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HIV research - PHL116 Clinical Trials to test...

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PHL116 Clinical Trials to test Maternal-Fetal transmission of HIV I. The Science of Human Immunodeficiency Virus (HIV) & Acquired Immunodeficiency Syndrome (AIDS) [http://www.aegis.com] A. Pathogenesis 1. General Course of the Disease Infection with HIV leads to the gradual deterioration of immune system function if left untreated. HIV attacks, feeds off of, and disables CD4+ T-cells (white blood cells also known as helper T-cells or T-4 lymphocytes), which play a crucial role in the function of the immune system. In addition, there is an increase of suppressor T-cells or CD8+ lymphocytes with HIV infection. These cells attack and kill the infected cells implicated in the production of the virus. Healthy persons typically have 800-1,2000 CD4+ T-cells per cubic millimeter of blood. When a person’s T-cell count falls below 200 cells per cubic millimeter, the person moves from HIV+ status to full blown AIDS status, becoming susceptible to “opportunistic” infections [e.g., pneumonia, weight loss, diarrhea], brain dysfunction [e.g., dementia] and various cancers [Kaposi’s sarcoma and lymphomas]. 2. Disease Etiology -- Stages Human genes are made of deoxyribonucleic acid (DNA) and genes are located in the nuclei of cells. HIV is a retrovirus. Retroviruses have genes composed of ribonucleic acid (RNA) molecules. Stage 1 – Infection With HIV A person can become HIV infected by having unsafe sex or sharing needles with an HIV infected partner, or contamination with infected blood by means of blood transfusions. A mother can also pass HIV onto her baby in breast milk. HIV enters the body in particle form. Stage 2 – Fusion of HIV Particle and CD4+ Cell [also known as “helper T-cells”] HIV particles contain two copies of HIV RNA. Infection begins when an HIV particle encounters a CD4+ cell or T-cell. [HIV specifically attacks cells with CD4 molecules on their surfaces—while CD4+ cells are the main target, other immune system cells having CD4 molecules are also affected and scientists believe that even cells lacking CD4 molecules are also affected.] The membranes of the virus particle and the cell fuse together. [Different cells have different fusion cofactors.] Shortly following fusion, the virus’s RNA, proteins and enzymes are released into the cell. Stage 3 – Replication and Reverse Transcription HIV commandeers the CD4+ T-cell’s machinery. It replicates inside of the cell, in the cytoplasm, by means of an enzyme called reverse transcriptase. Reverse transcription is the enzymatic process by which HIV converts its RNA into DNA and incorporates it into the host cell’s genes. [AZT, ddC, ddI, D4T, 3TC and nevirapine are treatments designed to interfere with the conversion of RNA into DNA.] 1
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Stage 4: Integration Once reverse transcription occurs within a given cell, the HIV DNA takes over the cell’s nucleus, and is spliced into the host cell’s DNA by means of HIV integrase.
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