EARLY CYTOKINE & CHEMOKINE GENE EXPRESSION IN SIV INFECTION

早期细胞因子

• 批准号: 6277750
• 负责人: ANDREW A LACKNER
• 金额: $ 8.77万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277750
• 关键词: AIDS; Mammalia; Primates; immunology; infection; inflammation; lymphatic system; virus

Competitive PCR was used to evaluate the expression of cytokine, granzyme B, and chemokine genes in lymph nodes of macaques recently infected with the simian immunodeficiency virus (SIV) pathogenic molecular clone SIVmac239 (n = 16), the nonpathogenic vaccine strain SIVmac239 D nef (n = 8), and the nonpathogenic molecular clone SIVmacA11 (n = 8). For both SIVmac239 and its nef-deleted derivative, strong expression was observed as early as 7 days postinfection for interleukin 1b(IL-1b, IL-6, tumor necrosis factor alpha, gamma interferon and IL-13. The levels of gene induction were equally intense for both viruses despite a lower viral load for SIVmac239 Dnef compared with that for SIVmac239. However, the nature of the cytokine network activation varied with the viral inocula. Primary infection with SIVmac129 was characterized by a higher level of IL-4, IL-10, MIL-1a, MIP-1b, MCP-1, and RANTES gene expression and a lower level of IL-12 and granzyme B gene expression compared with infection with SIVmac239Dnef. Thus, infection with nef-deleted SIV was associated with a preferential TH1 versus TH2 pattern of cytokine production. Infection with SIVmacA11 was characterized by a delayed immune response for all markers tested. The unique patterns of cytokine and chemokine gene expression in lymph nodes correlated nicely with the pathogenic potential of the SIV strains used as well as with differences in their ability to serve as protective vaccines.

采用竞争性PCR检测细胞因子的表达， 淋巴结中粒酶B和趋化因子基因的研究进展 感染猴免疫缺陷病毒（SIV）的致病性 分子克隆SIVmac 239（n = 16），非致病性疫苗株 SIVmac 239 D nef（n = 8）和非致病性分子克隆 SIVmacA11（n = 8）。 对于SIVmac 239及其nef缺失衍生物， 早在感染后7天就观察到强表达， 白细胞介素1b（IL-1b，IL-6，肿瘤坏死因子α，γ 干扰素和IL-13。 基因诱导水平相同 尽管SIVmac 239 Dnef的病毒载量较低，但两种病毒均为强 与SIVmac 239相比。 然而，细胞因子的性质 网络激活随病毒接种物而变化。 原发感染 SIVmac 129的特征是IL-4，IL-10， MIL-1a、MIP-1b、MCP-1和RANTES基因表达以及较低水平的 IL-12和颗粒酶B基因表达与感染 SIVmac239Dnef. 因此，nef缺失的SIV感染与 细胞因子产生的优先模式为TH 1对TH 2。 SIVmacA 11感染的特点是延迟免疫 所有检测标志物的响应。 细胞因子的独特模式和 淋巴结中的趋化因子基因表达与 所用SIV毒株的致病潜力以及 它们作为保护性疫苗的能力存在差异。