INTERACTIONS OF HUMAN RETROVIRUSES WITH HEMATOPOIETIC AND ADHERENT CELLS

人类逆转录病毒与造血细胞和贴壁细胞的相互作用

• 批准号: 3896343
• 负责人: F W RUSCETTI
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 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/3896343
• 关键词: AIDS; B lymphocyte; genetic transcription; human T cell leukemia; human T cell lymphotropic virus type 1; human immunodeficiency virus 1; human tissue; macrophage; messenger RNA; provirus; viral leukemogenesis; virus genetics; virus infection mechanism; virus receptors; virus replication

The human retroviruses, human immunodeficiency virus (HIV-1) and human tumor leukemia virus (HTLV-I), are involved in the pathogenesis of chronic, fatal human diseases. We have attempted to better understand the effects of host cell and other viruses on viral replication as well as the interaction between infected cells and the immune system. We have developed in I vitro models of viral latency for both HTLV-I and HIV-I. In HTLV-I infected B cells from acute T cell leukemia (ATL) patients, no viral mRNAs are being transcribed, yet integrated provirus is functional and can be activated to transform other T and B cells. When the virus infects T cells, the virus is expressed; when it infects B cells, it is not expressed. Also, the macrophage, a reservoir of HIV-I infection in acquired immunodeficiency syndrome (AIDS) patients, was shown to be able to restrict HIV-1 expression. THP-1, a macrophage cell line, was permissive for HIV-I expression. However, these infected cells become naturally non-productive for HIV 4-6 weeks after infection. Two classes of restricted HIV-I expression were seen: 1) low level which can be regulated by factors in the nuclei of infected cells and 2) no expression which may be due to methylation of the LTR. Both viruses make proteins which act in trans to positively regulate viral transcription. In these latently infected cultures, transactivation of viral transcription is inhibited. This indicates that the host factors play a role in this transcription and these cells either are deficient in positive regulators or possess negative regulators of viral transcription. Understanding the mechanisms of action of negative regulators of viral expression can be useful in developing anti-viral therapies.

人类逆转录病毒、人类免疫缺陷病毒（HIV-1）和人类免疫缺陷病毒（HIV-1）是人类免疫缺陷病毒（HIV-1）。 肿瘤白血病病毒（HTLV-I），参与慢性， 致命的人类疾病我们试图更好地了解 宿主细胞和其他病毒对病毒复制的影响以及相互作用 感染细胞和免疫系统之间的联系我们已经在体外开发了 HTLV-I和HIV-I的病毒潜伏期模型。在HTLV-I感染的B中 从急性T细胞白血病（ATL）患者的细胞中，没有病毒mRNA被 转录，但整合的前病毒是功能性的，可以被激活， 转化其他T和B细胞。当病毒感染T细胞时， 当它感染B细胞时，它不表达。还 巨噬细胞是获得性免疫缺陷患者HIV-1感染的宿主 综合征（艾滋病）患者，被证明能够限制HIV-1 表情THP-1是一种巨噬细胞系，对HIV-I是允许的 表情然而，这些受感染的细胞变得自然非生产性 HIV感染后4 - 6周。两类限制性HIV-I 表达：1）低水平，可由细胞因子调节， 感染细胞的细胞核和2）无表达，这可能是由于 LTR的甲基化。这两种病毒都能制造蛋白质， 正调控病毒转录。在这些潜伏感染的 在培养物中，病毒转录的反式激活被抑制。这 表明宿主因子在这种转录中起作用， 细胞要么缺乏正调节因子，要么具有负调节因子 病毒转录的调节因子。了解作用机制 病毒表达的负调节因子可以用于开发 抗病毒治疗。