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Introduction

Human immunodeficiency virus attacks the immune system by destroying CD4+ T cells, white blood cells that protect the body from infection. During HIV’s initial attack, it attaches to CD4 receptor cells injecting its’ RNA genetic material. The enzyme reverse transcriptase converts its’ RNA into DNA allowing HIV to use the CD4 cell’s machinery to replicate itself and travel through the body.As the virus attacks these cells, the immune system becomes weaker causing the body to be unable to fight off infection, leading to the development of AIDS. Although HIV can be treated through the use of antiretroviral therapy there is currently no cure (“The HIV Life Cycle, 2015).HIV’s vast genetic variability makes treatment difficult.This variability is due to the high mutation and recombination rates of the reverse transcriptase enzyme causing HIV viral sequences to differ by up to 10% in each individual (Hemelaar, 2012). An estimated 36.9 million people were suffering from HIV around the world in 2014 (“Global HIV and AIDS Statistics,” 2015).

The Origin of HIV

There are two types of HIV known, HIV-1 and HIV-2 with HIV-1 being by far the most common and most infectious of the two strains. Research has shown that HIV-1 is closely related to the SIV virus (simian immunodeficiency virus) that attacks the immune system of chimpanzees and HIV-2 is closely related to a strain of SIV that infects sooty mangabeys. Chimpanzees became infected with 2 different strains of SIV after eating two smaller species of monkeys (red-capped mangabeys and spot-nosed monkeys). These two strains joined together forming a third strain known as SIVcpz that could be passed on to other chimpanzees as well as to humans. It is believed that this virus was transmitted into humans as a result of them consuming chimpanzee meat or being exposed to their blood. Once inside its new host the virus adapted into what we know as HIV-1. Each time the virus was transferred from chimpanzee to human it developed slightly differently leading to the four strains of HIV-1 (M,N,O, and P). HIV-2 was transferred from sooty mangabeys to humans in a similar way. It is far less infectious and is mainly found among people in a few West African countries (Mali, Mauritania, Nigeria, and Sierra Leone)(“Origin of HIV & AIDS,” 2015) . The first known case of HIV-1 was detected in a man from Kinshasa of the Democratic Republic of the Congo during the 1950’s (“Where Did HIV Come From,” 2011).This area is known to have the most genetic diversity among HIV strains, indicating that there were several different instances of SIV being transferred to humans. People first became aware of HIV and AIDS when it began emerging in the United States and it wasn’t until this time that it became recognized as a medical condition. (“Origin of HIV & AIDS,” 2015).

Life Cycle

During early infection, HIV is macrophage tropic, meaning that it only infects natural killer cells, CD8+ killer T cells, macrophages, cells of the nervous system, and dendritic cells. During that phase, the cells harbor, replicate, and bud HIV without lysis. On the contrary, during later infections, HIV is T-lymphocyte tropic, meaning it infects CD4+ T lymphocytes and will lyse them during production of new viruses, making it a productive infection. HIV enters a cell by interacting its gp120 portion, the head portion of the protruding glycoprotein, with CD4, the major cellular receptor that is abundantly present on T lymphocytes. This interaction causes a conformational change in gp120 and gp41, the spike portion of the protruding glycoprotein, resulting in the exposure of new binding regions on these proteins, thus causing a co-receptor reaction with either CCR5, the macrophages’ co-receptor, or fusin, the T lymphocyte co-receptor. The virus then embeds into the membrane of the CD4+ cell. The gp41 protein changes into a coiled shape that brings the virus and cell membrane close to each other, allowing the fusion of the virus’ membrane and the host cell, resulting in entry and uncoating, which is the release of viral nucleic acids. In the cytoplasm, the viral RNA is converted to DNA by the HIV-encoded reverse transcriptase. The reverse transcriptase binds to the tRNAlys, which is bound to the RNA genome that serves as a primer for the reverse transcriptase, initiating DNA synthesis. When the reverse transcription is completed, it produces a double-stranded DNA (dsDNA) that contains long terminal repeats (LTRs) located at the end of the viral genome. The viral DNA is transported to the nucleus where it may be integrated into the host’s chromosomal DNA, which is catalyzed by integrase protein found on the HIV.

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