Lecture 20 - HIV and Antiretrovirals

Lecture 20 - HIV and Antiretrovirals - Lecture 20 HIV and...

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Lecture 20 - HIV and Antiretrovirals MI-42b. List the 3 essential retroviral genes and describe the function of the products of each of these genes - All the basic retroviral gene – 2 long terminal repeats o gag – internal structure gene; encodes the core proteins (group-specific antigens) o pol – the gene for reverse transcriptase (polymerase) o env – envelope gene (glycoproteins that form projections of the envelope) - All the transcript that was translated by this provirus and was done in different splicing mechanisms MI-42a. Describe the important components of the HIV virion , the essentials of the HIV replicative cycle , and viral latency . Describe how these components relate to the strategies of antiretroviral treatment MI-42c. Define clade and describe how it relates to the epidemiology of HIV infections HIV = retrovirus -- VIRION Enveloped viruses (80 to 100 nm diameter) GENOME: Negative polarity RNA genome (have to carry polymerase) Postive sense 7 to 12 kb, single-stranded , non-segmented Two-copies per virion (“diploid”) critical for reverse transcriptase step (countable for the high recombinant form) unique from other retrovirus: cylindrical core for the virion Replicative strategy: reverse transcription to generate double stranded DNA followed by integration of genome into the host genome. this is different than the classic DNA RNA Protein the viral genomic RNA is reverse transcribed and integrated double stranded DNA to host genome goes through the same step as host genome replication The viruses: The Human Retroviruses Oncogenic retroviruses (transforming) Lentiviruses (cytopathic; cause immunodeficiency) – slow virus HTLV-I (human T-cell leukemia – lymphotropic virus) – Japan, Africa, the East Coast of S America Infects and transforms T cells but is not cytolytic Transmitted vertically via breast milk . Also via exchange of blood (including transfusion and IVDU) and sexually . Adult T-cell leukemia/lymphoma (ATL- Caribbean); Tropical spastic paraperesis (TSP – Japan) Frequency of development of disease is low (3-5% for ATL, <3% for TSP) incubation period of 20 to 30 years or more for ATL can be much shorter (months) for TSP. Findings of ATL include: large numbers of ATL cells (lymphocytes with lobulated or cleaved nuclei), skin lesions (redness or tumor infiltration into skin) lymphadenopathy hepatosplenomegaly Survival typically months to several years Tropical spastic paraperesis (TSP); HTLV-1 associated myelopathy (HAM) Demyelination of long motor neurons in spinal cord Characterized by stiff gait progressing to increasing spasticity Lower extremity weakness Urinary incontinence Sensory neuropathy Hyperreflexia Therapy for HTLV-1 related disease ATL: cytotoxic chemotherapy including steroids TSP/HAM: Cortico- or androgenic steroids
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This note was uploaded on 09/14/2011 for the course PHARM mb taught by Professor Staff during the Spring '11 term at UCSD.

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Lecture 20 - HIV and Antiretrovirals - Lecture 20 HIV and...

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