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Human immunodeficiency syndrome (HIV) is known worldwide for its deadly effect on many countries especially Africa. In this document, a review of articles and journals reveals four theories (genocidal or conspiracy belief, natural, oral polio vaccine and iatrogenic theories) examined in other to clearly define the origin of HIV/AIDS. Also the ordered steps of HIV pathogenesis with much emphasis on its effect on the immune system are clearly outlined in this document.
Viruses are infectious agents and contain only one kind of nucleic acid (RNA or DNA) as their genome that is encased in a protein protein shell. The protein shell may also in turn be surrounded by a lipid-containing shell. They usually range from about 20 nm to about 300 nm in diameter. A complete virus particle containing these structural elements is called a virion.2 7 A virion can be envisioned as a delivery system that surrounds a nucleic acid payload and it is designed to protect the genome and enable the virus to bind to host cells. 7 Viruses are inert in the extracellular environment and are only active in living cells. In living cells, they tap the cells replicative machinary in other to replicate. During replication, the viral genome contains information necessary for programming the infected host cell to synthesize virus-specific macromolecules required for the production of viral progeny. This genomic information includes enzymes required for the initial steps in intracellular viral replication process. Examples of such macromolecules include coat proteins that assemble together to produce capsid, surface antigen and matrix protein. The virus infection may have little or no effect on the host cell or may result in cell damage or death based on the type of virus in question. Each virus has a unique pathogenecity based on the type and structure of the virus in question.
Human immunodeficiency virus (HIV) is the virus that causes AIDS. HIV (figure 1) belongs to the genus Lentivirus, family Rotaviridae (rotavirus) and class retrovirus.2 (20)??? Members of rotavirus have RNA as their genetic material and in other to replicate they make a DNA copy of their RNA in the host cell. A unique feature of lentiviruses is the long interval between the initial infection and the onset of the serious symptoms 17. It is believed that HIV originated from a group of simian immunodeficiency viruses (SIV). There are two types of the virus, namely HIV-1 ( groups M and O) and HIV-2 (subtypes A and B). 13 HIV-1 is more common than HIV-2 and is believed to have originated from wild living chimpanzees because of its close relatedness to the simian immunodeficiency virus (SIV). 13 AIDS was first identified in 1981 and HIV-1 was isolated by the end of 1983. Since then the virus has become a worldwide epidemic. HIV results in the decrease in the efficacy of the immune system. It accomplishes this by a change in its genomic sequence whenever it replicates thereby making white blood cells ineffective against it. It therefore gives opportunistic microbes the opportunity to cause fatal infections in an infected person. 2The intent of this paper is to examine the theories surrounding the origin of HIV and also the pathogenicity of HIV infection in relation to fatal opportunistic infections associated with HIV infection.
MATERIALS AND METHOD.
Journals and articles from Philosophical Transactions from the Royal Society, National Institute of Allergy and Infectious Diseases, NLM Gateway and NAID were consulted for the purpose of this paper. Also, books consulted include two microbiology books.
RESULTS AND DISCUSSION.
THEORIES SURROUNDING THE ORIGIN OF HIV.
Conspiracy beliefs about the origin of HIV/AIDS (Genocidal theory about HIV).
Conspiracy beliefs about the origin of HIV include: "HIV/AIDS is a man made virus that the federal government made to kill and wipe out black people", "AIDS is a form of genocide against blacks" and "AIDS was produced in a government laboratory."1 15 These conspiracy beliefs however is not the same around the world. The basis of this belief originates from racism specifically against African Americans and Latinos (1-carigan and Web)??. In a random door-to-door survey of African Americans in Califonia, twenty-seven percent of African Americans were of the view that "HIV/AIDS is a man made virus that the federal government made to kill and wipe out black people". A further twenty three percent of the people under study were unsure 9(1- klonoff). In a random telephone survey of African Americans living in contiguous United States of America, over twenty percent of men and twelve percent of women somewhat or strongly agreed that "AIDS was produced in a government laboratory." Thirty percent of men and twenty-four percent of women also agreed (1 bogart 2005 ???). In another research in 2005, approximately fifty-five percent of Latinos and fifty percent of African Americans reported believing that the government secretly had the HIV vaccine but this can be linked to lay media publications and broadcast. 8
However, these researches stated above were conducted with an English questionnaire and also recorded a refusal rate of almost half the samples collected. Also, English speaking people were either more or over-represented in the sample taken. This therefore brings into mind the question - Was the sample taken during the experiment representative of the entire population? Nevertheless, conspiracy beliefs are not limited to the African American population but also prevalent among Latinos and non-Hispanic white population. However, such beliefs are not present in the Asian population although the Tuskeegee scandal may explain suspicion in groups other than African Americans. 15
Oral Polio Vaccine Theory (OPV).
