BIOL 3440 Quiz: Unit 1 Study Guide

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BIOL 3440
Matthew S.Grober 

Unit 1 I. Chapter 1 A. What is HIV? 1. Intracellular parasite incapable of reproducing on its own 2. Invades specific types of cells in the human immune system a. Hijacks the enzymatic machinery, chemical materials, and energy of the host cells to make copies of itself and killing the host cells in the process 3. Life cycle a. Extracellular phase i. Infectious phase ii. Virus moves from one host cell to another and can be transmitted from host to host iii. Extracellular form called a virion or virus particle b. Interacellular phase i. Replication phase ii. Latches onto 2 proteins on the surface of a host cell iii. Adhere to CD4 and then attaches to a 2 protein called a coreceptor iv. Fusion of the virion’s envelope and spills contents into cell • Contents include genome (2 copies of single stranded RNA) • 2 viral enzymes- reverse transcriptase and integrase (splices its DNA genome into host cell genome) v. Host cell’s RNA polymerase transcribes viral genome into viral mRNA vi. Synthesize viral proteins vii. Virions assemble and bud off viii. New virions- HIV protease enzyme cleaves precursors of various viral proteins into functional forms allowing virion to mature ix. New virions are ready to invade more cells 4. Difficult to treat because HIV uses host cell’s polymerases, ribosomes, and tRNAs 5. Hard to find drugs to disrupt viral life cycle and not host life cycle 6. Antiviral drugs target enzymes from virions, reverse transcriptase and integrase B. How Does the Immune System React to HIV? 1. Dendritic cells patrol different tissues 2. Dendritic cell captures a virus, travels to a lymph node or other lymphoid tissue 3. Presents virus parts to white blood cell, naïve helper T cells 4. Naïve helper T cells carry T-cell receptors 5. Dendritic cell presents virus parts to T cell receptor, helper T cell activates 6. Grows and divides producing effector helper T cells 7. Effector helper T cells release cytokines to mobilize immune cells to fight 8. Induce B cells to mature into plasma cells which produce antibodies that bind to virions and mark them for elimination 9. B cells activate killer T cells and recruit macrophages to destroy infected host cells 10. Few effector helper T cells become memory helper T cells C. How Does HIV Cause AIDS? 1. HIV latches onto 2 proteins a. CD4 b. Coreceptor i. Different strains of HIV exploit different coreceptors ii. Most use CCR5 2. Cells that carry both CD4 and CCR5 more most vulnerable 3. Acute phase a. HIV virions enter host body and replicate b. Concentration of virions increase c. Concentration of CD4 T cell decrease d. Acute ends when viral replication slows and concentration of virions drops e. CD4 T-cell count recover 4. Chronic phase a. Few symptoms b. HIV continues to replicate c. Concentration of virions rises again and CD4 T cells fall 5. AIDS phase a. Concentration of CD4 T cells drops below 200 cells per cubic millimeter b. Immune system collapse and cannot fend off opportunistic infections 6. HIV to AIDS a. HIV attack CD4 T cells in gut- destroys a large fraction of helper T cells and damages other tissues allowing barrier between gut bacteria and bloodstream to meet b. Weakening of barrier lets bacteria move into the blood, high level of activation in the immune system c. Chronic infection and inflammation of lymph nodes irreversibly exhausts the immune system’s capacity to generate new T cells d. As T cell concentration falls the body is unable to fight against other infections D. Why Does HIV Therapy Using Just One Drug Ultimately Fail? 1. Vaccine for potential targets- protease, integrase, and reverse transcriptase 2. AZT interferes with reverse transcriptase a. Similar chemical structure to thymidine b. Fools reverse transcriptase into picking it up and incorporating it into new DNA strand c. Thymidine has OH group and AZT has azide group i. Hydroxyl group allows more nucleotides to be added ii. AZT has no hydroxyl group so reverse transcriptase is stuck iii. AZT disrupts pathway 3. Reverse transcriptase a. Uses virus’s RNA to make a complementary strand of viral DNA E. Does AZT Alter the Patient’s Physiology? 1. Lose effectiveness a. Patient’s cellular physiology could change F. Does AZT Alter the Population of Virions Living in the Patient? 1. Virions could change themselves to be resistant 2. Populations evolve G. What Makes HIV Resistant to AZT? 1. Resistant virus 2. Susceptible virus 3. Reverse transcriptases become less likely to mistake AZT or more likely to remove AZT after insertion- able to continue replicating 4. Change in viral strains- have some ability to correct transcription errors, reverse transcriptase is prone to mistakes a. Variant mutant will continue to replicate b. Variant mutant will keep replicating until the population is mostly resistant to AZT c. Evolution by natural selection- change over time in the composition of the viral population H. Evolution by Natural Selection 1. 4 steps a. Replication errors produce mutation in the reverse transcriptase gene. Virions carrying different reverse transcriptase genes produce version of the reverse transcriptase enzyme that vary in their resistance to AZT. b. The mutant virions pass their reverse transcriptase genes, and thus their AZT resistance or susceptibility, to their offspring. In other words, AZT resistance is heritable. c. During treatment with AZT, some virions are better able to survive and reproduce than others. d. The virions that persist in the presence of AZT are the ones with mutations in their reverse transcriptase genes that confer resistance. 2. Composition of viral composition changes over time 3. Virions resistant to AZT large fraction and virions susceptible to AZT become rare 4. Natural selection just happens can happen to any population in which the 4 steps occur a. Can happen in any population in which there are heritable variation in reproductive success I. Understanding Evolution Helps Researchers Design Better Therapies 1. Categories of drugs in use intended for disruption a. Coreceptor inhibitors- bar HIV from entering host cells in the first place by preventing them from latching onto the host cell’s CCR5 molecules b. Fusion inhibitors- bar HIV from entering host cells by interfering with HIV’s gp120 or gp41 proteins c. Reverse transcriptase inhibitors- inhibit reverse transcriptase by mimicking the normal building blocks of DNA; others inhibit reverse transcriptase by interfering with the enzyme’s active site d. Integrase inhibitors- block HIV’s integrase from inserting HIV’s DNA into the host genome, preventing the transcription of new viral RNAs e. Protease inhibitors- prevent HIV’s protease enzyme from cleaving viral precursor proteins to produce mature components for new virions 2. Antiretroviral drugs used alone, outcome will be the same as AZT- evolves resistance 3. Need strategy to reduce genetic variation for resistance- use 2 or more drugs at once a. Highly active antiretroviral therapy or HAART J. The Evolution of HIV Strains Resistant to Multiple Drugs 1. Patients who took few of their doses subjected their HIV populations to weak selection 2. Patients who took all their does shut down virtually all viral replication 3. Patients who took most, but not all, of their doses subjected their HIV populations to strong selection, but allowed some viral replication, thus creating permissive conditions for evolution K. Shortsighted Evolution? 1. Epitopes- short pieces of viral protein displayed on the surface of the virion or the infected cell 2. Evolution of HIV population contributes to the death of the host i. Continuous evolution toward novel epitopes enables the viral population to stay far enough ahead of the immune response to avoid elimination ii. Viral population within many hosts evolves toward ever more aggressive replication iii. In at least half of all hosts, strains of HIV evolve that can infect naïve T cells 3. Virions do not look to the future and anticipate that as their population evolves, it will ultimately kill its host II. Chapter 3 A. III. Chapter 4 A. How to read an evolutionary tree 1. Evolutionary tree, phylogenetic tree, phylogeney- diagram showing th
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