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Whole-Genome Sequencing Of Kaposi’S Sarcoma-Associated Herpesvirus From Zambian Kaposi’S Sarcoma Biopsy Specimens Reveals Unique Viral Diversity, Landon Olp, Adrien Jeanniard, Clemence Marimo, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi’s sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries—where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap since it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment …

Observed And Expected Incidence Of Cervical Cancer In Lusaka And The Southern And Western Provinces Of Zambia, 2007 - 2012, Mulele Kalima, Kennedy Lishimpi, Jane L. Meza, Shinobu Watanabe-Galloway, Susan C. Msadabwe, Catherine K. Mwaba, Aaron L. Shibemba, Lewis Banda, Charles Wood, Robert M. Chamberlain, Amr S. Soliman

Nebraska Center for Virology: Faculty Publications

Objectives—Cervical cancer is increasing but underestimated in developing countries. We calculated the observed and expected incidence of cervical cancer in Lusaka and Southern and Western provinces of Zambia.

Methods/Materials—Data for 2007-2012 was obtained for the 3 provinces. Data included age, residence, year of diagnosis, marital status, occupation, HIV, stage, radiotherapy and chemotherapy. Expected incidence in Southern and Western provinces was calculated based on observed incidence for Lusaka province, adjusting for HIV.

Results—Crude and age-standardized incidence rates (ASR) in Lusaka were 2-4 times higher than incidence in the other 2 provinces. Lusaka had a rate of 54.1/10⁵ and ASR of …

Crf07_Bc Strain Dominates The Hiv-1 Epidemic In Injection Drug Users In Liangshan Prefecture Of Sichuan, China, Lin Li, Daying Wei, Wan-Ling Hsu, Tianyi Li, Tao Gui, Charles Wood, Yongjian Liu, Hanping Li, Zuoyi Bao, Siyang Liu, Xiaolin Wang, Jingyun Li

Nebraska Center for Virology: Faculty Publications

The Liangshan prefecture in Sichuan province is an area in China severely affected by the HIV epidemic, with intravenous drug use (IDU) as the main risk factor. No reports on HIV subtypes prevalent in IDUs in Liangshan prefecture could be found. In this study, we have characterized the genotypes of HIV-1 in the IDU population in Liangshan prefecture and further determined the phylogenetic relationship of the CRF07_BC strains to HIV-1 sequences from the other regions of China, including Xinjiang and Yunnan provinces, to explore the pattern and possible diffusion pathway of HIV-1 in these regions. HIV-1-seropositive drug-naive IDUs identified in …

Effects On Quinolone Resistance Due To The Biofilm Formation Activity In Ureaplasma Urealyticum, Chunyan Feng, Ya Huang, Yunsong Yu, Guorong Duan, Yuying Dai, Ke Dong, Qingtian Li

Turkish Journal of Medical Sciences

To detect the effects on quinolone resistance due to biofilm formation activity in Ureaplasma urealyticum. Materials and methods: An improved checkerboard dilution susceptibility test was used to analyze the quinolone resistance of clinical Ureaplasma isolates and a postbiofilm formation susceptibility assay was used to compare the effects on the quinolone susceptibility between pre- and postbiofilm formations. Several important functional gene expressions were detected to evaluate their roles in the process of the quinolone resistance mechanism. Results: The quinolone-resistant isolates produced more biofilms than the sensitive isolates. In both the quinolone-resistant and -sensitive groups, the minimal inhibitory concentrations after biofilm formation …

Distribution Of Viral Genotypes And Extrahepatic Manifestations In Patients With Chronic Hepatitis C In Eastern Turkey, Si̇bel İba Yilmaz, Serpi̇l Erol, Ahmet Özbek, Mehmet Parlak

Turkish Journal of Medical Sciences

To investigate the distribution of viral genotypes, the extrahepatic manifestations, and the relationship between genotypes and extrahepatic manifestations in patients with chronic hepatitis C. Materials and methods: The study included 62 treatment-naive patients with chronic hepatitis C infection. Genotype determination was performed by DNA sequencing analysis. To investigate extrahepatic manifestations, the patients' data, recorded prospectively during the pretreatment period, were analyzed. Results: Genotype determination was successful in 74.2% of the cases. All patients were infected with hepatitis C virus (HCV) genotype 1b. At least 1 extrahepatic manifestation was identified in 37.1% of the patients. The most frequent clinical manifestations were …

