The Uses of HTS Assays

Storing, processing, analyzing, and accessing the wealth of data generated in an HTS assay poses special problems, simply because there is so much of it. Bioinformatics strategies are used to develop databases relating chemical structure, target characteristics, and assay results, allowing researchers to learn more from their results than just whether or not a particular compound was successful. Analyzing the common features of successful compounds may lead to rational development of better drug candidates.

High-throughput technology can also be put to use in other areas besides drug development. Indeed, any system in which there are many similar candidates to be screened, and in which a visible output can be designed, is genomics study of amenable to high-throughput methods. Genomics applications are a prin-

gene sequences cipal area for applying HTS technology, in DNA sequencing, protein analy sis, and other fields. HTS methods can be combined with DNA microarray technology, for instance, to analyze the expression of hundreds of different genes under varying conditions. see also Bioinformatics; Biotechnology; Combinatorial Chemistry; DNA Microarrays; Proteomics.

Richard Robinson


Brush, Michael. "High-Throughput Technology Picks Up Steam." Scientist 13, no. 4 (February 15, 1999): 11.

Internet Resource

High Throughput Screening. <>.

HIV, the human immunodeficiency virus, is the virus that causes AIDS, a debilitating and deadly disease of the human immune system. HIV is one of the world's most serious health problems: at the end of 2001, more than 40 million people worldwide were infected with HIV and living with the virus or AIDS. The World Health Organization estimates that about 20 million people have died from AIDS since the infection was first described in 1981. Nearly 500,000 of those deaths have occurred in the United States. Although there is no cure for the disease, therapies exist that reduce the

The HIV virion (virus particle) has two glycoproteins on the outside, which aid its passage into human cells. It contains two copies of its RNA genome, plus the reverse transcriptase enzyme used to copy the RNA into DNA once it is inside the host cell.


symptoms of AIDS and can extend the life spans of HIV-infected individuals. Researchers are also pursuing protective vaccines, but a reliable vaccine might still require years to develop.


HIV infects certain cells and tissues of the human immune system and takes them out of commission, rendering a person susceptible to a variety of infections and cancers. These infections are caused by so-called opportunistic agents, pathogens that take advantage of the compromised immune system but that would be unable to cause infection in people with a healthy immune system. Rare cancers such as Kaposi's sarcoma also take hold in HIV-infected individuals. The collection of diseases that arise because of HIV infection is called acquired immune deficiency syndrome, or AIDS. HIV is classified as a lentivirus ("lenti" means "slow") because the virus takes a long time to produce symptoms in an infected individual.

HIV Life Cycle: Entering Cells

Like a typical virus, HIV infects a cell and appropriates the host's cellular components and machinery to make many copies of itself. The new viruses then break out of the cell and infect other cells. HIV stores its genetic information on an RNA molecule rather than a DNA chromosome. This is a distinguishing characteristic of retroviruses, which are viruses that must first convert their RNA genomes into DNA before they can reproduce.

Each HIV virion (viral particle) is a small sphere composed of several layers. The external layer is a membrane coat, or envelope, obtained from the host cell in which the particle was made. Underneath this membrane lies pathogens disease-causing organisms retroviruses RNA-containing viruses whose genomes are copied into DNA by the enzyme reverse tran-


HIV's gp120 protein interacts with two proteins on the surface of the target cell. Gp41 then promotes fusion of the virus membrane with the cell membrane, allowing the viral contents to enter the cell. Adapted from an article in Molecular Medicine Today, 1998.

antibodies immune-system proteins that bind to foreign molecules a shell made from proteins, called a nucleocapsid. Inside the protein shell are two copies of the virion's RNA genome and three kinds of proteins, which are used by the virion to establish itself once inside the cell that it infects.

Two proteins, called gp120 and gp41, enable the virion to recognize the type of cell to enter. These proteins project from the HIV membrane coat. Gp120 binds to two specific proteins found on the target cell's surface (these target-cell proteins are called receptors). The first receptor, CD4, is found on immune system cells known as CD4 T cells, and also sometimes on two cell types known as macrophages and dendritic cells. The immune system uses CD4 T cells in the initial step in making antibodies against infectious agents. After binding to CD4, the HIV protein called gp120 binds with a second cell membrane protein, commonly referred to as the co-receptor. The co-receptor can be one of many different proteins, depending on the cell type. The two most common are CXCR4, which is normally found on CD4 T cells, and CCR5, a receptor found on CD4 T cells as well as on certain macrophages and dendritic cells. In the absence of HIV, CXCR4 and CCR5 allow these immune system cells to respond to chemical signals, but when HIV infects the cells, the HIV commandeers their usage. In some cases, individuals have a mutation in their co-receptor that prevents HIV from entering their cells.

Once gp120 has bound to both the CD4 receptor and co-receptor, the gp41 protein fuses HIV's membrane envelope with the cellular membrane, injecting the virus into the target cell. Once in the cytoplasm, the viral protein shell opens up and releases the viral proteins—a reverse transcriptase, a viral integrase, and a protease—along with the viral RNA strands. The reverse transcriptase copies the RNA strands into DNA. The viral integrase then helps insert the DNA copies into the cell's chromosome. At this point, the virus is called a provirus, and the life cycle halts. The provirus may remain dormant in the cell's chromosome for months or years, waiting for the T cell to become activated by the immune system.

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