A5102924530- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Poxvirus research and outbreaks
- interferon and immune responses
- Animal Virus Infections Studies
- Immune Response and Inflammation
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Bacteriophages and microbial interactions
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Research and Treatments
- Inflammasome and immune disorders
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- RNA Interference and Gene Delivery
- Polyomavirus and related diseases
- Ocular Diseases and Behçet’s Syndrome
- Toxoplasma gondii Research Studies
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Plant Virus Research Studies
- Bacillus and Francisella bacterial research
- NF-κB Signaling Pathways
- Viral gastroenteritis research and epidemiology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Arizona State University
2018-2019
University of Florida
2008-2017
Moffitt Cancer Center
2016
University of Calgary
2010-2016
National Cancer Institute
2016
Center for Cancer Research
2016
Florida College
2013-2015
University of Massachusetts Chan Medical School
2011
Memorial Sloan Kettering Cancer Center
2011
Cornell University
2011
Abstract Oncolytic myxoma virus (MYXV) is being developed as a novel virotherapeutic against human brain cancer and has promising activity tumor models in immunocompromised hosts. Because an intact immune system could reduce its efficacy, the purpose of this study was to evaluate oncolytic potential MYXV immunocompetent racine glioma models. Here, we report that infects kills all cell lines effects are enhanced by rapamycin. Intratumoral administration with rapamycin improved viral...
The sensing of pathogen infection and subsequent triggering innate immunity are key to controlling zoonotic infections. Myxoma virus (MV) is a cytoplasmic DNA poxvirus that in nature infects only rabbits. Our previous studies have shown MV primary mouse cells restricted by virus-induced type I interferon (IFN). However, little known about the sensor(s) involved activating signaling pathways leading cellular defense responses human immune cells. Here, we show complete restriction fibroblasts...
Abstract Myxoma virus (MYXV) is a member of the Poxviridae family and prototype for genus Leporipoxvirus . It pathogenic only European rabbits, in which it causes lethal disease myxomatosis, two North American species, less severe disease. MYXV replicates exclusively cytoplasm host cell. Although not infectious humans, its genome encodes proteins that can interfere with or modulate defense mechanisms; able to productively infect number human cancer cell lines, but normal cells, has also been...
Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family dsRNA-binding proteins that antagonize cellular interferon signaling pathways. In order to investigate additional functions M029, we have constructed series targeted M029-minus (vMyx-M029KO and vMyx-M029ID) V5-tagged MYXV. We found plays pivotal role in determining tropism MYXV all mammalian cells tested. The viruses were able replicate only engineered cell lines stably express complementing protein, such as...
Significance The virulence and host range of viruses is controlled by the interaction innate immune system with viral molecules. This an important driver for evolution both virus. attenuation myxoma virus, a rabbit-specific poxvirus, after its deliberate release to control European rabbit populations, increased resistance rabbits, one best-known examples host–virus coevolution on population level. We show that virus protein M156 specifically inhibited antiviral kinase R (PKR) from rabbits...
Myxoma virus (MYXV) is a promising oncolytic agent and highly effective against immortalized glioma cells but less brain tumor initiating (BTICs), which are believed to mediate development/recurrence. MYXV encodes various proteins attenuate host cell apoptosis, including an antiapoptotic Bcl-2 homologue known as M011L. Such may limit the ability of kill BTICs, have heightened resistance apoptosis. We hypothesized that infecting BTICs with M011L-deficient construct would overcome BTIC MYXV.We...
Effector-triggered immunity (ETI) is a form of pathogen sensing that involves detection pathogen-encoded virulence factors or 'effectors'. To discover novel ETI pathways in mammals, we developed screening approach which individual are expressed human monocytes and transcriptional responses assessed by RNA-seq. Using this approach, identify poxvirus effector, myxoma virus M3.1, elicits an anti-viral NF-κB response. We find unleashed pathway senses M3.1 attack two complexes: ZAP TBK1....
Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating tropism pathogenesis. Here, we present first systematic protein interaction screening unique variola virus proteome by using yeast 2-hybrid against variety human cDNA libraries. Several protein–protein were identified, including an G1R, ankryin/F-box containing protein, nuclear factor kappa-B1 (NF-κB1)/p105. This represents direct pathogen-encoded NF-κB1/p105. Orthologs G1R...
