AIDS: Epidemic Of The Decade Essay, Research Paper
INTRODUCTIONThere is no doubt that AIDS is indeed the epidemic of the decade. Not only are there many supporting facts and data, visiting urban cities and third world countries prove this point. Furthermore, AIDS is not only highly infectious, it is also the first major incurable epidemic throughout this biomedical revolution that mankind is going through. This epidemic might actually be the one that will completely wipeout the third world. Scientists, government agencies and pharmaceutical companies are scrambling to find a cure to this epidemic but in the mean time we have to find a way to deal with it, if possible. As we continue into the next millennium with all sorts of problems facing humanity, the choice with regard to AIDS is simple, evolve or die!
INFECTIVITYThe Human Immunodeficiency Virus (HIV) has two different types of strains. HIV-1 is the North American strain while HIV-2 is the African strain. The only real difference between the two is that HIV-2 has the vpx gene while HIV-1 does not. As you can tell by the name, the virus works by gradually deteriorating the immune system. The virus can infect any cell with CD4 molecules on the cell?s membrane. It seems to specifically destroy or disable the CD4+ T cells. These cells are sometimes called “T helper” cells. They work by signalling other cells to perform their special functions. A normal healthy person usually has a CD4+ T cell count of 800 to 1,200 per cubic millimetre of blood. Once a person?s CD4+ T cell count falls below 200/mm3, a person is diagnosed with Acquired Immunodeficiency Syndrome (AIDS). A person diagnosed with AIDS will usually die of an opportunistic infection, not of HIV/AIDS itself.
HIV is a virus and a virus is basically a microscopic bag of protein filled with a strain of DNA or RNA. To be more specific, HIV has a diameter of approximately 1/10,000 of a millimetre and is spherical in shape (see Figure 1-1). The viral envelope consists of two layers of lipid molecules and contains proteins taken from the host cell. There are 72 copies (on average) of a complex HIV protein called Env. Env is made of three or four molecules of a glycoprotein, gp120, that form a cap and a stem consisting of gp41 molecules that anchor the structure to the surface of the viral envelope. HIV belongs to the class of viruses known as retroviruses. HIV is a retrovirus because its viral core is composed of RNA. Inside the viral core there is a capsid that is made of 2000 copies of a viral protein called p24. This capsid surrounds two strands of HIV RNA, each of which contains nine of the virus? genes. Three of these genes (gag, pol, and env) contain information regarding the manufacture of structural proteins and new virus particles. Three regulatory genes (tat, rev, and nef) and three auxiliary genes (vif, vpr and vpu) contain information regarding the production of proteins that allows HIV to infect a cell, produce new copies of the virus or cause disease. At the end of the HIV RNA strands there is a RNA sequence called long terminal repeat (LTR). The LTR acts as a switch to control the production of new viruses. Proteins from the virus or the host cell trigger the LTR. The core of HIV also contains a protein called p7, the nucleocapsid protein and the three enzymes that carry out later steps in the virus’s life cycle: reverse transcriptase, integrase and protease. The p17 protein called the HIV matrix protein, lies between the viral core and the viral envelope.
In order to continue its life in an evolutionary sense, HIV must do what every virus does, and that is, to float around in the blood stream and wait for a cell that it can infect. In HIV’s case it usually waits around until a cell swallows it up with CD4 molecules on its cell membrane. Once it is swallowed the following occurs (see figure 1-2):
Entry and AttachmentThis is when the virus comes in contact with the host cell?s membrane. Once the two membranes meet, the gp120 binds and fuses with the CD4 molecules on the surface of the host cell?s membrane. During this stage the virus will release its HIV RNA, enzymes and proteins into the host cell.
Reverse TranscriptionIn this stage the HIV RNA converts itself into DNA in the cell?s cytoplasm. This process has no correction mechanism so there is often a high rate of error in the transcription. This leads to an especially high mutation rate of HIV.
IntegrationThe new DNA moves to the nucleus of the cell. In the nucleus of the cell the HIV DNA is spliced with the DNA of the cell with the help of HIV integrase. Once the HIV DNA has been incorporated into the cell?s genes it is called a ?provirus”.
TranscriptionFor the provirus to create more viruses it must take over the cell?s protein making machinery. This is done with the messenger RNA (mRNA). mRNA is RNA that can be read by the protein making machinery. Transcription is initiated by the tat gene or by cytokines, which are proteins that are involved with the normal regulation of the immune response. Transcription may also by initiated by molecules such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 which are secreted at higher levels by the cells of HIV infected people. (www.aegis.com)
TranslationThis is the process of the HIV mRNA taking over the cell?s protein making machinery. Once the HIV mRNA is processed in the cell?s nucleus, it is transported to the cytoplasm of the cell. HIV proteins are very important to this process. For example, a protein encoded by the rev gene allows the mRNA that encodes HIV structural proteins to be transported from the nucleus to the cytoplasm. Without this rev protein structural proteins cannot be made. In the cytoplasm, the HIV mRNA takes over the cell’s protein making machinery and begins to produce long chains of viral proteins and enzymes.
