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Lecture

Chapter 1- Understanding HIV

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Department
Biology
Course Code
BIOL-1005
Professor
Human Resource Mgmt

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Chapter 1- Understanding HIV Why study evolution? o The tools and techniques of evolutionary biology offer crucial insights into matters of life and death Human Immunodeficiency Virus (HIV) causes Acquired Immune Deficiency Syndrome (AIDS) o HIV is an emerging virus, it rapidly evolves drug resistance and it is deadly Evolutionary biology is the science devoted to understanding two things: o How populations change through time following modifications in their environment o How new species come into being 1.1- The Natural History of the HIV/AIDS Epidemic List of worst epidemic in human history according to the number of deaths: o Influenza-50 to 100 million deaths-across the globe o Black Death (1347-1352)-took 30%-50% of the European population-about25 million lives o New World small pox-released in 1520 by European conquistadores-decimated Native American populations across two continents AIDS is among the worst epidemics in human history o Was first recognized in 1981 o So far infected more than 65 million people o 25 million have already died o By year 2020, a total of 90 million lives would have been claimed by AIDS o According to World Health Organization, AIDS is responsible for about 4.9% of all deaths worldwide o Sub-Saharan Africa is mostly affected by this epidemic HIV establishes a new infection when a bodily fluid holding the virus, usually a blood or semen, carries it from an infected person directly onto a mucous membrane or into the bloodstream of an uninfected person o Can be passed during heterosexual sex, homosexual sex, oral sex, needle sharing, transfusion with contaminated blood products, childbirth, and breastfeeding An HIV infection can be acquired only from someone else who already has it! What is HIV? Like all viruses, HIV is an intracellular parasite that cannot reproduce on its own o It invades specific types of cells in the human immune system o It uses enzymatic machinery and energy of these cells to make copies of itself, killing the host cells in the process Figure 1.5 (Pg. 7) contains the life cycle of HIV in detail. o The life cycle includes an extracellular phase and an intracellular phase o During the extracellular phase, the virus moves from one host cell to another, and can be transmitted from host to host o Extracellular form of a virus is called a virion, or virus particle o During intracellular or parasitic phase, the virus replicates HIV initiates its replication phase by latching onto two proteins on the surface of a host cell HIV binds to two surface proteins on the target cell called CD4 and coreceptor This binding fuses the virions envelope with the hosts cell membrane and spills the contents of the virion into the cell These contents include the viruss diploid genome (two copies of a single-stranded RNA molecule) and 3 proteins: o Reverse transcriptase- transcribes the viruss RNA genome into DNA o Integrase- splices the DNA genome into the host cells genome o Protease- which plays a role in the preparation of new viral proteins In HIV and other retroviruses, flow of genetic information is different than in cells and in viruses with DNA genomes In retroviruses, genetic information does not follow the familiar route from DNA to mRNA to proteins o Instead it flows from RNA to DNA, then to mRNA to proteins Once HIVs genome is inserted into the host cells chromosomes, the host cells RNA polymerase transcribes the viral genome into mRNA, and the host cells ribosomes synthesize viral proteins New virions assemble in the host cell cytoplasm, then bud off the cell membrane and enter the bloodstream There, the new virions may find another cell to infect in the same host, or be transported to a new hosto Significant feature of HIVs life cycle is that the virus uses the host cells own enzymatic machinery, its polymerases, ribosomes, and tRNAs in almost every step How Does HIV Cause AIDS? HIV parasitizes immune system cells, particularly helper T cells. After a long battle against the virus, the immune systems supply of helper T cells is badly depleted. Because helper T cells play a crucial role in the response to invading pathogens, this leaves the host vulnerable to a variety of secondary infections. Through research on how SIVsm (simian immunodeficiency virus) in monkeys, it was concluded that the hosts own immune response contributes to the development of immunodeficiency o Human HIV patients treated with antiretroviral drugs plus the immunosuppressant cyclosporine maintained higher helper T cell counts than control patients treated with antiretrovirals alone T cells derive from stem cells in the bone marrow These stem cells generate precursors that mature into naive T cells in the thymus Naive T cells are activated in lymph nodes An activated T cell undergoes a burst of proliferation, yielding effector and memory cells o These circulate in the blood and move through tissues A large fraction of the bodys memory cells reside in lymphoid tissue associated with mucus membranes lining the nose, mouth, lungs, and especially the gut Naive T cells and memory T cells are long lived o But effector cells, which actively engage in the fight against invaders, are short lived Any given T cell lineage has a finite capacity for replication-a capacity that is reduced with each cell division o So with each burst of replication within a T cell lineage brings that lineage closer to exhaustion Sustained immune activation during HIV infection can ultimately deplete the bodys supply of helper T cells and lead to the collapse of the hosts defences An untreated HIV infection exhibits distinct phases, in which the loss of helper T cells happens at different rates and appears to be driven by different mechanisms In the acute or initial, phase, HIV virions enter the hosts body and begin to replicate HIV gains entry into a host cell by first latching onto the cell-surface protein CD4, then binding
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