Phosphorothioate oligodeoxycytidine interferes with binding of HIV-1 gp120 to CD4
Article Abstract:
Phosphorothioate oligodeoxynucleotides, a class of oligodeoxynucleotide, have been found to be effective suppressors of the multiplication of the human immunodeficiency virus (HIV). The site at which this inhibitory action occurs is not known, especially since reports on the rate of uptake of phosphorothioate oligomers by cells show that uptake is usually insufficient for this purpose. Therefore, other sites outside the cell may be involved in the ability of phosphorothioate oligodeoxynucleotides to reduce HIV-related injury to cells. The present study investigated the role of phosphorothioate oligodeoxycytidine in the binding of glycoprotein (gp) 120, a viral protein of HIV cells, to the surface of CD4 cells. HIV transmission is thought to occur when gp120 binds to CD4 on the surface of uninfected cells. Phosphorothioate oligodeoxycytidine was hypothesized to partially interfere with the ability of HIV to bind to other cells, and therefore this would disrupt HIV replication. In order to study this relationship, the formation of syncytium was measured. Syncytium is a mass that forms when cells join (that is, when gp120 and CD4 proteins of two cells bind) as a result of the action of HIV. Such joining allows the cell-to-cell transmission of virus and may account for the death of cells. Oligodeoxynucleotides were shown to be effective in blocking syncytium formation at specific concentrations; they also interfered with the binding of gp120 to the CD4 protein on cell surfaces. It is therefore suggested that phosphorothioate oligodeoxynucleotide binds to CD4, interfering with the binding of gp120 to the CD4. In this way, the phosphorothioate oligodeoxynucleotides may protect healthy cells from HIV infection. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Journal of Acquired Immune Deficiency Syndromes
Subject: Health
ISSN: 0894-9255
Year: 1991
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HIV DNA integration: observations and inferences
Article Abstract:
Retroviruses, including HIV (human immunodeficiency virus) and HTLV (human T-lymphotropic virus) must integrate, or join, in the human genome for replication of the virus to occur. Two parts of the virus are necessary for integration: sequences known as LTRs, long terminal repeats, which join to the host DNA; and the integration protein (IN), which is thought to bind to and cleave DNA and may be involved in the transportation of the viral DNA to the nucleus of the cell, where integration occurs. The virus can integrate into many sites in the host DNA. Integration of the virus may result in the inactivation, the enhanced expression, or the transduction (movement from one site on a chromosome to another) of genes adjacent to the site of integration. When the virus integrates next to an oncogene (cancer-causing gene), cell transformation or uncontrolled growth can occur. Studies have shown that the virus integrates preferably into sites that are being transcribed, one of the processes necessary for the expression of proteins from DNA. Since integration is essential for replication of the virus, the inhibition of this process is an objective of antiviral therapy. There is a search for compounds that inhibit viral integration. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Journal of Acquired Immune Deficiency Syndromes
Subject: Health
ISSN: 0894-9255
Year: 1990
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HIV protease inhibitors: their anti-HIV activity and potential role in treatment
Article Abstract:
Protease inhibitors may be useful in treating human immunodeficiency virus (HIV) infection. Most efforts to treat HIV infection have focused on drugs such as zidovudine (ZDV) that inhibit DNA synthesis in the virus. ZDV, however, appears to lose its effectiveness after the first year of treatment and can be toxic. HIV falls into the category of viruses that produce their own proteases, increasing their ability to infect various types of cells. Immature virus particles cannot infect other cells, and proteases are necessary for the maturation of the virus. Laboratory experiments with protease inhibitors suggest that the inhibitors may selectively prevent virus maturation with little effect on normal cell function. Therapies combining protease inhibitors with drugs such as ZDV may prove to be both safer and more effective in treating HIV and in preventing the development of HIV strains that are resistant to treatment.
Publication Name: Journal of Acquired Immune Deficiency Syndromes
Subject: Health
ISSN: 0894-9255
Year: 1993
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