Louis Pascal, scientist based in New York, in 1987 developed the idea that AIDS originated from the polio vaccine. There are two types of the HIV as indicated earlier in this document. HIV-1 is linked to AIDS in most parts of the world and appears to diverge from a common ancestor from Central Africa a little before 1960. HIV-2 appears to come from a common ancestor from Western Africa.1 8 12 The closest known relative to HIV is SIV found in the monkeys and chimpanzees. 1 However, this correlation is strong between HIV1 and SIV but not between HIV2 and SIV. Pascal noted that the virus, SIV, was transferred to humans through contamination of cultured polio vaccine on monkey kidney. An example of such vaccine is the Koprowski's polio vaccine that was developed in Wister Institute in Philadelphia. The kidney of the monkey serves as a source of SIV. 1 9 An infected monkey does not show signs of the disease. Current laboratories screen the vaccine for contaminants such as SIV, but before 1985 such screening was not done and hence SIV was transferred to man. In man, SIV then developed in the HIV producing the disease AIDS. 9
Pascal again noted that for a virus to infect a different species, the immune system of this new specie must be reduced. In children less than one year old, the immune system is weak and hence depends on their mother's breast milk for antibodies and nutrition. Breastfeeding therefore serves as a source of infection from an infected mother as well as vaccination with contaminated polio vaccine. 1
Scientific literature, like Pascal's finding, however, provide no direct evidence for HIV's natural evolution from monkeys to man but only circumstantial evidence 8 and also there is no concrete evidence that chimpanzee kidney tissues were used to make the vaccine. Furthermore, HIV and SIV cannot be (or can with difficulty) transmitted orally and even if SIV-infected chimps had been used, SIV from their kidney could not have survived through the final stage of vaccine preparation. 10
"NATURALTRANSFER" AND IATROGENIC THEORIES.
The "natural transfer"10 refers to the exchange of animals, specifically the chimpanzee and monkeys, which were killed by hunters and sold in the market for money or goods. Such trade used to happen in some African countries such as Congo and Gabon. The distribution of chimps and monkeys in some countries such as Burundi, Rwanda, Angola and Equitorial Guinea in 1975 is depicted in figure 3 and this distribution is also related to the initial areas where specific strains of HIV first appeared. Hunters who frequently killed chimpanzees and monkeys were exposed to SIV through cuts and bites from these animals and might have gotten infected with the SIV by a horizontal transfer of the virus. 8 10 The SIV in humans then evolved into HIV.3
Iatrogenic theory on the other hand refers to the transfer of the HIV-1 group M to man due to vaccine trials conducted by the medical profession in finding cure to certain diseases. It postulates that "certain batches of an experimental OPV, CHAT, which was fed to a million persons in Central Africa between 1957 and 1960, were produced in the chimpanzee cells that were infected with SIV. "10 The theory further proposes that these vaccine trials were staged in Belgian colonies, currently known as Democratic republic of Congo, Rwanda and Burundi, and hence the trend of HIV/AIDS in these countries in 1980 and 1981 as shown in figure 2. These vaccines also gave room for the rise of different variants of chimpanzee SIV to become seeded in humans, thus giving birth to most of the group M subtypes that are recognized today. The iatrogenic theory and the OPV theory seems to talk about the same mode of transmission to man.
