Virus Diseases Commons^™

Decreases In Self-Reported Alcohol Consumption Following Hiv Counseling And Testing At Mulago Hospital, Kampala, Uganda, Judith A. Hahn, Robin Fatch, Rhoda K. Wanyenze, Steven Baveewo, Moses R. Kamya, David Bangsberg, Thomas J. Coates

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background: Alcohol use has a detrimental impact on the HIV epidemic, especially in sub-Saharan Africa. HIV counseling and testing (HCT) may provide a contact opportunity to intervene with hazardous alcohol use; however, little is known about how alcohol consumption changes following HCT.

Methods: We utilized data from 2056 participants of a randomized controlled trial comparing two methods of HCT and subsequent linkage to HIV care conducted at Mulago Hospital in Kampala, Uganda. Those who had not previously tested positive for HIV and whose last HIV test was at least one year in the past were eligible. Participants were asked at …

Small-Molecule Probes Targeting The Viral Ppxy-Host Nedd4 Interface Block Egress Of A Broad Range Of Rna Viruses., Ziying Han, Jianhong Lu, Yuliang Liu, Benjamin Davis, Michael S Lee, Mark A Olson, Gordon Ruthel, Bruce D Freedman, Matthias J. Schnell, Jay E Wrobel, Allen B Reitz, Ronald N Harty

Department of Microbiology and Immunology Faculty Papers

Budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by subversion of host proteins, such as Nedd4 E3 ubiquitin ligase, by viral PPxY late (L) budding domains expressed within the matrix proteins of these RNA viruses. As L domains are important for budding and are highly conserved in a wide array of RNA viruses, they represent potential broad-spectrum targets for the development of antiviral drugs. To identify potential competitive blockers, we used the known Nedd4 WW domain-PPxY interaction interface as the basis of an in silico screen. Using PPxY-dependent budding of Marburg (MARV) VP40 virus-like particles (VLPs) as our model system, …

A Transdisciplinary Approach To Eliminate Cancer Disparities: An Overview Of Community Engagement And Outreach Efforts In An National Institute Of Health Center For Excellence, Maisha Standifer, Mph, Julie Baldwin, Phd, Jenna Davis, Mph, Clemente Gwede, Phd, Coni Williams, Ma, Lolita Dash-Pitts, Johnetta Goldsmith, Ms, Thometta Cozart Brooks Ms, Mph, Deanna Wathington, Md, B. Lee Green, Phd, Kevin Sneed, Phamd

Journal of Health Disparities Research and Practice

Creating health equity and eliminating health disparities are considered national priorities for improving the health of Americans (U.S. Department of Health and Human Services, n.d.). Health disparities are a primary public health concern, yet are complex phenomena and challenging to research (Harper & Lynch, 2005). The National Institute on Minority Health and Health Disparities (NIMHD), under the National Institute of Health (NIH), is committed to finding solutions to achieve this goal through the creation of interdisciplinary Centers of Excellence. In 2009, the University of South Florida (USF) and Moffitt Cancer Center (Moffitt) received a NIMHD Exploratory Center of Excellence award …

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …

Oncolytic Tanapoxvirus Expressing Flic Causes Regression Of Human Colorectal Cancer Xenografts In Nude Mice, Steven J. Conrad

Dissertations

Cancers of the colon and rectum are a significant cause of morbidity and mortality worldwide and existing therapies often perform poorly for individuals afflicted with advanced stage disease. Oncolytic virotherapy is an emerging therapeutic modality which shows great promise for addressing this serious medical need. Herein we describe the in vivo testing of recombinant variants of the tanapoxvirus (TPV), a virus endemic to equatorial Africa which causes a mild and self-limiting disease in humans. Recombinant tanapoxviruses were made deleted for the 66R gene, the 2L gene, or both. Some of the recombinants were armed with mouse chemotactic protein 1 (m …

Social Determinants Of Late Presentation To Hiv Care, Connie Leeper, Michael Mugavero, James Willig, Eric Chamot, Shatomi Kerbawy, Anne Zinski

Journal of Health Disparities Research and Practice

Background: In recent years, increased attention has shifted toward evaluating social determinants of health, and understanding how community, environment, and system factors affect health outcomes. HIV policies and guidelines emphasize the importance of earlier HIV diagnosis and presentation for care. This study evaluated the role of individual and community-level factors in late presentation to HIV care.

