FeLV Infection: A Model of Effective Retroviral Immunity

候选人Andrea N.Torres，DVM的直接目标是完成一个有指导的项目 研究逆转录病毒免疫调节和发病机制，最终获得博士学位和其他博士后研究经验。托雷斯博士的长期目标是成为一名首席研究员，从事针对动物和人类病毒疾病的免疫调节策略研究。研究培训计划将集中在赞助商科罗拉多州立大学爱德华·A·胡佛博士的实验室。该环境在外部资金和医学科学家培训方面有着良好的记录。候选人的培训计划包括应用于逆转录病毒免疫缺陷动物模型的当代细胞和分子病毒学研究方法的实验室和教学指导。这项拟议的研究考察了早期的细胞和体液免疫反应，这些反应区分了利用猫白血病病毒(FeLV)感染来有效遏制逆转录病毒感染和无效遏制逆转录病毒感染的有效性。 自然产生的直径宿主模型：逆转录病毒关系。我们将解决两个特定的目标：(1)第一，确定早期细胞因子平衡与体内FeLV感染消退和进展的关系；(2)第二，确定早期操纵1型和II型细胞因子平衡是否可以诱导FeLV感染的消退或进展。在目标1中，我们将检测FeLV-NATve和FeLV疫苗接种的猫的早期病毒感染和免疫反应动力学。我们将对血液和淋巴组织细胞进行病毒DNA、RNA、蛋白质和传染性的系列分析 通过实时定量DNA和RNA聚合酶链式反应、p27Gag捕获和病毒分离。我们将通过定量实时rna pcr检测循环和淋巴组织1型和2型细胞因子转录本、病毒中和抗体、FeLV特异性T细胞溶解和辅助细胞活性来评估可能的早期免疫保护相关性。在目标2中，我们将确定对1型或2型应答的初始免疫反应的操纵是否与通过给予外源性猫白介素12或白介素10进行更有效的逆转录病毒遏制相关，外源性猫白介素12或白介素10经腺病毒载体在黏膜中或附近输送。 粘膜FeLV攻击时间。然后将使用AIM 1中应用的方法分析IL-12、IL-10和假载体处理的动物中宿主与病毒的关系。这些研究的结果应该有助于深入了解逆转录病毒感染的早期有效宿主控制和无效宿主控制。

The immediate goal of the candidate, Andrea N. Torres, DVM, is to complete a mentored program investigating retrovirus immunoregulation and pathogenesis, culminating in the PhD degree and additional postdoctoral research experience. Dr. Torres' long-term goal is to become a principal investigator conducting research on immunomodulatory strategies against viral diseases of animals and humans. The research training program will be centered in the laboratory of sponsor Dr. Edward A. Hoover at Colorado State University. The environment has a strong record of extramural funding and medical scientist training. The candidate's training plan involves laboratory and didactic instruction in contemporary cellular and molecular virology research methods applied to an animal model of retroviral immunodeficiency. The proposed research examines the early cellular and humoral immune responses which distinguish effective vs. ineffective containment of retroviral infection by using the feline leukemia virus (FeLV) infection, a naturally occurring model of diametric host:retrovirus relationships. We will address two specific aims: (1) first, to determine the relationship of early cytokine balance to regression vs. progression of FeLV infection in vivo; and (2) second, to determine whether early manipulation of the type 1 and type 2 cytokine balance can induce regression or progression of FeLV infection. In Aim 1, we will examine early viral infection and immune response kinetics in FeLV-naTve and FeLV-vaccinated cats challenged oral-nasally with FeLV-61E. We will perform serial analysis of blood and lymphoid tissue cells for viral DNA, RNA, protein, and infectivity by quantitative real-time DNA and RNA PCR, p27 Gag capture, and virus isolation. We will assess possible early immune correlates of protection by quantitative real-time RNA PCR for circulating and lymphoid tissue type 1 and type 2 cytokine transcripts, virus neutralizing antibody, FeLV-specific T cytolytic and helper cell activity, in Aim 2, we will determine whether manipulation of the initial immune response toward a type 1 or type 2 response will correlate with more vs. less effective retroviral containment via administration of exogenous feline interleukin-12 or interleukin-10, delivered mucosally via adenovirus vectors at or near the time of mucosal FeLV challenge. The host:virus relationship in IL-12-, IL-10-, and sham vector-treated animals will then be analyzed using methodologies applied in Aim 1. The results of these studies should provide insight into the early effective vs. ineffective host control of retrovirus infections.