Prognostic Value Of Hemostasis-Related Parameters For Prediction Of Organ Dysfunction And Mortality In Sepsis, Dunja Mihajlovic, Dajana Lendak, Gorana Mitic, Tatjana Cebovic, Biljana Draskovic, Aleksandra Novakov, Snezana Brkic

Turkish Journal of Medical Sciences

Clinical manifestations of sepsis are not caused directly by the invading pathogens, but rather mostly by systemic inflammation that leads to activation of the coagulation system. The aim of this study was to determine whether levels of hemostasis-related parameters measured in intensive care unit admissions are associated with mortality and severity in patients with sepsis. Materials and methods: Eighty-five patients who fulfilled criteria for a diagnosis of sepsis were included in our study. Platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time, D-dimer, and fibrinogen levels were determined within the first 24 h from sepsis onset. Differences …

The Relationship Between Hepatitis Serology Of Ambulance Attendants Andduration Of Education, Ertuğrul Güçlü, Azi̇z Öğütlü, Oğuz Karabay

Turkish Journal of Medical Sciences

Background/aim: Healthcare workers (HCWs) run the risk of hepatitis B virus (HBV) infection. Studies investigating the HBV and hepatitis C virus (HCV) serology of HCWs have been generally conducted in secondary or tertiary hospitals. In this study we aimed to determine the relationships between education level and HBV and HCV serology and HBV vaccination status of ambulance attendants. Materials and methods: The data of this study were obtained by retrospective review of ambulance personnel files in Sakarya Province, Turkey. Results: Out of 314 ambulance attendants, 216 (68.7%; 78 males, 138 females) were enrolled in this study. The mean length of …

Clinical Characteristics Of 75 Pandemic H1n1 Influenza Patientsfrom Turkey; Risk Factors For Fatality, Hati̇ce Kiliç, Asi̇ye Kanbay, Ayşegül Karalezli̇, Hati̇ce Canan Hasanoğlu, Can Ateş

Turkish Journal of Medical Sciences

Background/aim: The 2009 influenza A (H1N1) pandemic caused mild to severe illnesses and led to death in some cases. In this study, we aimed to evaluate the relationship between the serum D-dimer levels, CURB-65 scores, and the severity of pneumonia among patients with H1N1 infections. Materials and methods: Sixty-eight patients who had probable H1N1 infections were evaluated by clinical, radiological, and laboratory methods. The H1N1 strain was specified by reverse transcription-polymerase chain reaction. Of 55 patients diagnosed with pneumonia, 18 exhibited H1N1 positivity and 37 patients did not. Results: CURB-65 scores of pneumonia patients with H1N1 (group 1) were higher …

Elevated Serum Matrix Metalloproteinase-2 And -9 And Their Correlationswith Severity Of Disease In Patients With Community-Acquired Pneumonia, Haci Ahmet Bi̇rcan, Müni̇re Çakir, İlkay Yilmazer Kapulu, Recep Sütcü, Selçuk Kaya, Önder Öztürk

Turkish Journal of Medical Sciences

Background/aim: To determine the role of matrix metalloproteinases (MMPs) and their relationship with the clinical course of community-acquired pneumonia (CAP). Materials and methods: Sixty-two consecutively hospitalized patients with CAP were enrolled and their pneumonia severity index (PSI), time to clinical stability (TCS), treatment response, and complications were recorded. The pre- and posttreatment serum concentrations of MMPs and their inhibitors were analyzed by ELISA. The activities of MMPs were evaluated by gelatin zymography. Results: MMP-2 and -9 serum levels and their activities were higher in CAP patients than controls (P < 0.001 and P < 0.001, respectively). Low-risk patients had lower levels of MMP-2 and TIMP-1 than high-risk patients (P = 0.044, P = 0.001, respectively). Pretreatment serum TIMP-1 level was higher in patients with TCS of >3 days (P = 0.004) and was correlated with oxygenation and …

Distribution And Antifungal Resistance Of Candida Speciesisolated From Intensive Care Units, Pinar Korkmaz, Yeşi̇m Alpay, Fi̇gen Çevi̇k, Nevi̇l Aykin, Ayşe Koygun, Hakki Mustafa Güldüren

Turkish Journal of Medical Sciences

No abstract provided.

