboratory findings, radiological findings, severity of illness, and clinical outcomes and stratified according to the two study groups, CAVP ...


Principles For Enhancing Virus Capsid Capacity And Stability From A Thermophilic Virus Capsid Structure, Nicholas P. Stone, Gabriel Demo, Emily Agnello, Brian A. Kelch 2019 University of Massachusetts Medical School

Principles For Enhancing Virus Capsid Capacity And Stability From A Thermophilic Virus Capsid Structure, Nicholas P. Stone, Gabriel Demo, Emily Agnello, Brian A. Kelch

University of Massachusetts Medical School Faculty Publications

The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we used cryoelectron microscopy to determine the capsid structure of the thermostable phage P74-26. We find the P74-26 capsid exhibits an overall architecture that is very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid ...


Protective Versus Pathologic Pre-Exposure Cytokine Profiles In Dengue Virus Infection, Heather Friberg, Coreen M. Beaumier, Sangshin Park, Pamela P. Pazoles, Timothy P. Endy, Anuja Mathew, Jeffrey R. Currier, Richard G. Jarman, Kathryn B. Anderson, Steven Hatch, Stephen J. Thomas, Alan L. Rothman 2018 Walter Reed Army Institute of Research

Protective Versus Pathologic Pre-Exposure Cytokine Profiles In Dengue Virus Infection, Heather Friberg, Coreen M. Beaumier, Sangshin Park, Pamela P. Pazoles, Timothy P. Endy, Anuja Mathew, Jeffrey R. Currier, Richard G. Jarman, Kathryn B. Anderson, Steven Hatch, Stephen J. Thomas, Alan L. Rothman

Open Access Articles

BACKGROUND: Hyperendemic circulation of all four types of dengue virus (DENV-1-4) has expanded globally, fueling concern for increased incidence of severe dengue. While the majority of DENV infections are subclinical, epidemiologic studies suggest that type-cross-reactive immunity can influence disease outcome in subsequent infections. The mechanisms controlling these differential clinical outcomes remain poorly defined.

METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were collected from a cohort of school-aged Thai children who subsequently experienced a subclinical DENV infection or developed dengue illness. PBMC collected prior to infection were stimulated in vitro with DENV and the secretion of 30 cytokines was measured using a multiplexed ...


Resistance From Afar: Distal Mutation V36m Allosterically Modulates The Active Site To Accentuate Drug Resistance In Hcv Ns3/4a Protease, Aysegul Ozen, Kuan-Hung Lin, Keith P. Romano, Davide Tavella, Alicia Newton, Christos J. Petropoulos, Wei Huang, Cihan Aydin, Celia A. Schiffer 2018 University of Massachusetts Medical School

Resistance From Afar: Distal Mutation V36m Allosterically Modulates The Active Site To Accentuate Drug Resistance In Hcv Ns3/4a Protease, Aysegul Ozen, Kuan-Hung Lin, Keith P. Romano, Davide Tavella, Alicia Newton, Christos J. Petropoulos, Wei Huang, Cihan Aydin, Celia A. Schiffer

University of Massachusetts Medical School Faculty Publications

Hepatitis C virus rapidly evolves, conferring resistance to direct acting antivirals. While resistance via active site mutations in the viral NS3/4A protease has been well characterized, the mechanism for resistance of non-active site mutations is unclear. R155K and V36M often co-evolve and while R155K alters the electrostatic network at the binding site, V36M is more than 13 Angstrom away. In this study the mechanism by which V36M confers resistance, in the context of R155K, is elucidated with drug susceptibility assays, crystal structures, and molecular dynamics (MD) simulations for three protease inhibitors: telaprevir, boceprevir and danoprevir. The R155K and R155K ...


Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. McCauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban 2018 University of Massachusetts Medical School

Intron-Containing Rna From The Hiv-1 Provirus Activates Type I Interferon And Inflammatory Cytokines, Sean M. Mccauley, Kyusik Kim, Anetta Nowosielska, Ann Dauphin, Leonid Yurkovetskiy, William E. Diehl, Jeremy Luban

Open Access Articles

HIV-1-infected people who take drugs that suppress viremia to undetectable levels are protected from developing AIDS. Nonetheless, HIV-1 establishes proviruses in long-lived CD4(+) memory T cells, and perhaps other cell types, that preclude elimination of the virus even after years of continuous antiviral therapy. Here we show that the HIV-1 provirus activates innate immune signaling in isolated dendritic cells, macrophages, and CD4(+) T cells. Immune activation requires transcription from the HIV-1 provirus and expression of CRM1-dependent, Rev-dependent, RRE-containing, unspliced HIV-1 RNA. If rev is provided in trans, all HIV-1 coding sequences are dispensable for activation except those cis-acting sequences required ...


Community-Acquired Pneumonia In Adults: Diagnostic Reliability Of Physical Examination Techniques And Their Teaching In Academia, Amber Tordoff, Lauren A. Williams 2018 James Madison University

Community-Acquired Pneumonia In Adults: Diagnostic Reliability Of Physical Examination Techniques And Their Teaching In Academia, Amber Tordoff, Lauren A. Williams

Physician Assistant Capstones

Background: Chest physical examination techniques are taught in academia, but their usefulness in the evaluation and diagnosis of patients in the clinical setting is controversial. Objective: To investigate the accuracy of physical examination techniques and their reliability in diagnosing community acquired pneumonia (CAP) and suggest a modified teaching approach to be used in academia. Design: Systematic Literature Review. Methods: Database search of PubMed and Google Scholar using the search terms “prediction of pneumonia in adults” and “prediction rule for pulmonary infiltrates.” Filters were implemented to include articles that only dealt with human subjects and were full text. Articles were excluded ...


Upregulation Of Hla-E By Dengue And Not Zika Viruses, Elena Drews, Awadalkareem Adam, Phone Htoo, Elizabeth Townsley, Anuja Mathew 2018 University of Massachusetts Medical School

Upregulation Of Hla-E By Dengue And Not Zika Viruses, Elena Drews, Awadalkareem Adam, Phone Htoo, Elizabeth Townsley, Anuja Mathew

Open Access Articles

Introduction: The most severe form of dengue virus (DENV) illness, dengue haemorrhagic fever, is characterised by plasma leakage and increased vascular permeability.

Objectives: Given the critical role that endothelial cells play in the pathogenesis of DENV, we wanted to determine whether infection with DENV altered the expression of MHC class I related genes including HLA-E.

Results: In this study, we provide evidence that HLA-E but not MICA/B or HLA-G is upregulated by all four serotypes of DENV in an endothelial cell line human microvascular endothelial cells (HMEC)-1. In contrast, Zika virus (ZIKV), a related flavivirus, where plasma leakage ...


All-In-One Adeno-Associated Virus Delivery And Genome Editing By Neisseria Meningitidis Cas9 In Vivo, Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer 2018 University of Massachusetts Medical School

All-In-One Adeno-Associated Virus Delivery And Genome Editing By Neisseria Meningitidis Cas9 In Vivo, Raed Ibraheim, Chun-Qing Song, Aamir Mir, Nadia Amrani, Wen Xue, Erik J. Sontheimer

RNA Therapeutics Institute Publications

BACKGROUND: Clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) have recently opened a new avenue for gene therapy. Cas9 nuclease guided by a single-guide RNA (sgRNA) has been extensively used for genome editing. Currently, three Cas9 orthologs have been adapted for in vivo genome engineering applications: Streptococcus pyogenes Cas9 (SpyCas9), Staphylococcus aureus Cas9 (SauCas9), and Campylobacter jejuni (CjeCas9). However, additional in vivo editing platforms are needed, in part to enable a greater range of sequences to be accessed via viral vectors, especially those in which Cas9 and sgRNA are combined into a single vector genome.

RESULTS: Here ...


