Infectious Disease Commons^™

Anr And Its Activation By Plch Activity In Pseudomonas Aeruginosa Host Colonization And Virulence, Angelyca A. Jackson, Maegan J. Gross, Emily F. Daniels, Thomas H. Hampton, John H. Hammond, Isabelle Vallet-Gely, Simon L. Dove, Bruce A. Stanton, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ΔplcHR mutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine …

History And Hope: The International Humanitarian Reader, Kevin M. Cahill, M.D.

Institute of International Humanitarian Affairs

History and Hope: The International Humanitarian Reader provides a better understanding—both within and outside academia—of the multifaceted demands posed by humanitarian assistance programs. The Reader is a compilation of the most important chapters in the twelve-volume International Humanitarian Affairs book series published by Fordham University Press. Each selected chapter has been edited and updated. In addition, the series editor, Kevin M. Cahill, M.D., has written, among other chapters, an introductory essay explaining the academic evolution of the discipline of humanitarian assistance. It focuses on the “Fordham Experience”: its Institute of International Humanitarian Affairs (IIHA) has developed practical programs for training …

Antibody Quality And Protection From Lethal Ebola Virus Challenge In Nonhuman Primates Immunized With Rabies Virus Based Bivalent Vaccine., Joseph E Blaney, Andrea Marzi, Mallory Willet, Amy B Papaneri, Christoph Wirblich, Friederike Feldmann, Michael Holbrook, Peter Jahrling, Heinz Feldmann, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced …

Listeria Monocytogenes Cholecystitis: A Possible New Syndrome., Jackrapong Bruminhent, Timothy K Lynch, Jonathan Gefen, Jerome Santoro

Division of Internal Medicine Faculty Papers & Presentations

: The U.S. Food and Drug Administration recently added potentially fatal Listeria monocytogenes infection to the list of opportunistic infections that can occur in patients who receive tumor necrosis factor inhibitor therapy. In this study, the first reported case of L monocytogenes cholecystitis associated with etanercept use is described. It also appears that tumor necrosis factor inhibitor therapy likely increases the risk for Listeria cholecystitis. Clinicians need to be aware of this association when selecting antimicrobial therapy for these patients.

Beliefs About Complementary And Alternative Medicine In Hiv-Infected Black Women Using The Theory Of Planned Behavior, Stephanie G. Lino

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Black women make up 12% of the female population in the U.S, yet they account for 66% of new HIV infections. In 2002, AIDS was the most cited reason for death among Black women age 25-34. While prevention remains, a major effort targeting treatment efficacy and modalities for this sub-group need to be better understood.

Purpose. The purpose of this study is to assess whether HIV-positive Black women’s attitudes, subjective norms and perceived behavioral control are related to intention of dietary supplements and spiritual practices use in their HIV treatment.

Method. In phase one, Grounded Theory methods (N= …

Effects Of Clostridium Difficile On The Human Immune Response, Mike Mcgovern

Honors Projects in Science and Technology

Clostridium difficile is a bacterium that is rapidly becoming a large issue in the medical community due to its tendency to infect hospital patients and its resistance to antibiotics. By studying the way in which the pathogen interacts with the human immune system, it is possible to better understand how the body naturally fights off the disease. This knowledge can allow medical professionals to develop treatments that can help curtail the infection before serious symptoms occur. Working under a grant program alongside Professors Kirsten Hokeness and Chris Reid, I was able to research the effects that exposure to the C. …

Perception Of Disease Risk And Vulnerability As A Function Of Proximity To National Park Boundaries In East Africa, Irene Bridget Feretti

Honors Theses and Capstones

Studies suggest households closest to parks and protected areas (PAs) are more likely to sustain park-related losses, but the relationship between human sickness and PAs has not been fully explored. Existing literature primarily focuses on human-wildlife conflicts (i.e. crop raiding) and the potential for zoonotic disease spillover and emergence at the human-livestock-wildlife interface at PA boundaries. Understanding local perceptions of disease risk and vulnerability is essential for assessing human health relative to conservation areas. This understanding will promote better-informed consideration of human health impacts in decision making for conservation. Data from surveys taken at 301 households around Kibale National Park …

Infective Endocarditis In The U.S., 1998–2009: A Nationwide Study, David H. Bor, Steffie Woolhandler, Rachel Nardin, David Brusch, David U. Himmelstein

Publications and Research

Background
Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates.

Methods and Findings
Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients …

First Steps Phase I Initiative: Improving Immunizations For Children And Adolescents, Kimberley S. Fox Mpa, Carolyn E. Gray Mph

Population Health & Health Policy

This evalution report, authored by research staff at the USM Muskie School, assesses the change in immunization rates in participating pediatric and family practices that serve a high volume of children insured by MaineCare (Maine's Medicaid system). The authors also summarize lessons learned in implementing changes in practices and challenges in using the immunization measures at the practice-level to inform quality improvement.

