HIV Immune System Invasion
Viruses are a single or double strand of DNA or RNA surrounded by a protein membrane (resembling the organic) but because they cannot survive or reproduce without infecting a host cell, they are not considered living things. A retrovirus is a parasite-like virus that infiltrates the nucleus of a host cell and uses its own RNA to produce DNA which the host cell mistakes for its own DNA and begins making copies, effectively making copies of the virus. A lentivirus is a retrovirus with a long incubation period, which is the period of time after the virus has infiltrated the host cell and for which there are no signs or symptoms in the host body of any disease or disorder. The specific type of lentivirus we will discuss in this article is the human immunodeficiency virus (HIV), which eventually causes acquired immunodeficiency syndrome (AIDS), the disease that is responsible for progressively worsening failures of the human immune system, rendering the body helpless to fight a wide variety of opportunistic pathogens. Before we begin discussion, it should be noted that while there have been some isolated incidents of people recovering from AIDS, no cure has yet to be found and in most cases, it is simply a death sentence.
The HIV Infection and Invasion
People can be infected with HIV by a transfer of bodily fluids (blood, breast milk, semen, vaginal fluids, etc.) Once inside, HIV targets key cells of the immune system in order to cause a deficiency in its function, as the virus’ name suggests, and it accomplishes this by way of its deceptive docking glycoprotein that connects to the target cell’s compatible receptors, giving the cell no reason to raise any alarms. Typically, HIV has a long incubation period, which means that it could have infected the target cells and began multiplying for a long time without the host body noticing in terms of symptoms, and this period for HIV can be as little as 1 year and last up to 10 years. After the incubation period, HIV becomes active – rather than just being copied along with the DNA of the target cells, HIV leaves the target cell, often destroying it, to infect more cells, rapidly spreading throughout the body and eventually rendering the immune system helpless against countless types of invasions that the body could normally easily fend off, the disorder known as AIDS.
HIV’s Main Targets
There are five main types of white blood cells: lymphocytes, neutrophils, monocytes, basophils, and eosinophils, where neutrophils and monocytes are phagocytic (cellular debris eaters) and lymphocytes are the main type of immune response cells, including B cells, T cells, and NK cells, some of which can eventually differentiate into the antibody-producing plasma cells. The monocytes can develop into phagocytic macrophages or a very special type called dendritic cells, so named because they have projections resembling the dendrites of nerve cells. There are four main categories of T-cells: Helper, Killer, Suppressor, and Memory. CD4+ is a type of helper T-cell, so named because of the type of glycoprotein receptor existing on its surface. HIV targets CD4+ cells because of their ability to recognize antigens and consequently stimulate B-cells that develop into antibody-producing plasma cells and killer T-cells that destroy pathogens. The virus attacks macrophages because these destroy malevolent intruders by ingesting them. And it targets dendritic cells in the types of tissue that are exposed to the external environment (like the skin, nose, lungs, stomach, and intestines) because even though dendritic cells are blood cells, they have the ability to sense antigen material and alert T-cells to initiate the immune response, acting as messengers between the invading pathogen and the T-cells.
The Figures above do a nice job showing how HIV infiltrates the various target cells of the immune system. HIV’s docking glycoprotein is received by the receptors in the plasma membranes of the target cells. For macrophages and helper T-cells, these are CD4 glycoproteins coupled with CXCR4 and CCR-5 co-receptors, where CXCR4 are found in helper T-cells and CCR-5 are found in macrophages. From both figures 2 and 3, we can see the difference between the workings of a latent HIV infection (during the incubation period) and an active one, where the HIV breaks out of the target cell to spread throughout the body and infect more cells. A dendritic cell hosts HIV by way of a DC-SIGN lectin receptor that can either guide the virus to a CD4+ by “surfing” the perimeter of the dendritic cell until such time that it comes in close proximity to a CD4+ helper T-cell, which is inevitable because dendritic cells serve as messengers that sense invasions from the external environments and then communicate this with helper T-cells in order to initiate the immune response, or the DC-SIGN lectin receptor can trigger endocytosis into the dendritic cell in order to guide the HIV out of the cell and into the CD4+ cell, with the help of vesicles. Dendritic cells also have the CD4 glycoprotein receptor and the aforementioned co-receptors and HIV can penetrate and break out from them like they do with macrophages and CD4+ cells. In spite of the differences in how HIV enters the target cell, its end goal is the same – infiltrate, replicate, possibly destroy, and spread. The most important and most well-documented invasions of any of its target cells is that of its invasion of the helper T-cell and this is what we discuss in detail next.
The Human Immunodeficiency Virus (HIV) first binds with the CD4 receptors and CCR5 co-receptors of helper T-cells by way of its docking glycoprotein combination of gp41 and gp120, and because the docking glycoproteins bind so naturally with the receptors and co-receptors, the CD4 cell is none the wiser and welcomes it into the cell. The binding induces fusion of the virus’ membrane into the plasma membrane, such that only the RNA, the virus’ genetic material, is released into the cell while the membranes are joined together. The capsid, similar to the nuclear membrane of a living cell, diffuses into the cell while the RNA, reverse transcriptase enzyme, and protease stay in close proximity to one another. Eventually, the process of reverse transcription occurs, whereby a single-strand of RNA is converted into double strands of DNA by the reverse transcriptase enzyme. This HIV DNA then makes its way into the nucleus and with the help of the protease, cuts the helper T-cell’s DNA and fits itself into the longer DNA double strands and becomes a part of the T-cell’s DNA. This is the stage of its invasion where it can lie in wait, the incubation period, and multiply along with the cell. RNA version copies are made from this new infected DNA. These copies can be converted into HIV protein chains or they can simply float out towards the plasma membrane of the CD4 cell, accompanied by the protease and reverse transcriptase enzymes. The protein chains that were formed are cut by the protease and used in the formation of the HIV membrane and the capsid. The HIV RNA strands, protease, and reverse transcriptase enzymes are all bottled in the capsid, once it forms, and the rest of the HIV is assembled by the HIV proteins and the CD4 cell membrane in a reverse-fusion fashion. The newly formed HIV particle departs the helper T-cell, having damaged the CD4 cell’s plasma membrane, and travels to infect other cells, so that the virus can spread.
HIV is a very curious virus. It can be contracted through bodily fluids and once it makes its way inside, it targets the ideal cells – the CD4+ helper T-cell, the dendritic cell, and the macrophage – for crippling the human immune system. From its docking glycoproteins to the package in its nucleus-like capsid, HIV seems like the perfect package for infiltrating an enemy, custom tailored for the human immune system. It penetrates its target cell through the binding of its docking glycoproteins with the receptors and co-receptors of the target cell, fuses with the plasma membrane, empties its contents into the cell, which then is converted to form HIV DNA, establishing its control center from which it will multiply and invade other cells, spreading rapidly. Once the invasion is complete, the immune system is essentially disabled and the body left prone to any and all disorders, the condition known as AIDS. The uniqueness of HIV in its ability to infiltrate the human immune system, disguise itself as a non-pathogen, incorporate itself into the fabric of the target cell, lie in wait, multiplying with the cell, and then spread rapidly, destroying these key components of the human immune system, this uniqueness, it is what makes it incurable, to this very day.