NF-kappaB and inflammasomes both play central roles in orchestrating anti-pathogen responses by rapidly inducing a variety of early-response cytokines chemokines following infection. Myxoma virus (MYXV), pathogenic poxvirus rabbits, encodes member the cellular pyrin domain (PYD) superfamily, called M013. The viral M013 protein was previously shown to bind host ASC-1 inhibit inflammasome complex that regulates activation secretion caspase 1-regulated such as IL-1beta IL-18. Here, we report...
Vaccinia virus, a large double-stranded DNA is the prototype of Orthopoxvirus genus, which includes several pathogenic poxviruses humans, such as monkeypox virus and variola virus. Here, we report comprehensive yeast two-hybrid (Y2H) screening for protein-protein interactions between vaccinia human proteins. A total 109 novel vaccinia-human protein were detected among 33 viral To validate subsets those interactions, constructed an ORFeome library strain WR using Gateway plasmid cloning...
Myxoma virus (MYXV) is a well-established oncolytic agent against different types of tumors. MYXV also known for its immunomodulatory properties in down-regulating major histocompatibility complex (MHC) I surface expression (via the M153R gene product, viral E3-ubiquitin ligase) and suppressing T cell killing infected target cells. MHC down-regulation, however, favors NK activation. Brain tumors including gliomas are characterized by high with impaired activity. We thus hypothesized that...
Many pathogenic orthopoxviruses like variola virus, monkeypox and cowpox virus (CPXV), but not vaccinia encode a unique family of ankyrin (ANK) repeat-containing proteins that interact directly with NF-kappaB1/p105 inhibit the NF-kappaB signaling pathway. Here, we present in vitro vivo characterization targeted gene knockout this novel inhibitor CPXV. Our results demonstrate vCpx-006KO uniquely induces variety NF-kappaB-controlled proinflammatory cytokines from infected myeloid cells,...
ABSTRACT The myxoma virus (MYXV)-encoded pyrin domain-containing protein M013 coregulates inflammatory responses mediated by both the inflammasome and NF-κB pathways. Infection of human THP-1 monocytic cells with a MYXV construct deleted for gene (vMyxM013-KO), but not parental MYXV, activates pathways induces spectrum proinflammatory cytokines chemokines, like interleukin-1β (IL-1β), tumor necrosis factor (TNF), IL-6, monocyte chemoattractant 1. Here, we report that vMyxM013-KO...
ABSTRACT Poxviruses are large DNA viruses that replicate in the cytoplasm of infected cells. Myxoma virus is a rabbit poxvirus belongs to Leporipoxvirus genus. It causes lethal disease called myxomatosis European rabbits but cannot sustain any detectable infection nonlagomorphs. Vaccinia prototypal orthopoxvirus was used as vaccine eradicate smallpox. nonpathogenic mice, whereas systemic with vaccinia can be even immunocompetent mice. Plasmacytoid dendritic cells (pDCs) potent type I...
Hematological malignancies such as leukemias, lymphomas, multiple myeloma (MM), and the myelodysplastic syndromes (MDSs) primarily affect adults are difficult to treat. For high-risk disease, hematopoietic stem cell transplant (HCT) can be used. However, in setting of autologous HCT, relapse due contamination autograft with cancer cells remains a major challenge. Ex vivo manipulations purge using chemotherapies toxins have been attempted. Because these past strategies lack specificity for...
Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM) can arm become more effective killers in vitro an immunodeficient xenotransplant murine model. Here, we tested ex vivo MYXV virotherapy MM immunocompetent mice using allogeneic mouse-mouse In contrast all lines previously tested, line...
Inflammation of the retina is a contributing factor in ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration (AMD). The M013 immunomodulatory protein from myxoma virus has been shown to interfere with proinflammatory signaling pathways involving both NLRP3 inflammasome NF-κB. We have developed characterized an adeno-associated viral (AAV) vector that delivers secretable cell-penetrating form (TatM013). expressed TatM013 was secreted blocked...