First rt acts as an rna dependent dna polymerase

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• First, RT acts as an RNA-Dependent DNA Polymerase (Reverse Transcriptase Activity) and... - RT synthesizes Negative Sense Strand DNA using the Positive Sense RNA Genome as Template • tRNA serves as Primer • RT simultaneously acts as an RNA Nuclease (RNase Activity) and... - RT degrades almost all of the RNA Genome • A small RNA Oligomer of the Genome remains intact • Finally, RT acts as a DNA-Dependent DNA Polymerase and... - RT synthesizes Positive Sense DNA Strand using the newly synthesized Negative Sense DNA as a Template • The small RNA Oligomer remaining from the Genome serves as Primer Double-Stranded DNA, MA and IN are associated in a Preintegration Complex • Preintegration Complex is transported into the Nucleus via Nuclear Pores HIV DNA integrates into the Host Genome • Integration requires IN - Integration is a required Step in HIV Replication • Integrated HIV DNA is termed a Provirus - Provirus is a stable Genetic Element in the Host Genome The Provirus is replicated whenever the Chromosome is replicated. As with Insertion Sequences and Transposons, Integration generates a Direct Repeat of Host DNA Target Sequences on either Side of the Provirus.
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HIV/AIDS Page 8 HIV mRNA • Host RNA Pol II obligingly transcribes Provirus DNA producing more than 25 different mRNAs that fall into Three Categories: - 2 Kb Spliced for Regulatory Proteins - 4 Kb Spliced for Env Proteins - 9 Kb Unspliced for Gag and Gag-Pol Polyproteins HIV Protein Synthesis HIV Proteins -- like Polio Virus Proteins -- are initially produced as Env Polyprotein, Gag Polyprotein and Gag-Pol Polyproteins • 4 Kb Spliced mRNA for Env Proteins targets Rough Endoplasmic Reticulum • Env Polyprotein is synthesized on (i.e. extruded into) RER and transported to the Cell Membrane - Glycosylated and cleaved during Transit by Host Cell Enzymes into SU and TM - Form Patches of SU/TM Trimers on the Cell Membrane • 9 Kb Unspliced mRNA for Gag and Gag-Pol Polyproteins targets “Free” Ribosomes in the Cytoplasm • Gag and Gag-Pol Polyproteins are made on cytoplasmic Ribosomes - Approximately 20 Times more Gag Polyprotein is synthesized than is Gag-Pol Polyprotein The Gag and Pol Polyproteins are (1) Separated by a single Stop Codon, and (2) Read in different Reading Frames. The Frameshift occurs when the Ribosome reaches a Heptamer Sequence (U UUU UUA) and a Stem-Loop which occasionally shifts the Reading Frame back by one Nucleotide such that the Ribosome will no longer recognize the Stop Codon. But this doesn ʼ t happen very often so there ʼ s about 20 Times more Gag Polyprotein than there is Gag-Pol Polyprotein. - Gag and Gag-Pol Polyproteins will not be cleaved into Capsid Proteins and Enzymes by until PR becomes activated during HIV Maturation following Budding HIV Genome Synthesis Host RNA Pol II obligingly transcribes Provirus DNA producing -- • Full length Transcripts that serve as HIV Genome
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HIV/AIDS Page 9 HIV Assembly into Immature Virus Particles
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