RETROVIRAL REPRODUCTION PATHWAY

RETROVIRAL REPRODUCTION PATHWAY - RETROVIRAL REPRODUCTION...

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RETROVIRAL REPRODUCTION PATHWAY: Replication of the human retroviruses e.g., HIV starts with binding of the viral glycoprotein spikes (trimer of gp120 and gp41 molecules) to the primary receptor, the CD4 protein , and a second receptor, a 7- transmembrane G-protein-coupled chemokine receptor ( Figure 64-5 ). The co-receptor is either CCR5 , which is expressed on macrophages, peripheral, and other T cells (macrophages, [M]-tropic) or a different chemokine receptor ( CXCR4 ), which is expressed primarily on T cells (T- tropic) ( Figure 64-6 ). Chemokines are small peptides involved in promoting inflammatory responses and chemotaxis. A small percentage of people are resistant to infection because they have mutations in these co-receptors. Binding to the chemokine receptor brings the viral envelope and cell plasma membrane close together and allows the gp41 to interact with and promote the fusion of the two membranes. The fusion step is the target for an antiviral drug that interferes with the action of gp41. HIV can also bind to a cellular adhesion molecule, integrin alpha4beta 7, present on gut-associated lymphoid tissue. Once the genome is released into the cytoplasm, the early phase of replication begins. The reverse transcriptase, encoded by the pol gene, uses the tRNA in the virion as a primer and synthesizes a complementary , negative-strand DNA (cDNA). The reverse transcriptase also acts as a ribonuclease H, degrades the RNA genome, and then synthesizes the positive strand of DNA ( Figure 64-7 ). The reverse transcriptase is the major target for antiviral drugs. During the synthesis of the virion DNA (provirus) , sequences from each end of the genome (U3 and U5) are duplicated, thus attaching the LTRs to both ends. This process creates sequences necessary for integration and creates enhancer and promoter sequences within the LTR for the regulation of transcription . The DNA copy of the genome is larger than the original RNA Reverse transcriptase is very error prone . For example, the error rate for the reverse transcriptase from HIV is one error per 2000 bases, or approximately five errors per genome (HIV, 9000 base pairs), the equivalent of at least one typo on every page of this text but different for every book. This genetic instability of HIV is responsible for promoting the generation
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This note was uploaded on 04/29/2010 for the course BIOL 1404 taught by Professor Machaeldini during the Fall '09 term at Texas Tech.

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RETROVIRAL REPRODUCTION PATHWAY - RETROVIRAL REPRODUCTION...

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