A cDNA for a protein that interacts with the human immunodeficiency virus Tat transactivator

Article Abstract:

The human immunodeficiency virus (HIV) is unusual among retroviruses in that it requires the presence of both viral and cellular regulatory proteins to activate genes. One such factor is Tat, which interacts with specific viral gene sequences; the exact mechanism of this interaction is uncertain, largely because there is, as yet, no laboratory technique for modelling its function outside of living cells. Nevertheless, it has been hypothesized that Tat may interact with a cellular protein as a part of its regulatory role. Working on this hypothesis, researchers have now identified a human protein that interacts with the viral Tat protein. Large amounts of Tat were prepared by cloning the gene in bacteria, and then Tat was specifically labelled so that it could be visualized through a series of chemical reactions. This labelled Tat was incubated with a library of complementary DNA clones; the subsequent color development revealed that six clones, out of a total of two million, reacted with Tat. Further analysis revealed that the six clones represented actually two distinct genes, each of which had been independently isolated three times. This observation confirms that the assay for Tat binding is indeed highly specific; the protein was termed Tat-binding protein 1, or TBP-1. Experiments with infected cells revealed that TBP-1 suppressed the activation of genes by Tat. The results not only indicate an intracellular interaction, which may be of importance in understanding the workings of the AIDS virus, but also demonstrate a general method for the identification of other cellular molecules that may be involved in the regulation of viral replication. (Consumer Summary produced by Reliance Medical Information, Inc.)

Molecular biology, Molecular genetics, Antisense DNA

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Human CD4 binds immunoglobulins

Article Abstract:

CD4, a cell surface molecule found on T lymphocytes, has long been known to immunologists for its binding of the class II histocompatibility antigens. Recently, the same molecule has been recognized as the primary receptor for the AIDS virus. Researchers have now shown that the CD4 molecule seems to bind immunoglobulins as well. Immunoglobulins function as antibodies and exist in several classes and subclasses. Using relatively homogeneous human antibodies obtained from patients with myeloma, the investigators found that all classes of immunoglobulin bound to CD4. All subclasses bound with the exception of the IgG4 subclass, for which none of the six samples bound. Commonly, immunoglobulins bind to cells through their Fc portion, which is consistent among antibodies to different antigens. However, the binding of immunoglobulins to the CD4 molecule seems to take place on the Fab portion of the antibody, that portion which is variable, and binds antigen in a functioning molecule. The investigators discovered that the portion of the CD4 molecule that binds the antibody is close, but not identical, to the portion that binds the AIDS virus. The observation that CD4 binds to antibody molecules may help to explain why the AIDS virus can invade cells more effectively in the presence of antibodies than without antibodies. In addition, this new knowledge is critical to the design of any therapeutic regimen based on immunization or therapy with soluble CD4. (Consumer Summary produced by Reliance Medical Information, Inc.)

Immunoglobulins, T cells

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Enhancement of SIV infection with soluble receptor molecules

Article Abstract:

The human immunodeficiency virus type 1 (HIV-1) binds to a molecule called CD4 on its target cell in order to infect the cell, and some therapeutic approaches against AIDS (acquired immunodeficiency syndrome) are based upon the notion of providing plenty of free, soluble CD4 in the blood so that all the virus's receptors for CD4 are occupied. Other members of the immunodeficiency virus family, the simian immunodeficiency viruses (SIV) that have been isolated from monkeys, seem to bind to target cells in a similar way. However, experiments with SIVagm, an SIV found in African green monkeys, showed that soluble CD4 receptors actually enhance, rather than inhibit, the infection of cells. One possible explanation is that the SIVagm is capable of binding to other sites on the target cell in addition to CD4, and that filling up the virus with CD4 prior to infection induces other events, as yet unknown, which enhance the infectious process. Although the infectivity of the human virus, HIV, is definitely inhibited by soluble CD4, there is some evidence that HIV can infect some cells without CD4. This suggests that some secondary cell surface molecules may be involved in the sequence of events leading to infection with HIV or SIV. (Consumer Summary produced by Reliance Medical Information, Inc.)

Simian viruses

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