ROLE OF TLR 4 IN MMTV INFECTION OF B LYMPHOCYTES

TLR 4 在 B 淋巴细胞 MMTV 感染中的作用

• 批准号: 6514910
• 负责人: JOHN C RASSA
• 金额: $ 4.42万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-16 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6514910
• 关键词: B lymphocyte; Retroviridae disease; gel mobility shift assay; genetic transcription; laboratory mouse; leukocyte activation /transformation; lipopolysaccharides; mouse mammary tumor virus; nuclear factor kappa beta; virus antigen; virus envelope; virus genetics; virus infection mechanism; virus receptors

Mouse mammary tumor virus (MMTV) is a type B retrovirus which causes mammary gland carcinomas in susceptible mice. The virus is transmitted to new born pups by nursing on infected mother's milk and results in the initial infection of B cells in the Peyer's patches. Similar to most retroviruses, MMTV infection and replication requires the target cell to be in an activated state. Currently, the mechanism of activating the initial B cell target population is not understood. The Tlr-4 protein is an integral component of the LPS signal transduction pathway which results in high levels of lymphocyte activation. We have preliminary evidence that the MMTV Env protein binds to the Tlr-4 protein. C3H/HeJ mice which are deficient in LPS induced signaling exhibit reduced MMTV virulence and reduced endogenous MMTV gene expression in the presence of LPS. The goal of this work is to understand the molecular interaction between mouse mammary tumor virus (MMTV) Env and Tlr-4 and to determine the role of Tlr-4 mediated cellular activation on the early stages of MMTV pathogenesis in B cells.

小鼠乳腺肿瘤病毒（MMTV）是一种B型逆转录病毒，可引起易感小鼠乳腺癌。该病毒通过喂养受感染的母乳传播给新生的幼崽，并导致派尔集合淋巴结中的B细胞的初始感染。与大多数逆转录病毒类似，MMTV感染和复制需要靶细胞处于激活状态。目前，激活初始B细胞靶群体的机制尚不清楚。Tlr-4蛋白是LPS信号转导途径的组成部分，其导致高水平的淋巴细胞活化。我们有初步证据表明MMTV Env蛋白与Tlr-4蛋白结合。LPS诱导的信号传导缺陷的C3 H/HeJ小鼠在LPS存在下表现出降低的MMTV毒力和降低的内源性MMTV基因表达。本工作的目的是了解小鼠乳腺肿瘤病毒（MMTV）Env和Tlr-4之间的分子相互作用，并确定Tlr-4介导的细胞活化在B细胞中MMTV发病早期阶段的作用。