CMV INDUCTION OF TUMOR NECROSIS FACTOR (TNF ALPHA) IN INFECTED TISSUE

CMV 在感染组织中诱导肿瘤坏死因子 (TNF ALPHA)

• 批准号: 3804801
• 负责人: J F MANISCHEWITZ
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3804801
• 关键词: AIDS; HIV infections; colitis; cytomegalovirus; human immunodeficiency virus 1; human subject; human tissue; in situ hybridization; inflammation; intestinal mucosa; latent virus infection; messenger RNA; monocyte; nucleic acid probes; opportunistic infections; provirus; tumor necrosis factor alpha

CMV is a major cause of inflammatory organ disease in immunosuppressed patients. To elucidate the mechanisms of CMV-induced inflammation, tumor necrosis factor alpha (TNF alpha) was studied in AIDS patients with CMV colitis. In Situ hybridization techniques were used on colonic mucosa from AIDS patients and normal controls. Positive hybridization of TNF alpha probe to mRNA was obtained with colonic mucosa from patients, and was associated with CMV but not HIV-1 infected cells. Also, a patient- derived isolate of CMV induced primary human blood monocytes to express TNF-alpha mRNA and increased the levels of secreted TNF-alpha. Thus, CMV induction of TNF-alpha may play a central role in CMV-induced inflammation. Furthermore, because of the known effects of TNF-alpha on the expression of HIV-1 provirus, CMV may be a co-factor in activation of latent HIV-1, without a requirement for co-infection of cells by the two viruses.

巨细胞病毒是免疫抑制的炎症性器官疾病的主要原因 患者为了阐明巨细胞病毒引起炎症、肿瘤的机制， 研究了艾滋病合并巨细胞病毒（CMV）患者的坏死因子α（TNF α） 结肠炎 原位杂交技术应用于结肠粘膜 艾滋病患者和正常对照组。 TNF阳性杂交 从患者的结肠粘膜获得mRNA的α探针， 与CMV感染细胞相关，但与HIV-1感染细胞无关。 还有一个病人 CMV衍生分离物诱导原代人血单核细胞表达 TNF-α mRNA的表达，并增加分泌的TNF-α的水平。 因此，CMV TNF-α的诱导可能在CMV诱导的细胞凋亡中起重要作用。 炎症 此外，由于TNF-α对肿瘤细胞的已知作用， HIV-1前病毒CMV的表达可能是激活HIV-1感染的辅助因子， 潜伏的HIV-1，不需要两种病毒共同感染细胞 病毒