INTERACTIONS OF HUMAN RETROVIRUSES WITH HEMATOPOIETIC AND ADHERENT CELLS

为了更好地了解宿主细胞和其他病毒对 病毒复制以及感染细胞之间的相互作用， 我们已经开发出病毒潜伏期的体外模型， 并限制HTLV-I和HIV-I的病毒表达。 在HTLV-I中 来自急性T细胞白血病（ATL）患者的感染的B细胞，非常少 病毒的mRNA被转录，但整合的前病毒是有功能的 并且可以被激活以转化其他T和B细胞。 当病毒 当病毒感染T细胞时，病毒被表达;当病毒感染B细胞时，病毒被表达。 表达得不好。 此外，巨噬细胞是HIV-I感染的宿主 在艾滋病患者中，显示能够限制HIV-1的表达。 巨噬细胞系THP-1允许HIV-1表达。 然而，这些受感染的细胞变得自然非生产性的艾滋病毒 4-6感染后几周。 两类限制性HIV-1表达 结果表明：（1）低水平，受核内因子调控 2）无表达，这可能是由于甲基化 的LTR。 这两种病毒都能产生反式的蛋白质， 调节病毒转录。 在这些潜伏感染的培养物中， 病毒转录的反式激活被抑制。 这表明 这些宿主细胞要么缺乏正调控因子， 具有病毒转录的负调节因子。 了解 病毒表达的负调节因子的作用机制可以是 可用于开发抗病毒疗法。 例如，我们发现 单核细胞慢性表达的负调节是由 通过抑制转录因子NF-kB与 HIV增强剂

To better understand the effects of host cells and other viruses on viral replication as well as the interaction between infected cells and the immune system we have developed in vitro models of viral latency, and restricted viral expression for both HTLV-I and HIV-I. In HTLV-I infected B cells from acute T cell leukemia (ATL) patients, very few 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 poorly expressed. Also, the macrophage, a reservoir of HIV-I infection in AIDS patients, was shown to be able to restrict HIV-I 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 these host 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. For instance, we have found that negative regulation of chronic expression in monocytes is mediated through inhibition of binding of the transcription factor, NF-kB to the HIV enhancer.