The virus then spread from these areas to other parts of the world through colonization and urbanization which introduced roads connecting people to distant places across the globe. Also adding to the spread of HIV is the advancement in technology which allows people to travel overseas. 3 However, there has not been any step-by-step scenario to explain the specific mechanics of group M natural transfer such as why HIV and AIDS first emerged first where they did and just how the M subtypes came into being. 10
PATHOGENECITY OF HIV.
HIV is made up of a genetic material (RNA), chemicals and a coating. Upon entry into the human body, it first infects white blood cells called T-Lymphocytes. It does this by attaching to specific cell surface proteins on T-Lymphocytes. There are different types of T-Lymphocytes and some of this includes CD4+ and CD8+ cells. Each of these cells has specific cell surface proteins. CD4+ cells, T and B lymphocytes, macrophages, natural killer cells, dendritic cells, hematopoietic stem cells, endothelial cells, microglial cells in the brain and gastrointestinal epithelial cells all have CD4 cell surface receptor. (19) A second co-receptor is required for entry of HIV 1 into the cell. The virus first binds to the CD4 receptor and then to the co-receptor or Chemokine receptors (CCR5 and CXCR4). Chemokine receptors used by HIV for cell entry are found in on lymphocytes, macrophages, thymocytes, neurons and cells in the colon and cervix. HIV exploits the chemokine signaling network shared among immune cells to gain access to downstream cellular components, which in turn serves as an effective tool to break cellular barriers. 16 Mutation in CCR5 gene in certain individuals therefore delays the progression of HIV-1 infection because the virus cannot penetrate host's cell.
After attachment, HIV causes irreversible conformational changes in the viral cell envelop through its interaction with the cell surface membrane proteins. This conformation results in the activation of gp41 fusion peptide and hence fusion of viral envelop with cell membrane of lymphocytes in lymph organs. The next step is the penetration of HIV into the cytoplasm which is also referred to as engulfment which entails endocytosis of the HIV. After engulfment, the viron uncoats in the cytoplasm of the host cell. Uncoating entails the physical separation of the viral nucleic acid from the outer structural component of the virion so that viral replication can occur. The removal of the outermost structural component of the virion makes HIV lose its infectivity within the host's cell. After the release of the viral components into the cytoplasm of the host cell, the free nucleic components of HIV enter the nucleus of the host's cell and begin the synthetic phase of the viral replicative cycle. In the course of viral replication, the RNA component merges with the genetic material of the host cell. 17 This combined genetic material is then transcribed, translated and specific macromolecules are synthesized in the host's cell to give rise to new copies of HIV with the help of protease. 17 These specific macromolecules include proteins that make up the outercoat of HIV, its specific receptor proteins and its capsid polypeptides.
Newly synthesized viral genome and capsid polypeptides assemble together to form a progeny of HIV. Interestingly, each new progeny of HIV contains a genome unique from the parent one. This genome arises from mutative error in genomic sequence during reverse transcription of the original RNA. After assemblage of progeny cell components, the new HIV buds out of the cell. It then attaches to a new cell resulting in a repetition of the entire pathogenetic process in a new cell. This stage of viral pathogenesis is called shedding. Damage to cell is caused by the excessive amount of viral components that accumulate in the cytoplasm. This either leads to cell lyses or cytopathic effects which develops and eventually results in cell death. Other theories surrounding destruction of infected cells during shedding of progeny HIV includes direct cell killing, syncytia formation, apoptosis and innocent bystanders. ( 19) Direct cell killing is associated with destruction of the cell due to a large amount of virus budding off from the cell surface whiles syncytia formation deals with the fusion of nearby uninfected cells through CD4-mediated fusion and this result in the formation of balloon-like giant cells called syncytia. Apoptosis, on the other hand, refers to programmed cell death that occurs due to disruption of cellular regulation by HIV. Also, HIV binds to uninfected cell surface giving them the appearance of an infected cell and marking them for destruction by killer T cells.
Factors such as age or genetic differences among population, the virulence of an individual strain of the virus and co-infection with other microbes may influence the rate and severity of HIV patjhogenicity.(19)
PROGRESSION OF HIV INFECTION TO AIDS.