Methods: HIV-infected patients newly initiating outpatient HIV medical care at an academic medical center between 2005-2010 were included. Patients' self-reported addresses at their first clinic visit were geocoded using geographic information systems software to the appropriate United States census block group. Using …

The Reduction Of Central Line-Associated Bloodstream Infections In Intensive Care Units Through The Implementation Of The Comprehensive Unit-Based Safety Program, Michael Andrew Basinger

UNLV Theses, Dissertations, Professional Papers, and Capstones

Central line-associated bloodstream infections (CLABSIs) are one of the most significant healthcare-associated infections (HAIs) in the Intensive Care Unit (ICU) setting resulting in increased lengths of stay, increased healthcare costs, and higher mortality rates (Institute of Healthcare Improvement [IHI], 2012). Evidence that CLABSIs are largely preventable has created opportunities for healthcare organizations to implement evidence-based bloodstream infection prevention practices to reduce or eliminate these infections (Lissauer, Leekisa, Prease, Thom, & Johnson, 2012). Other efforts to reduce CLABSIs include implementation of safety programs to improve the safety culture in ICUs (Lissauer et al., 2012). One program, the comprehensive unit-based safety program …

Vaccinia Virus Flll Mediated Expedition Of Tanapoxvirus Replication In Cell Culture, Yih Wen Goh

Masters Theses

Tanapoxvirus (TPV) produces large but slow-forming plaques as opposed to vaccinia virus (VACV) that forms similar large plaques but more rapidly. A number of genes were identified in VACV, inclucding FllL, A33R, A34R and A36R that contribute to the regulation of virus release and dissemination, and are particularly responsible for the induction of actin tails. Among them, TPV lacks homologs of the FllL and A36R genes. F11Lmediated inhibition of RhoA-mDia signaling was shown to enhance the microtubules dynamics and modulates the cortical actin that assisted in the release of progeny virus from infected cells. To understand the possible effects of …

Hepatitis C Virus Infection Among Hiv-Positive Men Who Have Sex With Men: Protocol For A Systematic Review And Meta-Analysis, Holly Hagan, Joshua Neurer, Ashly E. Jordan, Don C. Des Jarlais, Jennifer Wu, Kirk Dombrowski, Bilal Khan, Ronald Scott Braithwaite, Jason Kessler

Publications and Research

Background: Outbreaks of hepatitis C virus (HCV) infection have been reported in HIV-positive men who have sex with men (MSM) in North America, Europe and Asia. Transmission is believed to be the result of exposure to blood during sexual contact. In those infected with HIV, acute HCV infection is more likely to become chronic, treatment for both HIV and HCV is more complicated and HCV disease progression may be accelerated. There is a need for systematic reviews and meta-analyses to synthesize the epidemiology, prevention and methods to control HCV infection in this population.

Methods/design: Eligible studies will include quantitative empirical …

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. De Groot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Dartmouth Scholarship

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which articular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing ‘agretopes'. Here we set out a new means of evaluating the …

Herpes Zoster Duplex Bilateralis, Sean Branch Do, Arthur C. Sosis Md, Stephen M. Purcell Do

Department of Medicine

No abstract provided.

Altering Murine Leukemia Virus Integration Through Disruption Of The Integrase And Bet Protein Family Interaction, Sriram Aiyer, G.V.T. Swapna, Nirav Malani, James M. Aramini, William M. Schneider, Matthew R. Plumb, Mustafa Ghanem, Ross C. Larue, Amit Sharma, Barbara Studamire, Mamuka Kvaratskhelia, Frederic D. Bushman, Gaetano T. Montelione, Monica J. Roth

Publications and Research

We report alterations to the murine leukemia virus (MLV) integrase (IN) protein that successfully result in decreasing its integration frequency at transcription start sites and CpG islands, thereby reducing the potential for insertional activation. The host bromo and extraterminal (BET) proteins Brd2, 3 and 4 interact with the MLV IN protein primarily through the BET protein ET domain. Using solution NMR, protein interaction studies, and next generation sequencing, we showthat the C-terminal tail peptide region ofMLV IN is important for the interaction with BET proteins and that disruption of this interaction through truncation mutations affects the global targeting profile of …

Molecular Pap Biomarkers For Cervical Cancer Risk Assessment In Thinprep® Clinical Specimens, Jennifer Taylor

Graduate School of Biomedical Sciences Theses and Dissertations

Approximately 500,000 patients are diagnosed with cervical cancer worldwide each year, thus making it the second most common cause of cancer-related deaths in women. Persistent high-risk human papillomavirus (HR-HPV) infections induce cervical dysplasia by increasing the expression of two viral oncogenes, E6 and E7. Utilization of the Papanicolaous smear test (Pap test) has contributed to a decrease in morbidity and mortality of cervical cancer; however, subjective analysis of cell morphology with a limited amount of cells has led to a substantial rate of false positive and false negative diagnoses. A more objective and sensitive diagnostic tool for the detection of …

Tobacco Use Among Adults Initiating Treatment For Hiv Infection In Rural Uganda, Gina R. Kruse, David Bangsberg, Judith A. Hahn, Jessica E. Haberer, Peter Hunt, Conrad Muzoora, John P. Bennett, Jeffrey N. Martin, Nancy A, Rigotti

