Ljubljana/glossary

From 2007.igem.org

Company Name

Glossary

AIDS - Acquired immune deficiency syndrome is a collection of symptoms and infections resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV) in humans. The late stage of the condition leaves individuals susceptible to opportunistic infections and tumors.

Apoptosis - is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death and involves an orchestrated series of biochemical events leading to a characteristic cell morphology and death.

Capsid - is the protective shell of protein that surrounds the genetic material of a virus.

CCR5 - short for chemokine (C-C motif) receptor 5. CCR5 is predominantly expressed on T cells, macrophages, dendritic cells and microglia. HIV uses CCR5 or another protein, CXCR4, as a co-receptor to enter its target cells. CCR5 is likely the most physiologically important coreceptor during natural infection.

CD4 - CD4 (cluster of differentiation 4) is a glycoprotein expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages, and dendritic cells. Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily. CD4 is also a primary receptor used by HIV-1 to gain entry into host T cells.

CXCR4 - also called fusin, this is one of two co receptors for HIV binding to the human cell, it is embedded in the T Cell membrane. The other co receptor is CCR5.

Env - The envelope gene encodes the surface glycoprotein (SU) - transmembrane (TM) polyprotein. Env gene is located in the HIV genome.

Gag - The gag (group specific antigen) gene encodes the viral matrix (MA) capsid (CA) and nucleoproteins (NC). Gag gene is located in the HIV genome.

GFP - protein, comprised of 238 amino acids (26,9 kDa), originally isolated from the jellyfish. When GFP is exposed to blue light it fluoresces green and is therefore easy to detect on confocal microscope.

gp41 - is a glycoprotein non-covalently bound to gp120, and provides the second step by which HIV enters the cell. It is originally buried within the viral envelope, but when gp120 binds to a CD4 receptor, gp120 changes its conformation causing gp41 to become exposed, where it can assist in fusion with the host cell.

gp120 - is a glycoprotein exposed on the surface of the HIV envelope. The glycoprotein gp120 is anchored to the viral membrane through non-covalent bonds along with gp41, both coming from a cleaved protein, gp160. It infects any target cell with a CD4 receptor, particularly the helper T-cell, by binding to that receptor.

HAART - Highly Active AntiRetroviral Therapy. Treatment for human immunodeficiency virus (HIV) infection that uses a combination of several antiretroviral drugs. The drugs inhibit the ability of the virus to multiply in the body, and they slow down the development of AIDS.

HIV - Human immunodeficiency virus is a retrovirus that can lead to acquired immunodeficiency syndrome (AIDS). HIV infection leads to a progressive reduction in the number of T cells possessing CD4 receptors.

HIV protease - aspartyl protease that is essential for the life-cycle of HIV. Inhibition of this protease prevents maturation of HIV particles. As such, many drugs have been developed (protease inhibitors) that target this enzyme.

Integrase - an enzyme produced by a retrovirus (including HIV) that enables its genetic material to be integrated into the DNA of the infected cell. It is also produced by viruses containing double stranded DNAs for the same purpose.

LTR - long terminal repeats (LTRs) are found in retroviral DNA flanking functional genes. The LTRs are partially transcribed into an RNA intermediate, followed by reverse transcription into complementary DNA (cDNA) and ultimately dsDNA (double-stranded DNA) with full LTRs. The LTRs then mediate integration of the retroviral DNA via an LTR specific transposase called integrase into another region of the chromosome. This is the basic mechanism used by HIV. LTRs also act as promoters/enhancers - when integrated into the host genome they influence the cell machinery which transcribes DNA to alter the amount of transcription which occurs

NRTI - analogs of nucleosides/nucleotides (building blocks necessary for DNA synthesis). They inhibit the reverse transcriptase of HIV, thus inhibiting its replication and leading to decreased viral loads.

NNRTI - non-nucleoside reverse transcriptase inhibitors, a family of reverse transcriptase inhibitors used as anti AIDS treatment.

Polyprotein - protein that is cleaved after translation to produce several functionally distinct proteins.

Pol - encodes the reverse transcriptase (RT) and an integrase (IN). Pol gene is located in the HIV genome.

Retrovirus - is any virus belonging to the viral family Retroviridae. They are enveloped viruses possessing a RNA genome and replicate via DNA intermediate. Retroviruses rely on the enzyme reverse transcriptase to perform the reverse transcription of its genome from RNA into DNA, which can then be integrated into the host's genome with an integrase enzyme. The virus then replicates as part of the cell's DNA.

Split protein system - Experimental procedure to detect protein-protein interactions that uses two fusion proteins (“hybrids”) which reconstitute an active transcription factor (or some other active protein) when the two fusion proteins interact.

T-cells - belong to a group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity. They attack virus-infected cells, foreign cells and cancer cells. T-cells also produce a number of substances that regulate the immune response.

T7 RNA polymerase - catalyzes the formation of RNA in the 5'→ 3' direction. T7 RNA polymerase is extremely promoter-specific and only transcribes bacteriophage T7 DNA or DNA cloned downstream of a T7 promoter.

TEV protease - highly site-specific protease that is found in the Tobacco Etch Virus (TEV). It is a cysteine protease. Advantages of this enzyme are its high specificity and its high activity rate.

Ubiquitin - highly conserved small regulatory protein that is ubiquitous in eukaryotes. Ubiquitination refers to the post-translational modification of a protein by the covalent attachment (via an isopeptide bond) of one or more ubiquitin monomers. The most prominent function of ubiquitin is labeling proteins for proteasomal degradation.


References

Drugs Used in the Treatment of HIV Infection. 2007. FDA.
http://www.fda.gov/oashi/aids/virals.html (October 2007)

Heckman K.L., Pease L.P. 2007. Gene splicing and mutagenesis by PCR-driven overlap Extension.
Nature Protocols, 2, 4: 924-932

Johnsson N., Varshavsky A. 1994. Split ubiquitin as a sensor of protein interactions in vivo.
Proceedings of the National Academy of Sciences, 91: 10340–10344

Lieber A., Kiessling U., Strauss M. 1989. High level gene expression in mammalian cells by a nuclear T7-phage RNA polymerase.
Nucleic Acids Research, 17, 21: 8485-8493

Stagljar I., Fields S. 2002. Analysis of membrane protein interactions using yeast-based technologies.
TRENDS in Biochemical Sciences, 27, 11: 559-563

Vocero-Akbani A.M., Heyden N.V., Lissy N.A., Ratner L., Dowdy S.F. 1999. Killing HIV-infected cells by transduction with an HIV protease-activated caspase-3 protein.
Nature Medicine, 5, 1: 29-33

Wehr M.C., Laage R., Bolz U., Fischer T.M., Grunewald S., Scheek S., Bach A., Nave K.A., Rossner M.J. 2006. Monitoring regulated protein-protein interactions using split TEV.
Nature Methods, 3, 12: 985-993