INTERACTIONS OF HUMAN RETROVIRUSES WITH HEMATOPOIETIC AND ADHERENT CELLS

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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.