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Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes
Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes
LSU Doctoral Dissertations
Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses …
Evaluation Of Broad Anti-Herpesviral Activity With Α-Hydroxytropolones, Shannon David Dehghanpir
Evaluation Of Broad Anti-Herpesviral Activity With Α-Hydroxytropolones, Shannon David Dehghanpir
LSU Master's Theses
Herpesviruses are ubiquitous in animals and cause economic losses concomitant with many diseases, including upper respiratory disease, keratitis, abortion, neonatal death, and neurologic disease. The majority of the domestic animal herpesviruses are within the subfamily Alphaherpesvirinae, along with the prototypical human herpes simplex virus 1 (HSV-1). Suppression of HSV-1 replication has been reported with α-hydroxytropolones (αHTs), which are aromatic ring compounds that have broad bioactivity due to potent chelating activity. It is postulated that αHTs inhibit enzymes within the nucleotidyltransferase superfamily (NTS), similarly structured enzymes that require divalent cations for nucleic acid cleavage activity. One potential herpesviral target includes the …
The Role Of Herpes Simplex Virus Type 1 Glycoprotein K In Neuroinvasion And Immunopathogenesis Of Herpes Keratitis, Ahmad Saied
The Role Of Herpes Simplex Virus Type 1 Glycoprotein K In Neuroinvasion And Immunopathogenesis Of Herpes Keratitis, Ahmad Saied
LSU Doctoral Dissertations
ABSTRACT Herpes simplex virus type 1 is a common neurotropic pathogen responsible for a multitude of human diseases ranging from mucocutaneous lesions, keratitis to life-threatening encephalitis. The hallmark of the HSV-1 life cycle is infection of sensory neurons, where the virus establishes a latent infection for the life of the host. Viral envelope glycoproteins play important roles in viral life cycle and virus-host interaction. Viral glycoproteins gK, gM, gE and the membrane protein UL11 have been shown to be important for virus assembly, egress and virus spread. To investigate the relative importance of each of gK, gM, gE and UL11 …
Comparative Roles Of Herpes Simplex Virus Type 1 (Hsv-1) Glycoproteins In Cytoplasmic Virion Egress, Hyuncheol Lee
Comparative Roles Of Herpes Simplex Virus Type 1 (Hsv-1) Glycoproteins In Cytoplasmic Virion Egress, Hyuncheol Lee
LSU Master's Theses
HSV-1 acquires its final envelope by budding into cytoplasmic vesicles thought to be derived from Trans-Golgi Network (TGN) membranes. This process is facilitated by interactions among the carboxyl termini of viral glycoproteins and tegument proteins. To investigate the relative importance of different viral glycoproteins in cytoplasmic virion morphogenesis, a set of recombinant viruses were constructed silencing expression of the glycoprotein E (ΔgE), the carboxyl terminus of glycoprotein D (gDΔcp), and the membrane protein UL20 (ΔUL20). In addition, recombinant viruses were constructed having the ΔgE+gDΔcp, and the ΔgE+ΔgM (glycoprotein M) deletions. These recombinant viruses were constructed using the double-red, site-directed mutagenesis …
Novel Oncolytic Herpesviruses For Breast Cancer Treatment, Anna Israyelyan
Novel Oncolytic Herpesviruses For Breast Cancer Treatment, Anna Israyelyan
LSU Doctoral Dissertations
Oncolytic herpes simplex virus type-1 (HSV-1) has shown great potential as an effective agent for cancer therapy ¨C oncolytic virotherapy. To enhance oncolytic capabilities of previously reported agents, new oncolytic and fusogenic HSV-1 OncSyn and OncdSyn viruses were constructed based on wild type HSV-1 (F) strain. To provide for safety and tumor selectivity, the viruses carried a large deletion including one of the two ¦Ã134.5 genes. The ¦Ã134.5 gene, a major neurovirulence factor, was replaced by a gene cassette constitutively expressing the red fluorescent protein. Homologous recombination was utilized to transfer the fusogenic gBsyn3 mutation to the viral genome to …