Assembly and BuddingNew HIV core proteins, enzymes and RNA gather just inside the cell’s membrane with viral envelope proteins. An immature virus particle then pinches off from the cell membrane taking with it an envelope that includes both cellular and HIV proteins. During this part of the virus’s “life” it is not infectious because the core is not yet mature. The long chains of proteins and enzymes that form the viral core are then cut into smaller pieces by a viral protein called protease. Once the protease has finished its work the virus is ready to infect another cell.
HIV researchers around the world are currently studying how the HIV virus destroys or disables CD4+ T cells. Many of these researchers think that the mechanisms described below happen simultaneously in an HIV infected person. Recent data suggests that billions of CD4+ T cells can be killed almost everyday, eventually overwhelming the body?s ability to reproduce T cells. Here are some of the ways researchers think that HIV kills or disables CD4+ T cells:
Direct Cell KillingInfected CD4+ T cells may be killed directly when large amounts of virus are produced and bud off from the cell surface, disrupting the cell membrane, or when viral proteins and nucleic acids collect inside the cell, interfering with cellular machinery.(www.aegis.com)
Syncytia FormationInfected cells may also fuse with nearby uninfected cells, forming balloon?like giant cells called syncytia. In test?tube experiments at the National Institute of Allergy and Infectious Diseases (NIAID) and elsewhere, these giant cells have been associated with the death of uninfected cells. The presence of so?called syncytia?inducing variants of HIV has been correlated with rapid disease progression in HIV?infected individuals.(www.aegis.com)
ApoptosisSome scientists believe that when an HIV infected cell has its cellular regulation distorted by HIV proteins it undergoes a programmed self-destruct or aptosis. There are reports that indicate HIV infected persons have a much higher rate of aptosis in both their blood stream and in their lymph nodes. Some scientists report that gp120 alone or bound to gp120 antibodies can give false biochemical signal to uninfected cells causing them to commit suicide. (www.aegis.com)
Innocent BystandersUninfected cells may die in an innocent bystander scenario: HIV particles may bind to the cell surface, giving them the appearance of an infected cell and marking them for destruction by killer T cells. Killer T cells may also mistakenly destroy uninfected CD4+ T cells that have consumed HIV particles and that display HIV fragments on their surfaces. Alternatively, because HIV envelope proteins bear some resemblance to certain molecules that may appear on CD4+ T cells, the body’s immune responses may mistakenly damage such cells as well. (www.aegis.com)
AnergyResearchers have shown in cell cultures that CD4+ T cells can be turned off by a signal from HIV that leaves them unable to respond to further immune stimulation. This inactivated state is known as anergy. (www.aegis.com)
SuperantigensOther investigators have proposed that a molecule known as a superantigen, either made by HIV or an unrelated agent, may stimulate massive quantities of CD4+ T cells at once, rendering them highly susceptible to HIV infection and subsequent cell death. (www.aegis.com)
Damage to Precursor CellsStudies suggest that HIV also destroys precursor cells that mature to have special immune functions, as well as the parts of the bone marrow and the thymus needed for the development of such cells. These organs probably lose the ability to regenerate, further compounding the suppression of the immune system. (www.aegis.com)
Researchers have found that it takes about 10 years for the symptoms of AIDS to appear in a HIV infected person. However, it has also been observed that there can be a wide variation in disease progression. Approximately 10 percent of HIV?infected people in these studies have progressed to AIDS within the first two to three years following infection, while 5 to 10 percent of individuals in the studies have stable CD4+ T cell counts and no symptoms even after 12 or more years. Factors such as age or genetic differences among individuals, the level of virulence of an individual strain of virus, and co?infection with other microbes may influence the rate and severity of disease progression. (www.aegis.com)
During the early parts of the HIV infection the virus will infect a large number of T-cells and replicate rapidly. During this phase the virus seeds itself into many different organs of the body, including the lymphatic system, brain, kidneys, skin, and intestines. The person?s blood during this time is very infectious. By the end of this phase, the person?s CD4+ t cell count is decreased by 20 to 40 percent. Scientists don’t know if the T cells are killed or if they “retreat” to the lymphatic organs in preparation for an immune response. Two to four weeks after exposure to the virus, the majority of infected people (70 %) experience flu-like symptoms as the body fights the virus with a massive immune response. During this immune response the body will fight back with killer T cells (CD8 + T cells) and B-cell produced antibodies, which dramatically reduce the HIV levels in the blood stream. A person?s CD4+ T cell count may rebound up to80 or 90 percent of its original.
