ALVEOLAR MACROPHAGES IN FIV INFECTION

描述：(改编自应用程序)对更好的 了解HIV相关肺部疾病的发病机制是一种 与HIV相关免疫缺陷类似的动物慢病毒模型。 有证据表明，导致猫科艾滋病的慢病毒，猫咪 免疫缺陷病毒(FIV)导致严重的肺部免疫缺陷 特点是对弓形虫肺炎的易感性增加。 拟议的研究将使用FIV来检查缺陷 在肺泡巨噬细胞(AM)功能中。该应用程序描述了实验 旨在检验两个假设：首先， HIV/FIV患者AM的激活是病毒感染的直接结果 独立于淋巴因子调节的AM；第二，HIV/FIV 感染抑制自分泌干扰素-伽马环路 用于生产IL-12的Prime AM。 A.职业发展计划：该计划分为两个阶段。在.期间 在第一阶段，里奇博士将完成他的博士培训。他走进了 1993年7月攻读博士学位，现已完成授课培训 以及初步检查。在第二阶段(第三和第四年)， 里奇博士将继续留在北卡罗来纳州立大学，在 博士后职位。 B.研究计划：猫免疫缺陷病毒(FIV)将用于 检查肺泡巨噬细胞(AM)功能缺陷。实验是 计划检验两个假设：第一，本构水平 HIV/FIV患者AM的激活是病毒感染的直接结果 独立于淋巴因子调节的AM；第二，HIV/FIV 感染抑制AM启动所必需的自分泌干扰素-伽马环路 IL-12生产。该计划头三年的学习将 通过评估AM的细胞因子表达模式来检验这些假说 在体内感染FIV后以临时方式收集。最后 这项研究的年份将与体外研究的结果相关联 用弓形虫对感染FIV的猫进行体内攻击。

DESCRIPTION: (Adapted from the application) Critical to a better understanding of the pathogenesis of HIV-associated lung disease is an animal lentivirus model that parallels HIV-associated immunodeficiency. Evidence suggests that the feline AIDS-causing lentivirus, Feline Immunodeficiency Virus (FIV) causes serious pulmonary immunodeficiency characterized by increased susceptibility to Toxoplasma gondii pneumonia. The proposed research will employ the use of FIV for examining the defects in alveolar macrophage (AM) function. The application describes experiments designed to test two hypotheses: first, that the constitutive level of activation of AM from HIV/FIV patients is a direct result of viral infection of the AM independent of lymphokine conditioning; secondly, that HIV/FIV infection inhibits an autocrine interferon (IFN)-gamma loop necessary to prime AM for IL-12 production. a. Career Development Plan: The plan consists of two phases. During the first Phase, Dr. Ritchey will complete his Ph.D. training. He entered the Ph.D. program in July of 1993, and has completed the didactic training as well as the preliminary examination. In phase two (years three and four), Dr. Ritchey will remain at North Carolina State University, in a postdoctoral position. b. Research Plan: Feline Immunodeficiency Virus (FIV) will be used to examine the defects in alveolar macrophage (AM) function. Experiments are planned to test two hypotheses: first, that the constitutive level of activation of AM from HIV/FIV patients is a direct result of viral infection of the AM independent of lymphokine conditioning; secondly, that HIV/FIV infection inhibits an autocrine IFN-gamma loop necessary to prime AM for IL-12 production. Studies during the first three years of this program will test these hypotheses by evaluating cytokine expression patterns of AM collected in a temporal fashion following in vivo FIV infection. The last year of this research will correlate the results of the in vitro studies with in vivo challenge of FIV-infected cats with T. gondii.