Select Gp120 V2 Domain Specific Antibodies Derived From Hiv And Siv Infection And Vaccination Inhibit Gp120 Binding To Alpha4beta7, Sakaorat Lertjuthaporn, Shan Lu, Yang Lou, Shixia Wang, James Arthos 2018 Mahidol University

Select Gp120 V2 Domain Specific Antibodies Derived From Hiv And Siv Infection And Vaccination Inhibit Gp120 Binding To Alpha4beta7, Sakaorat Lertjuthaporn, Shan Lu, Yang Lou, Shixia Wang, James Arthos

Open Access Articles

The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin alpha4beta7, a gut-homing receptor. Using both cell-surface expressed alpha4beta7 and a soluble alpha4beta7 heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of alpha4beta7 in a cation -sensitive manner and is inhibited ...


Herpes Icp8 Protein Stimulates Homologous Recombination In Human Cells, Melvys Valledor, Richard S. Myers, Paul C. Schiller 2018 University of Massachusetts Medical School

Herpes Icp8 Protein Stimulates Homologous Recombination In Human Cells, Melvys Valledor, Richard S. Myers, Paul C. Schiller

Open Access Articles

Recombineering has transformed functional genomic analysis. Genome modification by recombineering using the phage lambda Red homologous recombination protein Beta in Escherichia coli has approached 100% efficiency. While highly efficient in E. coli, recombineering using the Red Synaptase/Exonuclease pair (SynExo) in other organisms declines in efficiency roughly correlating with phylogenetic distance from E. coli. SynExo recombinases are common to double-stranded DNA viruses infecting a variety of organisms, including humans. Human Herpes virus 1 (HHV1) encodes a SynExo comprised of ICP8 synaptase and UL12 exonuclease. In a previous study, the Herpes SynExo was reconstituted in vitro and shown to catalyze a ...


Using Clinical Decision Support Within The Electronic Health Record To Reduce Incorrect Prescribing For Acute Sinusitis, Regina Ginzburg, Justin J. Conway, Eve Waltermaurer, Wendy Song, Samantha P. Jellinek-Cohen 2018 College of Pharmacy and Health Sciences, St. John's University; Institute for Family Health

Using Clinical Decision Support Within The Electronic Health Record To Reduce Incorrect Prescribing For Acute Sinusitis, Regina Ginzburg, Justin J. Conway, Eve Waltermaurer, Wendy Song, Samantha P. Jellinek-Cohen

Journal of Patient-Centered Research and Reviews

Purpose: Acute sinusitis has viral etiology in more than 90% of cases, but antibiotics are prescribed for more than 80% of adults in the United States. While applications of computer-assisted guidelines have been found effective in reducing inaccurate prescribing for acute respiratory infections, there is a paucity of research focused specifically on the utilization of electronic best practice alerts (BPA) in improving treatment for acute sinusitis.

Methods: This observational cohort study examined prescribing behavior for sinusitis at a single Federally Qualified Health Center 1 year prior and during the first year of implementation of a BPA in the electronic health ...


Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif 2018 University of Nebraska-Lincoln

Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif

Dissertations & Theses in Veterinary and Biomedical Science

Bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV) infections contribute to the bovine respiratory disease complex (BRDC), which is a multi-factorial disorder involving co-infections of viruses and bacteria including mycoplasma. BRDC causes great economic losses to the United States feedlot industry. BVDV infection induces immunosuppression in infected animals. BVDV Npro binds and degrades the transcription factor interferon regulatory factor-3 (IRF-3) and effectively blocks type I interferon (type I IFN) expression in host cells. BRSV nonstructural proteins, NS1 and NS2, block activation of IRF-3. In calves, concurrent infection with BVDV and BRSV resulted in more severe clinical signs ...