Acute Tuberculosis In The Intensive Care Unit, Kazim Rollas, Ati̇la Kara, Nazmi̇ye Ebru Ortaç Ersoy, Kezban Özmen Süner, Mehmet Nezi̇r Güllü, Serpi̇l Öcal, Arzu Topeli̇

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to determine mortality rates and to evaluate clinical features of patients with active tuberculosis (TB) requiring intensive care unit (ICU) admission. Materials and methods: The medical records of active TB patients requiring ICU admission were retrospectively reviewed over a 5-year period. Results: Sixteen patients with active TB admitted to the ICU were included in the study. Seven (43.8%) patients died in the ICU. The cause of mortality was septic shock in 5 patients and respiratory failure in 2 patients. The Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure …

Role Of Autophagy In The Pathogenesis Of Alzheimer Disease, Muhammet Cemal Kizilarslanoğlu, Zekeri̇ya Ülger

Turkish Journal of Medical Sciences

Alzheimer disease (AD) is the most common progressive neurodegenerative disorder causing increased morbidity and mortality. It is characterized by accumulation of amyloid-β in neurons. As there is no known definitive treatment of this disorder, studies trying to determine its exact pathogenetic pathways and target therapies for these specific pathways are being rapidly conducted. Autophagy is one of the areas of interest in studies on the pathogenesis of AD. It is a process of self-digestion that is thought to be a response to stressors and allows cells to adapt to environmental changes. There is accumulating evidence showing an association between autophagy …

Assessment Of Bloodstream Infections And Risk Factors In An Intensive Care Unit, Aynur Süner, İlkay Karaoğlan, Ayşe Özlem Mete, Mustafa Namiduru, Vuslat Boşnak, İbrahi̇m Baydar

Turkish Journal of Medical Sciences

Background/aim: Nosocomial bloodstream infection (BSI) increases mortality rates, duration of stay in hospital, and treatment costs. This study was conducted to determine the rate and the risk factors of BSIs among intensive care unit patients. Materials and methods: Sixty-four patients with BSIs (patient group) and 79 patients without a nosocomial infection (control group) were enrolled in the study. Centers for Disease Control and Prevention criteria were used for diagnosing BSIs. Potential risk factors were evaluated by multivariate logistic regression model. Results: The BSI development rate was 15.7% (64/407), with an incidence rate of 18.2/1000 patient days. Distribution of pathogens among …

Applicability Of Xpert Mtb/Rif Assay For Routine Diagnosis Of Tuberculosis: A Four-Year Single-Center Experience, Cem Çeli̇k, Mustafa Gökhan Gözel, Mustafa Zahi̇r Bakici, Serdar Berk, Sefa Levent Özşahi̇n, Esra Gültürk

Turkish Journal of Medical Sciences

Background/aim: The aim of this study is to assess the Xpert MTB/RIF assay for diagnosis of the Mycobacterium tuberculosis complex in clinical samples and to compare the results by reference to the diagnostic method, Bactec MGIT 960. Materials and methods: A total of 7407 samples were included from patients not primarily suggesting pulmonary or extrapulmonary tuberculosis (TB), collected from patients required to be screened for TB and excluding TB diagnoses since it was a differential diagnosis. Also included were a total of 411 samples from patients primarily suggesting pulmonary or extrapulmonary TB. Results: In the first group, 152 of 7407 …

The Effects Of Vitamin D Supplementation On Influenza, Jonah M. Spoerndle

Williams Honors College, Honors Research Projects

Recently the role of vitamin D in other non-classical capacities has been evaluated. One of these non-classical vitamin D roles is assisting in maintaining proper immune system health. One disease that has a great effect on the immune system is influenza. Vitamin D helps to prevent and limit influenza by moderating the inflammatory cytokines as well as promoting the production of monocytes that help destroy the invading materials. Through the use of vitamin D supplementation the recommended daily amount of vitamin D can be assured and optimal health could be achieved. The purpose of this project was to design a …