Acquired immunodeficiency syndrome (AIDS) is the disease condition produced as a result of HIV pathogenesis. This section of the document deals with the conversion of an uncontrolled HIV infection into full blown AIDS. The main objective of this section of the document is to emphasize the fact that AIDS damages the immune system and gives room for opportunistic infections to have their way and eventually causing death. The course of an untreated HIV infection spans about a decade and involves various stages. These stages include primary infection, dissemination of the virus to lymphoid organs, clinical latency, elevated expression, clinical death and death.
Primary infection of HIV refers to initial entry of the virus into the body through all the modes of acquiring the virus, thus unprotected sexual intercourse and body fluid contact with an infected person. Also associated with primary infection is viremia (presence of viruses in the blood). Viremia is detected between the eight and twelfth weeks of infection and it results in the dissemination of the virus to other areas of the body. It should be noted that the initial site of attack of the virus is seeding in the lymph nodes that forms part of the core of the immune system at this early stage of infection, there is a drop in the numbers of circulating CD4 T cells in the body. This is then followed by an immune response within the first one week to three months of primary infection in which there is an increase the number of circulating CD4 T cells. However, the immune response is unable to eradicate the infection completely and hence HIV infected cells still persist in the lymph nodes.
Immediately following the primary infection stage is the period of latency which lasts for an average of ten years. At this stage, HIV infected cells in lymph nodes assume a level of replication of the virus with an estimated ten billion particles being produced and destroyed each day. At this stage the half-life of CD4 T lymphocytes is one point six (1.6) days due to the high productivity of the virus. It is during this stage that there is a daily mutative error of every nucleotide of HIV genome produced. This action make HIV resistant to white blood cells produced against the initial infection and drugs against the disease.14 Hence it is observed in the graph (figure 3) below that CD4+ T cell count reduces after the initial infection of HIV. This reduction is coupled with the gradual rise in progeny HIV in the body.
Following the latency phase of disease progression is the development of symptoms associated with acquired immune deficiency syndrome (AIDS) if infection is not controlled initially. At this stage, white blood cells are practically ineffective against HIV as dipicted in figure 3 with a drop in CD4+T cells. At this stage, there is an irreversible damage to cells of the immune system with high levels of the virus in the plasma and for HIV1 infections a shift from monocyte-tropic or macrophage-tropic (M-tropic) strains to lymphocyte-tropic (T-tropic) variants. Also HIV disseminate to brain resulting in neurotropic and neuropsychiatric abnormalities associated with AIDS due to the expression of T4 gene in brain cells and other epithelial cells in the body. 5 11 The final stage of HIV infection occurs when a significant number of CD4 lymphocytes have been destroyed and the production of new ones cannot replace the ones destroyed. 17 Fatigue, long-lasting fever and weight loss sets in and are very common signs that an infected HIV/AIDS patient exhibit. Irreversible damage to the immune system, at this stage, due to destruction of HIV-infected CD4 T cells leads to a less efficient immune system. 17 This event gives room for other microorganisms, such as Mycobacterium avium complex and Pneumocystiis carinii pneumonia, that cause diseases and it is these opportunistic diseases that make AIDS deadly.(19)
Genocidal theory, oral polio vaccine theory, natural theory and iatrogenic theory all attempt to explain the etiology of HIV but these theories are not able to clearly state with convincing evidence the exact origin of HIV. Theories such as the oral polio vaccine, natural and iatrogenic theories do not clearly establish the direct link, in terms of evolution or transformation of SIV into HIV but rather base their inferences on belief. Conspiracy (genocidal) theory on the other hand is just to create tension and disbelief between certain population group (the black community) and their government.
AIDS like any other condition would not be deadly if not for its direct and initial effect on the immune system. Current research into HIV/AIDS looks more controlling the pathogenesis of the virus through the use of antiretroviral drugs which does not destroy the virus but rather delays it progression into AIDS. AIDS on the other hand is categorized as a chronic condition which can hasten death if not controlled.