Direct Cell-To-Cell Transmission Of Respiratory Viruses: The Fast Lanes, Nicolás P. Cifuentes-Muñoz, Rebecca Ellis Dutch, Roberto Cattaneo 2018 University of Kentucky

Direct Cell-To-Cell Transmission Of Respiratory Viruses: The Fast Lanes, Nicolás P. Cifuentes-Muñoz, Rebecca Ellis Dutch, Roberto Cattaneo

Molecular and Cellular Biochemistry Faculty Publications

Virus particles protect genomes from hostile environments within and outside the host, eventually delivering these genomes to target tissues to initiate infection. Complex processes requiring significant energy and time are necessary to assemble these virus particles, but only a small portion of released virus will successfully infect new target cells (Fig 1A). While the science of virology has developed based on the isolation and purification of viral particles, it is becoming increasingly clear that direct cell-to-cell transmission of viruses and/or viral components is also highly relevant [1,2].

Direct cell-to-cell spread of infections has several advantages. The first is ...


Crystal Structure Of The Catalytic Domain Of Hiv-1 Restriction Factor Apobec3g In Complex With Ssdna, Atanu Maiti, Wazo Myint, Tapan Kanai, Krista Delviks-Frankenberry, Christina Sierra Rodriguez, Vinay K. Pathak, Celia A. Schiffer, Hiroshi Matsuo 2018 Frederick National Laboratory for Cancer Research

Crystal Structure Of The Catalytic Domain Of Hiv-1 Restriction Factor Apobec3g In Complex With Ssdna, Atanu Maiti, Wazo Myint, Tapan Kanai, Krista Delviks-Frankenberry, Christina Sierra Rodriguez, Vinay K. Pathak, Celia A. Schiffer, Hiroshi Matsuo

Open Access Articles

The human APOBEC3G protein is a cytidine deaminase that generates cytidine to deoxy-uridine mutations in single-stranded DNA (ssDNA), and capable of restricting replication of HIV-1 by generating mutations in viral genome. The mechanism by which APOBEC3G specifically deaminates 5'-CC motifs has remained elusive since structural studies have been hampered due to apparently weak ssDNA binding of the catalytic domain of APOBEC3G. We overcame the problem by generating a highly active variant with higher ssDNA affinity. Here, we present the crystal structure of this variant complexed with a ssDNA substrate at 1.86 A resolution. This structure reveals atomic-level interactions ...


Phytobiological Warfare: An Evolutionary Approach To Botanical Medicine, Guillermo Ruiz NMD, Tiffany Turner, Jeffrey Langland 2018 Southwest College of Naturopathic Medicine

Phytobiological Warfare: An Evolutionary Approach To Botanical Medicine, Guillermo Ruiz Nmd, Tiffany Turner, Jeffrey Langland

Journal of Evolution and Health

No abstract provided.


Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori McGinnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison 2018 Sigmovir Biosystems Inc.

Efficacy Of A Respiratory Syncytial Virus Vaccine Candidate In A Maternal Immunization Model, Jorge C. G. Blanco, Lioubov M. Pletneva, Lori Mcginnes Cullen, Raymonde O. Otoa, Mira C. Patel, Lurds R. Fernando, Marina S. Boukhvalova, Trudy G. Morrison

Open Access Articles

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Maternal immunization is an option to increase maternal antibody levels and protect infants from infection. Here we assess the efficacy of virus-like particle (VLP) vaccine candidates containing stabilized pre-fusion (pre-F) or post-fusion (post-F) conformations of the RSV F protein and the attachment RSV G protein in a maternal immunization model using cotton rats. VLP vaccines containing RSV F and G proteins strongly boost pre-existing RSV immunity in dams preventing their perinatal drop in immunity. Boosting is stronger for the pre-F VLP than for the post-F VLP or ...


Ictv Virus Taxonomy Profile: Hypoviridae, Nobuhiro Suzuki, Said A. Ghabrial, Kook-Hyung Kim, Michael Pearson, Shin-Yi L. Marzano, Hajime Yaegashi, Jiatao Xie, Lihua Guo, Hideki Kondo, Igor Koloniuk, Bradley I. Hillman, ICTV Report Consortium 2018 Okayama University, Japan

Ictv Virus Taxonomy Profile: Hypoviridae, Nobuhiro Suzuki, Said A. Ghabrial, Kook-Hyung Kim, Michael Pearson, Shin-Yi L. Marzano, Hajime Yaegashi, Jiatao Xie, Lihua Guo, Hideki Kondo, Igor Koloniuk, Bradley I. Hillman, Ictv Report Consortium