Mucocutaneous Manifestations And The Relationship To Cd4 Lymphocyte Counts Among Turkish Hiv/Aids Patients In İstanbul, Turkey, Özlem Altuntaş Aydin, Hayat Kumbasar Karaosmanoğlu, Ramazan Korkusuz, Mehmet Özeren, Özcan Nazlican

Turkish Journal of Medical Sciences

Dermatologic findings differ among countries but no sufficient data about Turkish HIV-infected patients exist in the literature. Therefore, our aim in this study was to document the dermatologic manifestations and their relationships with CD4 cell counts among HIV/AIDS patients visiting our clinic for the first time in İstanbul, Turkey. Materials and methods: A retrospective analysis of 306 HIV/AIDS patients (260 men, mean age: 38.3 years) was done in a tertiary hospital in İstanbul from January 2006 to September 2012. Information on age, sex, transmission routes, socioeconomic and educational status, CD4 counts, and dermatologic findings was collected retrospectively from medical records. …

Relationship Among Mif, Mcp-1, Viral Loads, And Hbs Ag Levelsin Chronic Hepatitis B Patients, Hayati̇ Güneş, Rafet Mete, Murat Aydin, Bi̇rol Topçu, Mustafa Oran, Mustafa Doğan, Oğuzhan Yildirim, İlknur Erdem, Aynur Eren Topkaya, Ahmet Gürel

Turkish Journal of Medical Sciences

Background/aim: To determine whether macrophage migration inhibitory factor (MIF) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with hepatitis B (HB) are different than in normal individuals and whether the HB surface antigen (HBs Ag) level and viral load are correlated with each other and with the two aforementioned parameters. Materials and methods: Sera were obtained from 52 chronic active HB (CAHB) patients and 33 healthy controls, and their MIF and MCP-1 levels were measured. Statistical analyses were performed. A value of P < 0.05 was considered statistically significant. Results: The MIF and MCP-1 values of the control group were increased compared to those of the CAHB group. The MIF and MCP-1 levels were negatively correlated with HBs Ag levels and viral loads. The MIF and MCP-1 levels were positively correlated. The HBs Ag levels and the log10 of the viral loads were positively correlated. Conclusion: We conclude that the negative correlation of MIF and MCP-1 with viral load and HBs Ag levels may be due to T-cell deficiency, antinuclear antibody seropositivity, and/or inhibition of chemokine ligand 2 receptors by viral antigens. More studies with a greater number of subjects are needed to evaluate the potential role of MIF and MCP in CAHB.

The Effect Of Statins On Il-33 Mediated Mast Cell Function, Marcela Taruselli

Theses and Dissertations

This study demonstrates original findings of statin effects on IL-33 stimulated mast cells. Statins are a class of drugs used to lower cholesterol production by targeting HMG CoA reductase. These commonly prescribed drugs have been shown to be immunomodulatory. In this study, we have found that pretreatment with statins has a variety of effects on IL-33 stimulated mast cells. Atorvastatin suppresses TNF and IL-6 production, while fluvastatin significantly enhances release of these proinflammatory cytokines in BMMCs. Although they have differing effects on cytokine production, both statins lowered ST2 expression on the cell surface, decreased cell viability, and enhanced expression of …

Rhabdovirus-Based Vaccine Platforms Against Henipaviruses., Drishya Kurup, Christoph Wirblich, Heinz Feldmann, Andrea Marzi, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: The emerging zoonotic pathogens Hendra virus (HeV) and Nipah virus (NiV) are in the genus Henipavirus in the family Paramyxoviridae. HeV and NiV infections can be highly fatal to humans and livestock. The goal of this study was to develop candidate vaccines against henipaviruses utilizing two well-established rhabdoviral vaccine vector platforms, recombinant rabies virus (RABV) and recombinant vesicular stomatitis virus (VSV), expressing either the codon-optimized or the wild-type (wt) HeV glycoprotein (G) gene. The RABV vector expressing the codon-optimized HeV G showed a 2- to 3-fold increase in incorporation compared to the RABV vector expressing wt HeV G. There …

