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Department of Microbiology and Immunology Faculty Papers

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Full-Text Articles in Medicine and Health Sciences

Investigating The Role For Il-21 In Rabies Virus Vaccine-Induced Immunity., Corin L Dorfmeier, Evgeni P Tzvetkov, Anthony Gatt, James P Mcgettigan Jan 2013

Investigating The Role For Il-21 In Rabies Virus Vaccine-Induced Immunity., Corin L Dorfmeier, Evgeni P Tzvetkov, Anthony Gatt, James P Mcgettigan

Department of Microbiology and Immunology Faculty Papers

Over two-thirds of the world's population lives in regions where rabies is endemic, resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (PEP) and over 55,000 deaths per year globally. A major goal in rabies virus (RABV) research is to develop a single-dose PEP that would simplify vaccination protocols, reduce costs associated with RABV prevention, and save lives. Protection against RABV infections requires virus neutralizing antibodies; however, factors influencing the development of protective RABV-specific B cell responses remain to be elucidated. Here we used a mouse model of IL-21 receptor-deficiency (IL-21R-/-) to characterize the role for IL-21 in RABV …


Buffered Memory: A Hypothesis For The Maintenance Of Functional, Virus-Specific Cd8(+) T Cells During Cytomegalovirus Infection., Christopher M Snyder Dec 2011

Buffered Memory: A Hypothesis For The Maintenance Of Functional, Virus-Specific Cd8(+) T Cells During Cytomegalovirus Infection., Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and …


Sustained Cd8+ T Cell Memory Inflation After Infection With A Single-Cycle Cytomegalovirus., Christopher M Snyder, Kathy S Cho, Elizabeth L Bonnett, Jane E Allan, Ann B Hill Oct 2011

Sustained Cd8+ T Cell Memory Inflation After Infection With A Single-Cycle Cytomegalovirus., Christopher M Snyder, Kathy S Cho, Elizabeth L Bonnett, Jane E Allan, Ann B Hill

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) is a β-herpesvirus that establishes a lifelong latent or persistent infection. A hallmark of chronic CMV infection is the lifelong persistence of large numbers of virus-specific CD8+ effector/effector memory T cells, a phenomenon called "memory inflation". How the virus continuously stimulates these T cells without being eradicated remains an enigma. The prevailing view is that CMV establishes a low grade "smoldering" infection characterized by tiny bursts of productive infection which are rapidly extinguished, leaving no detectable virus but replenishing the latent pool and leaving the immune system in a highly charged state. However, since abortive reactivation with limited …


Hydrophobicity As A Driver Of Mhc Class I Antigen Processing., Lan Huang, Matthew C Kuhls, Laurence C. Eisenlohr Apr 2011

Hydrophobicity As A Driver Of Mhc Class I Antigen Processing., Lan Huang, Matthew C Kuhls, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

The forces that drive conversion of nascent protein to major histocompatibility complex (MHC) class I-restricted peptides remain unknown. We explored the fundamental property of overt hydrophobicity as such a driver. Relocation of a membrane glycoprotein to the cytosol via signal sequence ablation resulted in rapid processing of nascent protein not because of the misfolded luminal domain but because of the unembedded transmembrane (TM) domain, which serves as a dose-dependent degradation motif. Dislocation of the TM domain during the natural process of endoplasmic reticulum-associated degradation (ERAD) similarly accelerated peptide production, but in the context of markedly prolonged processing that included nonnascent …


Inhibition Of Oncogene-Induced Inflammatory Chemokines Using A Farnesyltransferase Inhibitor., Katharine C Degeorge, Brent R Degeorge, James S Testa, Jay L Rothstein Jan 2008

Inhibition Of Oncogene-Induced Inflammatory Chemokines Using A Farnesyltransferase Inhibitor., Katharine C Degeorge, Brent R Degeorge, James S Testa, Jay L Rothstein

Department of Microbiology and Immunology Faculty Papers

ABSTRACT: BACKGROUND: Farnesyltransferase inhibitors (FTI) are small molecule agents originally formulated to inhibit the oncogenic functions of Ras. Although subsequent analysis of FTI activity revealed wider effects on other pathways, the drug has been demonstrated to reduce Ras signaling by direct measurements. The purpose of the current study was to determine if FTI could be used to inhibit the inflammatory activities of a known Ras-activating human oncoprotein, RET/PTC3. RET/PTC3 is a fusion oncoprotein expressed in the thyroid epithelium of patients afflicted with thyroid autoimmune disease and/or differentiated thyroid carcinoma. Previous studies have demonstrated that RET/PTC3 signals through Ras and can …