Thesis (M. S.)--Texas A&M University, 2007. / "Major Subject: Veterinary Medical Sciences" Title from author supplied metadata (automated record created on Oct. 13, 2008.) Vita. Abstract. Includes bibliographical references.

Thesis (M. S.)--Texas A&M University, 2003 / "Major Subject: Veterinary Medical Sciences" Title from author supplied metadata (automated record created on Feb. 17, 2005.) Vita. Abstract. Includes bibliographical references.

"Major Subject: Veterinary Medical Sciences" Title from author supplied metadata (automated record created 2010-03-12 12:08:51). Includes bibliographical references.

"Major Subject: Veterinary Medical Sciences" Title from author supplied metadata (automated record created 2010-03-12 12:08:51). Includes bibliographical references.

"Major Subject: Veterinary Medical Sciences" Title from author supplied metadata (automated record created 2010-03-12 12:08:51). Includes bibliographical references.

"Major Subject: Veterinary Medical Sciences" Title from author supplied metadata (automated record created 2010-03-12 12:08:51). Includes bibliographical references.

Obesity can have numerous detrimental consequences, namely metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer, and Alzheimers disease. The pathogenesis and physiologic consequences of obesity are unknown, but they are often associated with increased inflammation and oxidative stress in both the body and in the brain. One factor that has been implicated in causing inflammation associated with a high fat diet is the enzyme NADPH oxidase, or NOX, specifically the subunit NOX2. Two studies were performed in order to assess the effects of a high fat diet in combination with a universal NOX2 deficiency and a NOX2 deficiency targeted to macrophages. The results of the first study indicate that the NOX2 knockout (NOX2KO) mice on a high fat diet do not experience all the deleterious metabolic and inflammatory effects in the body and brain to the same degree as wild-type mice. This suggests that a deficiency in NOX2 does offer protection from some of the deleterious effects of a high fat diet. It was also determined from the first study that NOX2 expression is localized to macrophages in the visceral adipose tissue. In order to target these macrophages, a second study was conducted. For this second study, a mouse model was genetically engineered with the intent of inhibiting NOX2 solely within macrophages. Similar to the first study, these macrophage-deficient NOX2 knockout (macNOX2KO) mice were placed on a high fat along with the NOX2-flox wild-type (WT-FL) mice. The results suggest that the macrophage-deficient NOX2 knockout mice were protected from the deleterious effects of a high fat diet. In summary, the deletion of NOX2 appears to offer a protective benefit against the deleterious effects of obesity in the context of a high fat diet. Specifically, the deletion of NOX2 in macrophages also offers this protection with the added benefit of targeting the deletion so as to not affect NOX2 functioning in other cells in the body.

Spotted fever group (SFG) Rickettsia are primarily associated with their reservoir host and vector, the tick. Rickettsial colonization and maintenance within the arthropod is a key component of vector competence and pathogen transmission to the mammalian host. Contemporary detection of novel tick hosts for rickettsial species, combined with an unprecedented rise in human cases of SFG rickettsiosis, necessitates a deeper understanding of tick/Rickettsia interactions. The hypothesis for this work is that if primary tick/Rickettsia pairings do not exist then rickettsial determinants account for primary vector/pathogen relationships. To this end, Dermacentor variabilis and Amblyomma maculatum ticks were exposed to R. rickettsii, R. parkeri, R. montanensis, R. amblyommii or R. felis. Rickettsial exposure negatively impacted the fitness of A. maculatum, but not D. variabilis. Transovarial and transtadial transmission of rickettsiae was most successful for R. amblyommii and R. parkeri in both, A. maculatum and D. variabilis eggs, larvae, and nymphs. Maintenance of rickettsiae in both tick species via transstadial transmission was diminished from unfed larvae to unfed F1 adults. To further investigate the maintenance of Rickettsia in the arthropod host, an in vitro and in vivo model of R. parkeri infection was utilized. Rickettsial proteins implicated in intracellular actin-based motility (Sca2 and RickA) were shown to function similarly in mammalian and tick cell culture, suggesting conserved functionality in both hosts. In vivo dissemination of a wild-type strain of R. parkeri was measured against two strains deficient in Sca2 and RickA expression. Wild-type, RickA, and Sca2 deficient strains R. parkeri persisted in all tick organs organs at 7 days post-exposure. The findings suggest transovarial transmission specificity to be tick species dependent and vertical transmission is not sustainable.

Ticks are important worldwide as vectors of bacteria, viruses, and parasites. Pathogenic and non-pathogenic Spotted fever group (SFG) Rickettsia are maintained and transmitted by ticks with specific hard tick-Rickettsia pairings evident in nature. The pathogenic SFG Rickettsia rickettsii is transmitted by the hard tick Dermacentor variabilis. In response to infection, D. variabilis is known differentially respond to SFG Rickettsia infection. The mechanisms of differential immune induction are currently unknown, and are likely involved in the establishment of specific tick-SFG Rickettsia pairings. It was hypothesized that the level of response by D. variabilis to SFG Rickettsia occurs in a species-specific manner, and that this response drives vector competence. To this end, we report the isolation of an mRNA transcript, dvrelish, using RACE-PCR. Conserved domain analysis of dvrelish identified a Rel-homolgy domain, allowing for its identification as encoding a putative Relish-type NF-κB protein. DvRelish was identified via Western blot, immunofluorescence assay and MALDI-TOF/TOF mass-spectrometry. Tick infection assays were performed using microinjection and capillary feeding technique methodologies to identify dvrelish expression in response to SFG Rickettsia infection. Microinjection of 107 R. rickettsii induced the increased expression of dvrelish in hemocytes at 1 hour post injection, and in combined tissues at 6 hours post injected. Injection with similar and lower doses of P. aeruginosa and Rickettsia parkeri did not significantly change dvrelish expression. When capillary fed R. rickettsii, dvrelish expression increased in hemocytes after 1 hour exposure and decreased after a 3 hour exposure. Together, the expression of dvrelish was dose and tissues specific in response to SFG Rickettsia challenge. Understanding the molecular regulation of immunological response to rickettsial infection in ticks may better define the mechanisms of vector competence and the epidemiology of SFG rickettsioses.

Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV infection indicating that a similar vaccine approach may be feasible for HSVs. In this dissertation, we summarize pre-clinical approaches to HSV vaccine development and current efforts to test certain vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1 vaccine strain to protect against both HSV-1 and HSV-2 infections.