Lps And Pan-Induced Podocyte Injury In An In Vitro Model Of Minimal Change Disease: Changes In Tlr Profile., Tarak Srivastava, Mukut Sharma, Kok-Hooi Yew, Ram Sharma, R Scott Duncan, Moin A. Saleem, Ellen T. Mccarthy, Alexander Kats, Patricia A. Cudmore, Uri S. Alon, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement …

Inflammatory Biomarker Changes And Their Correlation With Framingham Cardiovascular Risk And Lipid Changes In Antiretroviral-Naive Hiv-Infected Patients Treated For 144 Weeks With Abacavir/Lamivudine/Atazanavir With Or Without Ritonavir In Aries., Benjamin Young, Kathleen E Squires, Lisa L Ross, Lizette Santiago, Louis M Sloan, Henry H Zhao, Brian C Wine, Gary E Pakes, David A Margolis, Mark S Shaefer

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Propensity for developing coronary heart disease (CHD) is linked with Framingham-defined cardiovascular risk factors and elevated inflammatory biomarkers. Cardiovascular risk and inflammatory biomarkers were evaluated in ARIES, a Phase IIIb/IV clinical trial in which 515 antiretroviral-naive HIV-infected subjects initially received abacavir/lamivudine + atazanavir/ritonavir for 36 weeks. Subjects who were virologically suppressed by week 30 were randomized 1:1 at week 36 to either maintain or discontinue ritonavir for an additional 108 weeks. Framingham 10-year CHD risk scores (FRS) and risk category of

Enhancing Communication Between Scientists, Government Officials, And The Lay Public: Advancing Science And Protecting The Public's Welfare Through Better Multi-Stakeholder Interfacing, Clark J. Lee, Patrick P. Rose, Earl Stoddard Iii

Homeland Security Publications

No abstract provided.

A Novel, Network-Wide Outpatient Generational Urine Antibiogram, Jarrod W. Kile Rphd, Lalita G. Shastry Md

Department of Pharmacy

No abstract provided.

Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis …

The Highly Conserved Layer-3 Component Of The Hiv-1 Gp120 Inner Domain Is Critical For Cd4-Required Conformational Transitions, Anik Désormeaux, Mathieu Coutu, Halima Medjahed, Beatriz Pacheco, Alon Herschhorn, Christopher Gu, Shi-Hua Xiang, Youdong Mao, Joseph Sodroski, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates virus entry into host cells. CD4 engagement with the gp120 exterior envelope glycoprotein subunit represents the first step during HIV-1 entry. CD4-induced conformational changes in the gp120 inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 1 and layer 2 have been shown to facilitate the transition of the envelope glycoprotein trimer from the unliganded to the CD4-bound state and to stabilize gp120-CD4 interaction. However, our understanding of CD4-induced conformational changes in the gp120 inner domain remains incomplete. Here, …

Molecular Architecture Of The Uncleaved Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Luis Castillo-Menendez, Liping Wang, Christopher Gu, Alon Herschhorn, Anik Désormeaux, Andrés Finzi, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer, a membrane-fusing machine, mediates virus entry into host cells and is the sole virusspecific target for neutralizing antibodies. Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state. We used cryo-electron microscopy to obtain a 6-Å structure of the membranebound, heavily glycosylated HIV-1 Env trimer in its uncleaved and unliganded state. The spatial organization of secondary structure elements reveals that the unliganded conformations of both gp120 and gp41 subunits differ from those induced by receptor binding. The gp120 trimer association domains, which …

A Twin-Cysteine Motif In The V2 Region Of Gp120 Is Associated With Siv Envelope Trimer Stabilization, Christopher Bohl, Dane Bowder, Jesse Thompson, Levon Abrahamyan, Sandra Gonzalez-Ramirez, Youdong Mao, Joseph Sodroski, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (‘‘twin cysteines’’) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIV_cpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and …

Hiv-1 Env C2-V4 Diversification In A Slow-Progressor Infant Reveals A Flat But Rugged Fitness Landscape, S. Abigail Smith, Charles Wood, John T. West

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type-1 (HIV-1) fitness has been associated with virus entry, a process mediated by the envelope glycoprotein (Env). We previously described Env genetic diversification in a Zambian, subtype C infected, slow-progressor child (1157i) in parallel with an evolving neutralizing antibody response. Because of the role the Variable-3 loop (V3) plays in transmission, cell tropism, neutralization sensitivity, and fitness, longitudinally isolated 1157i C2-V4 alleles were cloned into HIV-1_NL4-3-eGFP and -DsRed2 infectious molecular clones. The fluorescent reporters allowed for dual-infection competitions between all patient-derived C2-V4 chimeras to quantify the effect of V3 diversification and selection on fitness. ‘Winners’ …

‘‘Megavirales’’, A Proposed New Order For Eukaryotic Nucleocytoplasmic Large Dna Viruses, Philippe Colson, Xavier De Lamballerie, Natalya Yutin, Sassan Asgari, Yves Bigot, Dennis K. Bideshi, Xiao-Wen Cheng, Brian A. Federici, James L. Van Etten, Eugene V. Koonin, Bernard La Scola, Didier Raoult

Nebraska Center for Virology: Faculty Publications

The nucleocytoplasmic large DNA viruses (NCLDVs) comprise a monophyletic group of viruses that infect animals and diverse unicellular eukaryotes. The NCLDV group includes the families Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Mimiviridae and the proposed family ‘‘Marseilleviridae’’. The family Mimiviridae includes the largest known viruses, with genomes in excess of one megabase, whereas the genome size in the other NCLDV families varies from 100 to 400 kilobase pairs. Most of the NCLDVs replicate in the cytoplasm of infected cells, within so-called virus factories. The NCLDVs share a common ancient origin, as demonstrated by evolutionary reconstructions that trace approximately 50 genes encoding …

Variations In The Biological Functions Of Hiv-1 Clade C Envelope In A Shiv-Infected Rhesus Macaque During Disease Progression, For Yue Tso, Levon Abrahamyan, Shiu-Lok Hu, Ruth M. Ruprecht, Charles Wood

Nebraska Center for Virology: Faculty Publications

A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection …