Medical Immunology Commons^™

High Prevalence Of Early Childhood Infection By Kshv In A Minority Population In China, Yifei Cao, Veenu Minhas, Xiaohua Tan, Jin Huang, Baodong Wang, Meiyi Zhu, Yuan Gao, Tingting Zhao, Lei Yang, Charles Wood

Nebraska Center for Virology: Faculty Publications

In China, KSHV seroprevalence varies considerably among different regions and ethnicities. But in Xinjiang province, located in the northwestern China, there is a very high seroprevalence of KSHV in adults of Kazak and Ughur ethnicities. However, KSHV prevalence in children and the risk factors associated with the acquisition of infection are currently not known. The aim of this study was to investigate the prevalence of KSHV infection, identify associated socio-economic or behavioral risk factors and the humoral immune response among children in this population. This is a cross-sectional study (N=178) to screen children and their caregivers from Xinjiang for total …

Global Analysis Of Chlorella Variabilis Nc64a Mrna Profiles During The Early Phase Of Paramecium Bursaria Chlorella Virus-1 Infection, Janet M. Rowe, Adrien Jeanniard, James R. Gurnon, Yuannan Xia, David D. Dunigan, James L. Van Etten, Guillaume Blanc

Nebraska Center for Virology: Faculty Publications

The PBCV-1/Chlorella variabilis NC64A system is a model for studies on interactions between viruses and algae. Here we present the first global analyses of algal host transcripts during the early stages of infection, prior to virus replication. During the course of the experiment stretching over 1 hour, about a third of the host genes displayed significant changes in normalized mRNA abundance that either increased or decreased compared to uninfected levels. The population of genes with significant transcriptional changes gradually increased until stabilizing at 40 minutes post infection. Functional categories including cytoplasmic ribosomal proteins, jasmonic acid biosynthesis and anaphase promoting …

Dynamic Attachment Of Chlorovirus Pbcv-1 To Chlorella Variabilis, Irina Agarkova, Brigitte Hertel, Xinzheng Zhang, Les Lane, Alexander Tchourbanov, David D. Dunigan, Gerhard Thiel, Michael G. Rossmann, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Chloroviruses infect their hosts by specifically binding to and degrading the cell wall of their algal hosts at the site of attachment, using an intrinsic digesting enzyme(s). Chlorovirus PBCV-1 stored as a lysate survived longer than virus alone, suggesting virus attachment to cellular debris may be reversible. Ghost cells (algal cells extracted with methanol) were used as a model to study reversibility of PBCV-1 attachment because ghost cells are as susceptible to attachment and wall digestion as are live cells. Reversibility of attachment to ghost cells was examined by releasing attached virions with a cell wall degrading enzyme extract. The …

Genetic Variation And Possible Mechanisms Driving The Evolution Of Worldwide Fig Mosaic Virus Isolates, Jeewan Jyot Walia, Anouk Willemsen, Eminur Elci, Kadriye Caglayan, Bryce W. Falk, Luis Rubio

Nebraska Center for Virology: Faculty Publications

Fig mosaic virus (FMV) is a multipartite negative-sense RNA virus infecting fig trees worldwide. FMV is transmitted by vegetative propagation and grafting of plant materials, and by the eriophyid mite Aceria ficus. In this work, the genetic variation and evolutionary mechanisms shaping FMV populations were characterized. Nucleotide sequences from four genomic regions (each within the genomic RNAs 1, 2, 3, and 4) from FMV isolates from different countries were determined and analyzed. FMV genetic variation was low, as is seen for many other plant viruses. Phylogenetic analysis showed some geographically distant FMV isolates which clustered together, suggesting long-distance migration. …

Risk Factors For Early Childhood Infection Of Human Herpesvirus-8 In Zambian Children: The Role Of Early Childhood Feeding Practices, Kay L. Crabtree, Janet M. Wojcicki, Veenu Minhas, David R. Smith, Chipepo Kankasa, Charles D. Mitchell, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background—Human herpesvirus-8 (HHV-8) infection in early childhood is common throughout sub-Saharan Africa with prevalence increasing throughout childhood. Specific routes of transmission have not been clearly delineated, though HHV-8 is present in high concentrations in saliva.

Methods—To understand the horizontal transmission of HHV-8 within households to children we enrolled for cross-sectional analysis, 251 households including 254 children, age two and under, in Lusaka, Zambia. For all children, plasma was screened for HHV-8 and HIV-1 and health and behavioral questionnaires were completed. Multi-level logistic regression analysis was conducted to assess independent factors for HHV-8 infection in children.

Results—Risk factors for HHV-8 infection …

Turnip Crinkle Virus Coat Protein Inhibits The Basal Immune Response To Virus Invasion In Arabidopsis By Binding To The Nac Transcription Factor Tip, Teresa Donze, Feng Qu, Paul Twigg, T. Jack Morris

Nebraska Center for Virology: Faculty Publications

Turnip crinkle virus (TCV) has been shown to interact with a NAC transcription factor, TIP, of Arabidopsis thaliana, via its coat protein (CP). This interaction correlates with the resistance response manifested in TCV-resistant Arabidopsis ecotype Di-17. We report that failure of a mutated CP to interact with TIP triggered the corresponding TCV mutant (R6A) to cause more severe symptoms in the TCV-susceptible ecotype Col-0. We hypothesized that TCV regulates antiviral basal immunity through TIP-CP interaction. Consistent with this hypothesis, we found that the rate of accumulation of R6A was measurably slower than wild-type TCV over the course of an …

The Role Of Scavenger Receptor Class B Type I-Regulated Inducible Glucocorticoids In Sepsis, Junting Ai

Theses and Dissertations--Nutritional Sciences

Sepsis claims over 215,000 lives in the US annually. Inducible glucocorticoids (iGC) is produced during sepsis. However, the precise effects of iGC in sepsis remain unclear due to a lack of appropriate animal models. Glucocorticoid (GC) insufficiency is associated with a marked increase in mortality and occurs in 60% of severe septic patients. Yet the conclusion of GC therapy on septic patients is still controversial.

Scavenger receptor class B type I (SR-BI) in the adrenal mediates the selective uptake of cholesteryl ester from lipoproteins for GC synthesis. SR-BI-/- mice completely lack iGC during sepsis and are highly susceptible to septic …

Cyclic Peptide-Capped Gold Nanoparticles For Enhanced Sirna Delivery, Amir Nasrolahi Shirazi, Karissa L. Paquin, Niall G. Howlett, Dindyal Mandal, Keykavous Parang

Pharmacy Faculty Articles and Research

Previously, we have reported the synthesis of a homochiral L-cyclic peptide [WR]5 and its use for delivery of anti-HIV drugs and biomolecules. A physical mixture of HAuCl4 and the peptide generated peptide-capped gold nanoparticles. Here, [WR]5 and [WR]5-AuNPs were tested for their efficiency to deliver a small interfering RNA molecule (siRNA) in human cervix adenocarcinoma (HeLa) cells. Flow cytometry investigation revealed that the intracellular uptake of a fluorescence-labeled non-targeting siRNA (200 nM) was enhanced in the presence of [WR]5 and [WR]5-AuNPs by 2- and 3.8-fold when compared with that of siRNA alone after 24 h incubation. Comparative toxicity results showed …

Induction Of A Type I Interferon Signature In Normal Human Monocytes By Gadolinium-Based Contrast Agents: Comparison Of Linear And Macrocyclic Agents., Peter J. Wermuth, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between …

Increased Incidence Of Asthma After Previous Infantile Rsv Bronchiolitis Infection, Ellen Adelia Doebler

Physician Assistant Scholarly Project Posters

• Respiratory Syncytial Virus (RSV) is a very common infection in children less than two years of age.

• Asthma is a common respiratory disease in childhood, which may cause frequent hospitalizations.

• The purpose of this study is to determine if infants previously diagnosed with RSV bronchiolitis have an increased incidence of asthma diagnosis compared to infants not diagnosed with RSV.

• The literature review examines correlation studies of both disease processes and explores incidence of asthma in patients previously diagnosed with Respiratory Syncytial Virus bronchiolitis.

• Individuals previously diagnosed with Respiratory Syncytial Virus bronchiolitis have a higher risk …

Immunotherapy As A Treatment Option For Patients With Pancreatic Cancer, Yehuda Lehrfield

The Science Journal of the Lander College of Arts and Sciences

Pancreatic cancer is one of the worst forms of cancer that can develop in an individual. Traditionally, chemotherapy is administered but it has very limited success. Using the immune system to treat the cancer is very enticing and many studies have been conducted to attempt to harness the body’s own mechanisms to defeat the cancer. It seems that in order to properly treat the tumor a two pronged approach must be used. First, the immune system must be stimulated to react to the tumor and attack it. A possible cytokine that can be utilized is interferon alpha, which could result …

Efficient B Cell Responses To Borrelia Hermsii Infection Depend On Baff And Baffr But Not Taci., Gregory S. Dickinson, Phd, Guizhi Sun, Richard J Bram, Kishore Alugupalli

Department of Microbiology and Immunology Faculty Papers

T cell-independent antibody responses develop rapidly, within 3 to 4 days, and are critical for preventing blood-borne pathogens from evolving into life-threatening infections. The interaction of BAFF, also known as BLyS, with its receptors BAFFR and TACI on B cells is critical for B cell homeostasis and function. Using a synthetic polysaccharide antigen, it has previously been shown that TACI is critical for T cell-independent antibody responses. To examine the role of BAFFR and TACI in T cell-independent antibody responses to an active infection, we utilized the Borrelia hermsii infection system. In this infection system, T cell-independent responses mediated by …

Cell- And Virus-Mediated Regulation Of The Barrier-To-Autointegration Factor’S Phosphorylation State Controls Its Dna Binding, Dimerization, Subcellular Localization, And Antipoxviral Activity, Augusta Jamin, April Wicklund, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Barrier-to-autointegration factor (BAF) is a DNA binding protein with multiple cellular functions, including the ability to act as a potent defense against vaccinia virus infection. This antiviral function involves BAF’s ability to condense double-stranded DNA and subsequently prevent viral DNA replication. In recent years, it has become increasingly evident that dynamic phosphorylation involving the vaccinia virus B1 kinase and cellular enzymes is likely a key regulator of multiple BAF functions; however, the precise mechanisms are poorly understood. Here we analyzed how phosphorylation impacts BAF’s DNA binding, subcellular localization, dimerization, and antipoxviral activity through the characterization of BAF phosphomimetic and unphosphorylatable …

Characterization Of A Dual-Tropic Human Immunodeficiency Virus (Hiv-1) Strain Derived From The Prototypical X4 Isolate Hxbc2, Shi-Hua Xiang, Beatriz Pacheco, Dane Bowder, Wen Yuan, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) coreceptor usage and tropism can be modulated by the V3 loop sequence of the gp120 exterior envelope glycoprotein. For coreceptors, R5 viruses use CCR5, X4 viruses use CXCR4, and dual-tropic (R5X4) viruses use either CCR5 or CXCR4. To understand the requirements for dual tropism, we derived and analyzed a dual-tropic variant of an X4 virus. Changes in the V3 base, which allow gp120 to interact with the tyrosine-sulfated CCR5 N-terminus, and deletion of residues 310/311 in the V3 tip were necessary for efficient CCR5 binding and utilization. Thus, both sets of V3 changes allowed …

Live Siv Vaccine Correlate Of Protection: Immune Complex-Inhibitory Fc Receptor Interactions That Reduce Target Cell Availability, Anthony J. Smith, Stephen W. Wietgrefe, Liang Shang, Cavan S. Reilly, Peter J. Southern, Katherine E. Perkey, Lijie Duan, Heinz Kohler, Sybille Muller, James Robinson, John V. Carlis, Qingsheng Li, R. Paul Johnson, Ashley T. Haase

Nebraska Center for Virology: Faculty Publications

Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to

protect women in the pandemic’s epicentre in Africa. We have been seeking these principles by

identifying correlates of the robust protection associated with SIV_mac239Δnef vaccination in the

SIV-rhesus macaque animal model of HIV-1 transmission to women. We have identified one

correlate of SIV_mac239Δnef protection against vaginal challenge as a resident mucosal system for

SIV-gp41 trimer antibody production and neonatal Fc receptor (FcRn)-mediated concentration of

these antibodies on the path of virus entry to inhibit establishment of infected founder populations

at the …

Review Of Epidemiology And Transmission Of Kaposi’S Sarcoma-Associated Herpesvirus, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

This review summarizes the current knowledge pertaining to Kaposi sarcoma-associated herpesvirus (KSHV) epidemiology and transmission. Since the identification of KSHV twenty years ago, it is now known to be associated with Kaposi’s sarcoma (KS), primary effusion lymphoma, and multicentric Castleman’s disease. Many studies have been conducted to understand its epidemiology and pathogenesis and their results clearly show that the worldwide distribution of KSHV is uneven. Some geographical areas, such as sub-Saharan Africa, the Mediterranean region and the Xinjiang region of China, are endemic areas, but Western Europe and United States have a low prevalence in the general population. This makes …

Seroprevalence Of Human Herpesvirus 8 And Hepatitis C Virus Among Drug Users In Shanghai, China, Tiejun Zhang, Ying Liu, Yuyan Zhang, Jun Wang, Veenu Minhas, Charles Wood, Na He

Nebraska Center for Virology: Faculty Publications

To elucidate and compare the seroprevalence of human herpesvirus 8 (HHV8) and hepatitis C virus (HCV) among Chinese drug users, a cross-sectional study of 441 participants, was conducted in Shanghai, China, from 2012 through 2013. Seventy-seven (17.5%) participants were found to be positive for HHV8 antibodies, while 271 (61.5%) participants were positive for HCV. No significant association between HHV8 seropositivity and drug use characteristics, sexual behaviors, HCV, or syphilis was observed. In contrast, a statistically significant association between HCV seropositivity and injected drug history (OR, 2.18, 95% CI 1.41–3.37) was detected, whereas no statistically significant association between HCV seropositivity and …

Vaccines Within Vaccines: The Use Of Adenovirus Types 4 And 7 As Influenza Vaccine Vectors, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

adenovirus Types 4 and 7 (ad4 and ad7) are associated with acute respiratory distress (aRD). In order to prevent wide- spread ad-associated aRD (ad-aRD) the United states military immunizes new recruits using a safe and effective lyophi- lized wildtype ad4 and ad7 delivered orally in an enteric-coated capsule. We cloned ad4 and ad7 and modified them to express either a GFP-Luciferase (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (Ha1-con). BaLB/c mice were injected with GFPLuc expressing viruses intramuscularly (i.m.) and intranasally (i.n.). ad4 induced significantly higher luciferase expression levels as compared with ad7 by both routes. ad7 transduction …

Comparison Of Two Different Sprint Interval Training Work-To-Rest Ratios On Acute Metabolic And Inflammatory Responses, Christopher R. Harnish

Theses and Dissertations

High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only do high-intensity interval training (HIT) and sprint interval training (SIT) produce significant improvements in cardiovascular fitness and disease, they may be more effective at improving long-term metabolic function, including insulin sensitivity (Si), by producing more mitochondria. Moreover, compliance rates for HIT and SIT participation are reported to be the same or better than traditional moderate intensity exercise. Because lack of time is often cited as major hindrance to exercise participation, SIT is also seen as a …

Analysis Of The Role Of Astrocyte Elevated Gene-1 In Normal Liver Physiology And In The Onset And Progression Of Hepatocellular Carcinoma, Chadia L. Robertson

Theses and Dissertations

First identified over a decade ago, Astrocyte Elevated Gene-1 (AEG-1) has been studied extensively due to early reports of its overexpression in various cancer cell lines. Research groups all over the globe including our own have since identified AEG-1 overexpression in cancers of diverse lineages including cancers of the liver, colon, skin, prostate, breast, lung, esophagus, neurons and neuronal glia as compared to matched normal tissue. A comprehensive and convincing body of data currently points to AEG-1 as an essential component, critical to the progression and perhaps onset of cancer. AEG-1 is a potent activator of multiple pro-tumorigenic signal transduction …

Heterogeneous Immunological Landscapes And Medieval Plague : An Invitation To A New Dialogue Between Historians And Immunologists., Fabian Crespo, Matthew B. Lawrenz

Faculty and Staff Scholarship

Efforts to understand the differential mortality caused by plague must account for many factors, including human immune responses. In this essay we are particularly interested in those people who were exposed to the Yersinia pestis pathogen during the Black Death, but who had differing fates—survival or death—that could depend on which individuals (once infected) were able to mount an appropriate immune response as a result of biological, environmental, and social factors. The proposed model suggests that historians of the medieval world could make a significant contribution to the study of human health, and especially the role of human immunology in …

Characterization Of Complement Evasion Of The Periopathogen, Treponema Denticola, Daniel Patrick Miller

Theses and Dissertations

Periodontitis is a polymicrobially-induced, chronic inflammatory disease of the tissues that support and surround the tooth. While greater than 500 organisms are found in dental plaque, Treponema denticola is one of only a few species associated with disease. It has been hypothesized that oral bacteria disrupt host homeostasis through manipulation of the innate immune system. In this study, we examine the impact of binding and subsequent cleavage of factor H, a complement regulator, by T. denticola in the evasion and subversion of complement. The molecular interaction between the sole FH-binding protein, FhbB, and FH was detailed by x-ray crystallography, site-directed …

Transformation Of Human Mast Cells By Interferon-Gamma And The Potential Role Of Myeloid Derived Suppressor Cells In Mastocytosis., Sahar Lotfi-Emran

Theses and Dissertations

Mast cells respond to a variety of signals, are associated with both increased inflammation and regulation of the immune response, and are able to interact with a variety of hematopoietic and non-hematopoietic cells. The majority of the work that highlights mast cell pleiotropic abilities has been completed in murine models. Though these models have significantly advanced our understanding of what mast cells can do, they cannot inform us as to what mast cells actually do in human beings. The goal of this dissertation is to assess fully mature, primary human mast cell function beyond the well-defined type 1 hypersensitivity function …

Importance Of Bacillithiol In The Oxidative Stress Response Of Staphylococcus Aureus, Ana C. Posada, Stacey L. Kolar, Renata G. Dusi, Patrica Francois

Dartmouth Scholarship

In Staphylococcus aureus, the low-molecular-weight thiol called bacillithiol (BSH), together with cognate S-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH in S. aureus, we constructed mutants with the deletion of bshA (sa1291), which encodes the glycosyltransferase that catalyzes the first step of BSH biosynthesis, and fosB (sa2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in several S. aureus strains, including clinical isolates. Mutation of fosB or bshA caused a 16- to 60-fold reduction in fosfomycin resistance in these S. aureus strains. High-pressure liquid chromatography analysis, which …