Plant Pathology Faculty Publications

The Hypoviridae, comprising one genus, Hypovirus, is a family of capsidless viruses with positive-sense, ssRNA genomes of 9.1–12.7 kb that possess either a single large ORF or two ORFs. The ORFs appear to be translated from genomic RNA by non-canonical mechanisms, i.e. internal ribosome entry site-mediated and stop/restart translation. Hypoviruses have been detected in ascomycetous or basidiomycetous filamentous fungi, and are considered to be replicated in host Golgi-derived, lipid vesicles that contain their dsRNA as a replicative form. Some hypoviruses induce hypovirulence to host fungi, while others do not. This is a summary of the ...


Micro Rnas From Dna Viruses Are Found Widely In Plasma In A Large Observational Human Population, Milka Koupenova-Zamor, Eric O. Mick, Heather A. Corkrey, Tianxiao Huan, Lauren Clancy, Ravi Shah, Emelia J. Benjamin, Daniel Levy, Evelyn A. Kurt-Jones, Kahraman Tanriverdi, Jane E. Freedman 2018 University of Massachusetts Medical School

Micro Rnas From Dna Viruses Are Found Widely In Plasma In A Large Observational Human Population, Milka Koupenova-Zamor, Eric O. Mick, Heather A. Corkrey, Tianxiao Huan, Lauren Clancy, Ravi Shah, Emelia J. Benjamin, Daniel Levy, Evelyn A. Kurt-Jones, Kahraman Tanriverdi, Jane E. Freedman

Open Access Articles

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae. These miRNAs were mostly related to viral latency and have not been previously detected in human plasma. Viral miRNA expression was then screened in the plasma of 2763 participants of the remaining cohort utilizing high-throughput RT-qPCR ...


Role Of Protein Charge Density On Hepatitis B Virus Capsid Formation, Xinyu Sun, Dong Li, Zhaoshuai Wang, Panchao Yin, Rundong Hu, Rundong Hu, Hui Li, Qiao Liu, Yunyi Gao, Baiping Ren, Jie Zheng, Yinan Wei, Tianbo Liu 2018 The University of Akron

Role Of Protein Charge Density On Hepatitis B Virus Capsid Formation, Xinyu Sun, Dong Li, Zhaoshuai Wang, Panchao Yin, Rundong Hu, Rundong Hu, Hui Li, Qiao Liu, Yunyi Gao, Baiping Ren, Jie Zheng, Yinan Wei, Tianbo Liu

Chemistry Faculty Publications

The role of electrostatic interactions in the viral capsid assembly process was studied by comparing the assembly process of a truncated hepatitis B virus capsid protein Cp149 with its mutant protein D2N/D4N, which has the same conformational structure but four fewer charges per dimer. The capsid protein self-assembly was investigated under a wide range of protein surface charge densities by changing the protein concentration, buffer pH, and solution ionic strength. Lowering the protein charge density favored the capsid formation. However, lowering charge beyond a certain point resulted in capsid aggregation and precipitation. Interestingly, both the wild-type and D2N/D4N ...


Transmembrane Domains Of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro, Stacy R. Webb, Stacy E. Smith, Michael G. Fried, Rebecca Ellis Dutch 2018 University of Kentucky

Transmembrane Domains Of Highly Pathogenic Viral Fusion Proteins Exhibit Trimeric Association In Vitro, Stacy R. Webb, Stacy E. Smith, Michael G. Fried, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Enveloped viruses require viral fusion proteins to promote fusion of the viral envelope with a target cell membrane. To drive fusion, these proteins undergo large conformational changes that must occur at the right place and at the right time. Understanding the elements which control the stability of the prefusion state and the initiation of conformational changes is key to understanding the function of these important proteins. The construction of mutations in the fusion protein transmembrane domains (TMDs) or the replacement of these domains with lipid anchors has implicated the TMD in the fusion process. However, the structural and molecular details ...


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