One reason why HIV is so unique is that for some reason it survives this purge. Some scientists believe that the body?s best soldiers (killer T cells) simply tire themselves out and allow some of the virus to escape and multiply slowly. The killer T cells also stay in the blood stream and ignore the virus stuck in the lymphatic system. More scientists now believe that HIV hides in special parts of the lymphatic system called follicular dendritic cells (FDCs). FDCs are located in the hot spots of the immune activity called germinal centres. FDCs act as a sort of flypaper trapping invading pathogens (including HIV) and hold them until B cells come along to initiate an immune response. Close behind these B cells, CD4+ T cells come to help kill the invaders. When the CD4+ T cells try to help to clean out the FDCs the HIV in the FDCs infects them in large numbers. (AIDS and the Arrows of Pestilence, Charles F. Clark) Over the years even if there is almost no sign of HIV in the blood stream the virus accumulates in the germinal centres. During the time while HIV is accumulating the person may feel no symptoms of HIV from anywhere between two to twelve years. Eventually the virus will kill most of the T cells in the body and a person will get AIDS.
The majority of scientists believe that HIV causes AIDS but there are some scientists that don’t believe this. For example, Peter Duesberg thinks that AIDS is an infectious disease and not a result of HIV. His main point is that HIV is not cytocidal (does not directly kill cells) however HIV is cytocidal because it does directly kill CD4+ T cells, as described above. Duesberg?s second major point is that the body can generate most of the lost T cells. In reality, the virus uses the T cells as hosts so whenever the body reproduces more T cells, the virus has more hosts to infect. Therefore more viruses will be produced and will eventually overwhelm the body?s ability to make more. His third point is that there is no Simian (monkey) model for AIDS. Many however, believe that HIV is a direct “sibling” to SIV (Simian Immunodeficiency Virus). Monkeys die from SIV the same way humans die from HIV. So there is a simian version of AIDS. His final theory is that the drug AZT causes AIDS. This is very hard to believe because AZT works by interrupting the reverse transcription of RNA to DNA, which results in HIV not affecting the immune system.
HIV is very different than any other disease in human history because it specifically attacks the immune system allowing the body to die from an opportunistic infection that is usually too weak to cause death on its own. It is also interesting because it is the first disease that has been discovered during the biomedical revolution that is both highly contagious and has no cure.
TransmissionHIV can be spread in many ways. The main ways that HIV spreads are:
through sexual intercourse with an infected partner
by using recreational drugs intravenously with a syringe that has been used by someone with the virus(http://www.avert.org)
Injecting drug use continues to play an important role in HIV-1 transmission in developed countries, but sexual transmission is responsible for the recent rapid expansion of the epidemic in Asia, India, and the Indian subcontinent. Sexual transmission among homosexual males is still a significant part of epidemic spread in the United States and Europe, but now most experts estimate that homosexual males account for fewer than 50% of new infections in the United States. (Holmberg SD) In the most populous regions of the world, sexual transmission among heterosexuals is the dominant mode of spread.
The other less common modes of transmission of the HIV virus are:
blood transfusions
blood products
mother to baby transmission
infection in the health-care setting
Blood TransfusionsSome people have been infected through a transfusion of infected blood. But in most countries all the blood used for transfusions is now tested for HIV. In these countries where the blood has been tested, infection through a blood transfusion is now extremely rare. (www.aeges.com)
Blood ProductsBlood products, such as those used by people with Hemophilia, are now heat treated to make them safe.
Mother to Baby TransmissionThe virus can be transmitted to the child from the mother before or during the delivery of the newborn. The other mother to child transmission case is through the breast milk that he/she is fed in the early stages of the child’s life.(www.westnet.com)
Infection in the Health-Care SettingSome health-care workers have become infected with HIV by being stuck with needles containing HIV-infected blood. Even fewer have become infected by HIV-infected blood getting into the health-care worker’s bloodstream through an open cut or splashes into a mucous membrane (e.g. eyes or the inside of the nose).
There have only been two documented instances of patients becoming infected by a health-care worker.
Duration of EpidemicThe duration of HIV has been known to stay with the infected individual all of their life because there is no known cure for it. Other illnesses such, as the cold or flu, have been cured over time, because the body is still well enough that the body’s white blood cells can fight it off. However, with HIV, the infected cells attack the white blood cells and destroy them, rendering the body helpless and unable to fight off other illnesses, which would not have affected the body normally. The problem also lies in the fact that HIV, once in the body, does not go for an “all-out attack”. It hides in major reservoirs such as the lymph nodes and stays there; sending out infected cells a little at a time. When the HIV virus has infected enough cells, then the cells attack the body’s defenses and destroy them. Because HIV is a smart virus, it does these accomplishments in astounding ways, which are listed below.
First of all, HIV produces about ten billion copies of itself every day, while the body can only replace about a billion of the white blood cells every day. Second, HIV hides a large percentage of its “army” in reservoirs, and seldom brings them out. Third, a person can have HIV for as long as several years without even knowing they have it, and then HIV suddenly emerges and hits them, killing them in weeks or even days.
There are no cures, but in the future, the human species may adapt to the HIV virus and so it would no longer be an epidemic, but just something that can be cured over time, like the flu or cold.