Characterization Of Cd8+ T Cell Differentiation Following Sivδnef Vaccination By Transcription Factor Expression Profiling, James M. Billingsley, Premeela A. Rajakumar, Michelle A. Connole, Nadine C. Salisch, Sama Adnan, Yury V. Kuzmichev, Henoch S. Hong, R. Keith Reeves, Hyung-Joo Kang, Wenjun Li, Qingsheng Li, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8⁺ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8+⁺ T cells, and in SIV-specific CD8⁺ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8⁺ T cells into groups concordant with cell surface phenotype. Transcription factor …

Escherichia Coli Surface Display Of Single-Chain Antibody Vrc01 Against Hiv-1 Infection, Lin-Xu Wang, Michael Mellon, Dane Bowder, Meghan Quinn, Danielle Shea, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from …

Evidence For Placental Hpv Infection In Both Hiv Positive And Negative Women, Chrispin Chisanga, Dawn Eggert, Charles D. Mitchell, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Human papillomaviruses (HPVs) have previously been reported to infect epithelial trophoblast cells of the placenta. To investigate this possibility, 200 placental samples from Zambian women were separated into HIV+ and HIV− groups and tested for HPV by redundant primer PCR, using GP5+/GP6+ and CPI/CPII primer sets. Three HPV genotypes (HPV6, 16 and 90) were detected in placental samples. Whereas, 20 different HPV genotypes were detected in vaginal sampling of the same patients, suggesting that compartment specific sub-populations of HPV may exist. The incidence of HPV16 in placental samples was almost 2-fold greater in HIV+ women compared to HIV− (p = …

The Hippo/Yap Pathway Interacts With Egfr Signaling And Hpv Oncoproteins To Regulate Cervical Cancer Progression, Chunbo He, Dagan Mao, Guohua Hua, Xiangmin Lv, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Steven W. Remmenga, Kerry J. Rodabaugh, Jin Zhou, Paul F. Lambert, Peixin Yang, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

The Hippo signaling pathway controls organ size and tumorigenesis

through a kinase cascade that inactivates Yes-associated

protein (YAP). Here, we show that YAP plays a central role in

controlling the progression of cervical cancer. Our results suggest

that YAP expression is associated with a poor prognosis for cervical

cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo

signaling pathway and activate YAP to induce cervical cancer cell

proliferation and migration. Activated YAP allows for up-regulation

of TGF-α, AREG, and EGFR, forming a positive signaling loop to

drive cervical cancer cell proliferation. HPV E6 protein, a major

etiological molecule of …

Kaposi’S Sarcoma At The University Teaching Hospital, Lusaka, Zambia In The Antiretroviral Therapy Era, Owen Ngalamika, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

With great interest, we read the recent publication “Kaposi’s sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era” by Bohlius et al. We congratulate the authors for their contribution to this field. In this study the authors observed a decrease in incidence of Kaposi’s sarcoma (KS) in patients treated with anti-retroviral therapy (ART) when compared to patients who are not on ART. These results are encouraging because of the ongoing HIV epidemic in sub-Saharan Africa where KS is still one of the most prevalent cancers. Also, it is a relevant topic to study in …

Activation And Degradation Of Open Reading Frame 45 By The Replication And Transcription Activator Of Kaposi's Sarcoma-Associated Herpesvirus, Ying Wang, Kai Yu, Xiuzhi Pei, Tiancheng Zhang, Yuying Guo, Charles Wood, Jinzhong Wang

Nebraska Center for Virology: Faculty Publications

The open reading frame 45 (ORF45) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is an immediate-early phosphorylated tegument protein critical for viral escape from host immune surveillance. Its expression is upregulated by the viral replication and transcription activator (RTA), a key protein that controls the switch from latency to lytic replication. We report here that ORF45 expression was not only upregulated by RTA, but ORF45 could also be degraded by RTA in a proteasome-dependent manner. The ORF45 was activated by RTA via activation of the ORF45 promoter, and the promoter region from nt 69 271 to nt 69 026 was involved. …

