A5103038967- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Viral-associated cancers and disorders
- HIV Research and Treatment
- CNS Lymphoma Diagnosis and Treatment
- Herpesvirus Infections and Treatments
- Virus-based gene therapy research
- Virology and Viral Diseases
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- Lymphoma Diagnosis and Treatment
- Pneumonia and Respiratory Infections
- Mosquito-borne diseases and control
- Cardiac tumors and thrombi
- Toxoplasma gondii Research Studies
- Cellular transport and secretion
- Hepatitis B Virus Studies
- Ubiquitin and proteasome pathways
- Hepatitis C virus research
- interferon and immune responses
- Nosocomial Infections in ICU
- CAR-T cell therapy research
- Pediatric health and respiratory diseases
Oregon Health & Science University
2004-2024
Oregon National Primate Research Center
2024
Children's Cancer Therapy Development Institute
2009
Vollum Institute
2006
Yale University
2006
Vaccine and Gene Therapy Institute
2002-2006
ABSTRACT Poxviruses and gamma-2 herpesviruses share the K3 family of viral immune evasion proteins that inhibit surface expression glycoproteins such as major histocompatibility complex class I (MHC-I), B7.2, ICAM-1, CD95(Fas). contain an amino-terminal PHD/LAP or RING-CH domain followed by two transmembrane domains. To examine whether human homologues are functionally related to immunoevasins, we studied seven membrane-associated (MARCH) proteins. All MARCH located subcellular membranes,...
K3/MIR1 and K5/MIR2 of Kaposi's sarcoma-associated herpesvirus (KSHV) are viral members the membrane-associated RING-CH (MARCH) ubiquitin ligase family contribute to immune evasion by directing conjugation immunostimulatory transmembrane proteins. In a quantitative proteomic screen for novel host cell proteins downregulated immunomodulators, we previously observed that K5, as well human immunodeficiency virus type 1 (HIV-1) immunomodulator VPU, reduced steady-state levels bone marrow stromal...
ABSTRACT The genomes of several poxviruses contain open reading frames with homology to the K3 and K5 genes Kaposi's sarcoma-associated herpesvirus (KSHV) gene murine gammaherpesvirus 68, which target major histocompatibility complex class I (MHC-I) as well costimulatory molecules for proteasomal or lysosomal degradation. homologous product myxomavirus (MV), M153R, was recently shown reduce cell surface expression MHC-I. In addition, normal MHC-I observed in cells infected MV lacking M153R...
Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) well-characterized epitopes at different positions within viral genes and observed...
The nonpolymorphic major histocompatibility complex E (MHC-E) molecule is up-regulated on many cancer cells, thus contributing to immune evasion by engaging inhibitory NKG2A/CD94 receptors NK cells and tumor-infiltrating T cells. To investigate whether MHC-E expression can be targeted for MHC-E–restricted cell control, we immunized rhesus macaques (RM) with cytomegalovirus (RhCMV) vectors genetically programmed elicit CD8 + express established tumor-associated antigens (TAAs) including...
Membrane-associated RING-CH (MARCH) proteins represent a family of transmembrane ubiquitin ligases modulating intracellular trafficking and turnover protein targets. While homologous encoded by gamma-2 herpesviruses leporipoxviruses have been studied extensively, limited information is available regarding the physiological targets cellular MARCH proteins. To identify host cell targeted human MARCH-VIII ligase we used stable isotope labeling amino-acids in culture (SILAC) to monitor...
Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that is a broadly acting antiviral host protein. Unexpectedly however, recovery human cytomegalovirus (HCMV) from supernatants BST2-expressing fibroblasts was increased rather than decreased. Furthermore, seemed enhance entry...
Vascular endothelial cadherin (VE-cadherin) connects neighboring cells (ECs) via interendothelial junctions and regulates EC proliferation adhesion during vasculogenesis angiogenesis. The cytoplasmic domain of VE-cadherin recruits alpha- beta-catenins gamma-catenin, which interact with the actin cytoskeleton, thus modulating cell morphology. Dysregulation adherens junction/cytoskeletal axis is a hallmark invasive tumors. We now demonstrate that transmembrane ubiquitin ligase K5/MIR-2...
Abstract Currently 247 million people are living with chronic hepatitis B virus infection (CHB), and the development of novel curative treatments is urgently needed. Immunotherapy an attractive approach to treat CHB, yet therapeutic approaches augment endogenous (HBV)–specific T cell response in CHB patients have demonstrated little success. In this study, we show that strain 68-1 rhesus macaque (RM) CMV vaccine vectors expressing HBV Ags engender HBV-specific CD8+ cells unconventionally...
Rhesus cytomegalovirus (RhCMV) vectors elicit major histocompatibility complex (MHC)–E–restricted CD8 + T cells that stringently control simian immunodeficiency virus (SIV) in rhesus macaques. These responses require deletion of eight RhCMV chemokine-like open reading frames (ORFs) are conserved human (HCMV). To determine whether HCMV encodes additional, nonconserved inhibitors unconventional cell priming, we inserted 41 HCMV-specific ORFs into a chemokine-deficient strain (68-1 RhCMV)....
Abstract Genetically modified strain 68-1 rhesus cytomegalovirus (RhCMV)-derived vaccine vectors uniquely elicit CD8+ T cells recognizing peptides presented by non-polymorphic MHC-E instead of conventional MHC-I molecules. Since (HLA-E in humans) is a ligand for inhibitory receptors on NK cells, the upregulation known immune evasion strategy both cancers and intracellular pathogens. Indeed, using tissue arrays we observed that early stage prostate cancer tissues express high levels HLA-E, as...
Abstract Rhesus cytomegalovirus (RhCMV) strain 68-1 vectored vaccines elicit MHC-II-and MHC-E-, but not classical, MHC-Ia-restricted CD8+ T cell responses. This is due to the presence of a viral MHC-E ligand encoded by Rh67 (UL40 in HCMV) and combined deletion or inactivation Rh157.5/.4 (UL128/UL130 Rh158–Rh161 (members UL146 family CXC chemokines). Importantly, ability MHC-E-restricted responses correlates with efficacy RhCMV-vectored control clear infection highly virulent simian...
Abstract Pre-clinical models in non-human primates demonstrate that cytomegalovirus (CMV)-vectored vaccines are unique their ability to elicit and indefinitely maintain high frequencies of polyfunctional effector memory T cells heterologous pathogen antigens, including animals already chronically CMV infected. By introducing defined genetic modifications into the backbone it is possible program CD8+ cell responses either directed MHC-I, MHC-II or non-classical MHC-I molecule MHC-E. In...