OHSU-PSU School of Public Health Faculty Publications and Presentations

We conducted a longitudinal study of tobacco use among adults initiating antiretroviral therapy (ART) in Mbarara, Uganda where 11% of men and 3% of women use tobacco according to the 2011 Demographic and Health Survey. In a prospective cohort, self-reported tobacco use was assessed before starting ART and reassessed every 3–4 months. Plasma cotinine, a nicotine metabolite, was measured in a subset of adults pre-ART to verify self-report. Among 496 subjects, 50 (10%) reported current tobacco use (20% of men, 6% of women). Most (53%) adults with elevated cotinine levels (>15 ng/mL) reported no tobacco use. By 6 months …

The Differential Interferon Responses Of Two Strains Of Stat1-Deficient Mice Do Not Alter Susceptibility To Hsv-1 And Vsv In Vivo, Sarah Katzenell, Yufei Chen, Zachary M. Parker, David A. Leib

Dartmouth Scholarship

Stat1 is a pivotal transcription factor for generation of the interferon (IFN)-dependent antiviral response. Two Stat1 knockout mouse lines have been previously generated, one deleted the N-terminal domain (ΔNTD) and one in the DNA-binding domain (ΔDBD). These widely-used strains are assumed interchangeable, and both are highly susceptible to various pathogens. In this study, primary cells derived from ΔNTD mice were shown to be significantly more responsive to IFN, and established an antiviral state with greater efficiency than cells derived from ΔDBD mice, following infection with vesicular stomatitis virus and herpes simplex virus type-1. Also, while mice from both strains succumbed …

Vaccine-Preventable Diseases In Travelers, Edith Mirzaian, Jeffery A. Goad, Ani Amloian, Fady Makar

Pharmacy Faculty Articles and Research

Travel to the developing world is increasing among those from developed countries, placing them at risk for vaccine preventable and non-vaccine preventable diseases. From 2007-2011, the GeoSentinel Network reported 737 returned travelers with a vaccine preventable disease. While it is essential that clinicians use vaccines when available for a disease of risk, they should also be aware that the vast majority of diseases acquired by travelers are non-vaccine preventable. The vaccine preventable diseases can be divided into routine travel vaccines, special travel vaccines and routine vaccines used for travel. The routine travel vaccines include Hepatitis A and B, typhoid; special …

Impact Of Hiv On Cd8+ T Cell Cd57 Expression Is Distinct From That Of Cmv And Aging, Sulggi A. Lee, Elizabeth Sinclair, Hiroyu Hatano, Priscilla Y. Hsue, Lorrie Epling, Frederick M. Hecht, David Bangsberg, Jeffrey N. Martin, Joseph M. Mccune, Steven G. Deeks, Peter Hunt

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background: Chronic antigenic stimulation by cytomegalovirus (CMV) is thought to increase ‘‘immunosenesence’’ of aging, characterized by accumulation of terminally differentiated CD28- CD8+ T cells and increased CD57, a marker of proliferative history. Whether chronic HIV infection causes similar effects is currently unclear.

Methods: We compared markers of CD8+ T cell differentiation (e.g., CD28, CD27, CCR7, CD45RA) and CD57 expression on CD28- CD8+ T cells in healthy HIV-uninfected adults with and without CMV infection and in both untreated and antiretroviral therapy (ART)-suppressed HIV-infected adults with asymptomatic CMV infection.

Results: Compared to HIV-uninfected adults without CMV (n = 12), those with asymptomatic …

The Dynamic Relationship Between Social Support And Hiv-Related Stigma In Rural Uganda, Sae Takada, Sheri D. Weiser, Elias Kumbakumba, Conrad Muzoora, Jeffrey N. Martin, Peter Hunt, Jessica E. Haberer, Annet Kawuma, David Bangsberg, Alexander C. Tsai

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background—Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support.

Purpose—The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma.

Methods—We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma.

Results—Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and …

Phages Of Non-Diary Lactococci: Isolation And Characterization Of Phi L47, A Phage Infecting The Grass Isolate Lactococcus Lactis Ssp Cremoris Dpc6860, Daniel Cavanagh, Caitríona M. Guinane, Horst Neve, Aidan Coffey, R. Paul Ross, Gerald F. Fitzgerald, Olivia Mcauliffe

Department of Biological Sciences Publications

Lactococci isolated from non-dairy sources have been found to possess enhanced metabolic activity when compared to dairy strains. These capabilities may be harnessed through the use of these strains as starter or adjunct cultures to produce more diverse flavor profiles in cheese and other dairy products. To understand the interactions between these organisms and the phages that infect them, a number of phages were isolated against lactococcal strains of non-dairy origin. One such phage, ΦL47, was isolated from a sewage sample using the grass isolate L. lactis ssp. cremoris DPC6860 as a host. Visualization of phage virions by transmission electron …