Single-Dose Cpg Immunization Protects Against A Heterosubtypic Challenge And Generates Antigen-Specific Memory T Cells, Alexander J. Vogel, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Despite extensive research, influenza A virus (IAV) remains a major cause of morbidity, mortality, and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains, such as H5N1 and pandemic H1N1, highlight the need for universal, crossprotective vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins, hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are a favorable target for developing vaccines that induce strong T cell responses in addition to humoral immunity. Here, we found that intranasal administration with a single dose of CpG and inactivated …

Long-Acting Parenteral Combination Antiretroviral Loaded Nano-Drug Delivery System To Treat Chronic Hiv-1 Infection: A Humanized Mouse Model Study, Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, Wenjin Fan, Qingsheng Li, Christopher J. Destache

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus (HIV) patients are often diagnosed in the chronic stage of HIV/AIDS. Combination antiretroviral therapy (cART) has improved quality of life for HIV-infected patients. Present study describes a novel long-acting parenteral formulation of combination antiretroviral (cARV) loaded nano-drugs for treating chronic HIV-1 (cHIV) in a humanized-BLT (hu-BLT) mice model. The cARV (elvitegravir + tenofovir alafenamide + emtricitabine; EVG + TAF + FTC) drugs (mimicking marketed Genvoy® one-pill for HIV-treatment) were encapsulated in poly (lactic-co-glycolic acid) nanoparticles (NPs). To establish cHIV, hu-BLT mice were intravaginally challenged with HIV-1 and maintained for 15 weeks. Plasma viral load (pVL) was monitored …

Mutations In The 5’ Ntr And The Non-Structural Protein 3a Of The Coxsackievirus B3 Selectively Attenuate Myocarditogenicity, Chandirasegaran Massilamany, Arunakumar Gangaplara, Rakesh H. Basavalingappa, Rajkumar A. Rajasekaran, Hiep Vu, Jean-Jack Riethoven, David Steffen, Asit K. Pattnaik, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The 5’ non-translated region (NTR) is an important molecular determinant that controls replication and virulence of coxsackievirus B (CVB)3. Previous studies have reported many nucleotide (nt) sequence differences in the Nancy strain of the virus, including changes in the 5’ NTR with varying degrees of disease severity. In our studies of CVB3-induced myocarditis, we sought to generate an infectious clone of the virus for routine in vivo experimentation. By determining the viral nt sequence, we identified three new nt substitutions in the clone that differed from the parental virus strain: C97U in the 5’ NTR; a silent mutation, A4327G, in …

Confocal Fluorescence Microscopy: An Ultra-Sensitive Tool Used To Evaluate Intracellular Antiretroviral Nano-Drug Delivery In Hela Cells, Subhra Mandal, You Zhou, Annemarie Shibata, Christopher J. Destache

School of Veterinary and Biomedical Sciences: Faculty Publications

In the last decade, confocal fluorescence microscopy has emerged as an ultra-sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular-level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the world’s major health threats by claiming approximately 7,000 new infections daily worldwide. Although combination antiretroviral drugs (cARV) therapy has improved the life-expectancy of HIV-infected patients, routine use of high doses of cARVhas serious health consequences and requires complete adherence to the regimen for success. Thus, our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co-glycolic acid) (PLGA) nanoparticles (cARV-NPs) as …

Association Of Autophagy In The Cell Death Mediated By Dihydrotestosterone In Autoreactive T Cells Independent Of Antigenic Stimulation, Ting Jia, Annandurai Anandhan, Chandirasegaran Massilamany, Rajkumar A. Rajasekaran, Rodrigo Franco, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

Gender disparity is well documented in the mouse model of experimental autoimmune encephalomyelitis (EAE) induced with proteolipid protein (PLP) 139–151, in which female, but not male, SJL mice show a chronic relapsing-remitting paralysis. Furthermore, dihydrotestosterone (DHT) has been shown to ameliorate the severity of EAE, but the underlying mechanisms of its protective effects are unclear. Using major histocompatibility complex (MHC) class II dextramers for PLP 139-151, we tested the hypothesis that DHT selectively modulates the expansion and functionalities of antigen-specific T cells. Unexpectedly, we noted that DHT induced cell death in antigen-specific, autoreactive T cells, but the effects were not …