User:Amatorio.1/sandbox

Research Question: HIV is a virus that causes AIDS, which is a life-threatening disease that degrades the immune system leading to life-threating conditions. What are the origins of the HIV virus? How did the SIV virus make the evolutionary leap from its simian hosts to human ones?

Sources:

1.	Heuverswyn, Fran, and Martine Peeters. "The Origins of HIV and Implications for the Global Epidemic." Current Infectious Disease Reports: 338-46. Web. 14 Sept. 2014.

a.	This paper discusses if other primate viruses are responsible for the spread and the emergence of the HIV virus. They are looking at other primate lentiviruses to see if they too were transferred from the simian host to a human one. They look at the different strains of HIV (1 and 2) and compare their theoretical origins. 2.	Sharp, P. M., E. Bailes, R. R. Chaudhuri, C. M. Rodenburg, M. O. Santiago, and B. H. Hahn. "The Origins of Acquired Immune Deficiency Syndrome Viruses: Where and When?" Philosophical Transactions of the Royal Society B: Biological Sciences (2001): 867-76. Web. 14 Sept. 2014.

a.	This article talks about the inferred geographical origin of the HIV-1 virus and how the cross-species transmission was not the cause of the polio vaccine, but was from the contamination of bush meat consumption in Western Africa. The HIV-1 virus is known to be genetically similar to a virus that affects chimpanzees while the HIV-2 virus has been found to be similar to another type of monkey which is native to the area that is known to be endemic to the HIV-2 virus.

3.	Heeney, J. L. "Origins of HIV and the Evolution of Resistance to AIDS." Science: 462-66. Web. 14 Sept. 2014.

a.	This article explains how HIV adapts through positive selection, mutation, and recombination. Other studies have found non-human primates infected with an HIV-like virus but are resistant to AIDS. Using this information, the authors are trying to find information that may be relevant to the prevention of the spread of HIV/AIDS.

4.	Jones, Leandro R., Darío A. Dilernia, Julieta M. Manrique, Franco Moretti, Horacio Salomón, and Manuel Gomez-Carrillo. "In-Depth Analysis of the Origins of HIV Type 1 Subtype C in South America." AIDS Research and Human Retroviruses: 951-59. Web. 14 Sept. 2014.

a.	This paper discusses how there maybe other areas in the world where the HIV-1 virus may have originated. Evidence from phylogenetic ancestry, and the shortage of epidemiological data leads to Argentina as another possible place for where the disease may have originated.

5.	Rambaut, Andrew, David Posada, Keith A. Crandall, and Edward C. Holmes. "The Causes And Consequences Of HIV Evolution." Nature Reviews Genetics: 52-61. Web. 14 Sept. 2014.

a.	This paper discusses the causes of the HIV virus and how its genetic recombination can cause deadly consequences that prevent the progress for the treatment of this virus. Extensive sampling of the HIV genetic material may be the key to developing a successful vaccine. This paper will also try and alleviate the time in which HIV was transmitted from simians to humans.

10/1 Assignment:

Sentence Added: A study published in 2014 also discussed that bushmeat in other parts of the world, such as Argentina, maybe a possible location for where the disease originated. link: https://en.wikipedia.org/wiki/History_of_HIV/AIDS

Source: Jones, Leandro R., Darío A. Dilernia, Julieta M. Manrique, Franco Moretti, Horacio Salomón, and Manuel Gomez-Carrillo. "In-Depth Analysis of the Origins of HIV Type 1 Subtype C in South America." AIDS Research and Human Retroviruses: 951-59. Web. 14 Sept. 2014.

Corrections/Suggestions: Amatorio.1, EEOB 3310 Suggestions

1. According to some research papers, there maybe other simian viruses that are the cause of the emergence of the HIV virus. They indicated that some simian viruses are closely linked to HIV virus.

2. The addition of "current research" section maybe beneficial to this article because it's title is "History of HIV/AIDS". There are several research organizations that may have some insight in this.

3. One of the sections "Origin and epidemic emergence" has no citations in it. Maybe adding some citations will help the credibility of that part of the article.

The Origins of HIV/AIDS
AIDS, or acquired immunodeficiency syndrome, is a chronic and deadly illness that debilitates the immune system that leaves the body defenseless against other pathogens. A virus called Human Immunodeficiency Virus (HIV) that lies in the bodily fluids of an infected individual causes AIDS. There are two different types of HIV, HIV-1 and HIV-2. HIV-2 is seen at higher concentration in Western Africa and is less likely to be transmitted than the predominant HIV-1 (“HIV Strains: Types, Groups, and Subtypes” 2004). HIV-1, therefore, is the most common strain of the virus. HIV spreads from organism to organism through infected blood, pregnancy (from mother to infant), or bodily fluids (usually from unprotected sexual contact) (Mayo Clinic Staff 2014). The HIV virus infects host cells through the CD4 receptor and then releases its genetic material into the cell. The genetic material then integrates itself into the DNA of the host cell. The altered DNA gets replicated and activated through transcription and translation using many different enzymes. After the replication and activation process is complete, new virus capsules are made in the cell and then burst out of the host cell to infect more cells (“HIV lifecycle” 2009). The virus stays dormant for many years and slowly destroys the immune system and once the immune system is compromised, through a significant reduction of t-cells, the disease progresses to AIDS. The first reported case of AIDS in the United States was in 1981 and two years later, the first HIV virus was isolated (Rambaut et al. 2004). Currently, there are 33.4 million people living with HIV/AIDS, and more than 25 million have died from the disease since 1981 (“Global Statistics” 2009). Approximately 97% of the cases are reported to be in low and middle-income countries (particularly in the Sub-Saharan area) and densely populated areas in Asia (“Global Statistics” 2009). In the United States, African Americans are known to have higher cases of HIV/AIDS along with the gay community. Conspirators believe that the HIV virus was synthesized by the government and was made to “kill” the minority populations (blacks, Latinos, gays, etc.) (Bohnert, et al. 2009). According to a survey study done by Bohnert, et al., and not many Americans believe this theory. There are a few, but strongly supported, theories that explain the emergence of the HIV virus in humans. The first of which is the zoonotic transfer of the Simian Immunodeficiency Virus (SIV) from simians (particularly chimpanzees, mangabeys, and macaques) to humans. A second theory lies with the non-human primates of South America (Jones, et al. 2009). This analysis will focus primarily on the emergence of the most common strain of HIV, which is HIV-1.

Theories of Origin: SIV
The most commonly accepted theory for the emergence of the HIV virus is the zoonotic transmission from simian and human host. An analysis done by Chitnis, et al., stated that HIV originated from three different SIV zoonotic transmissions from non-human primates in equatorial Africa (Chitnis, et al. 2000). Through eating underprepared and un-sanitized bushmeat (specifically primates), the hunters in the jungles of the Sub-Sahara region fostered an opportunity for SIV to make the evolutionary leap towards human hosts (Chitnis, et al. 2000). Bushmeat consumption was a direct effect of the French occupation of Africa. Prior to WWII, native Africans were forced out of the rural areas because of the French demand for resources. Since rural Africans were not keen to agricultural practices in the jungle, they turned to non-domesticated meat as their primary source of protein. This over exposure to bushmeat and malpractice of butchery increased blood-to-blood contact, which then increased the probability of transmission. Once the initial exposure was successful, the risqué behavior of individuals (such as prostitution, rape, etc.) led to a dramatic growth of transmission between human hosts (Chitnis, et al. 2000). The first SIV virus, SIVmac, was discovered in 1983 at the New England Regional Primate Research Center (Van Heuverswyn, et al. 2007). Other research facilities, around the same time, have found similar symptoms in different kinds of wild primates that were from equatorial Africa. Most of the cases had the same pattern in which healthy apes came into contact with ones that carried the virus (Van Heuverswyn, et al. 2007). SIVmac, which projected an AIDS-like illness in a macaque, was analyzed genetically and found to be closely related to the other strains of SIV found in other primates. (Van Heuverswyn, et al. 2007). This proposed a possibility of a simian origin to HIV-1. The next SIV strain that was isolated was from chimpanzees (SIVcpz). Independent data has suggested that constant recombination of SIVcpz has given rise to new strains (Heeney, et al. 2006). The different sub-strains of the SIVcpz family contained a gene called vpu, which was also present in HIV-1 of the M and N subtype. (Van Heuverswyn, et al. 2007). The third subtype, HIV-1 O, had been analyzed and found to be closely related to SIVgor, a strain that originates from gorillas (Heeney, et al. 2006). The SIVcpz family was sorted through and analyzed until a strain of SIVcpz, called SIVcpzPTT was considered to be the missing evolutionary link between SIV and HIV-1 (types M and N) (Van Heuverswyn, et al. 2007). At this point, it is not clear whether or not gorillas were the primary source of HIV-1 O. There is a slight possibility that the SIVcpz strain from chimpanzees gave rise to the SIVgor in tandem with HIV-1 O (Sharp, et al. 2001). Modern genetic analysis, however, favors the theory that chimpanzees were the original and immediate source of HIV-1, which is strictly found in humans. (Sharp, et al 2010). However, further research was hindered due to the primates being critically endangered. Sample analyses resulted in little data due to the rarity of experimental material. The researchers, however, were able to hypothesize a phylogeny from the gathered data. They were also able to use the molecular clock of a specific strain of HIV to determine the initial date of transmission, which is predicted to be around 1915-1930 (Sharp, et al 2001). A similar theory pinned the origin of the HIV virus to be in South America. HIV-1C, a subtype of HIV, was theorized to have its origins circulating among South America (Jones et. al 2009). The consumption of bushmeat is also the most probable cause for the emergence of HIV-1C in South America. However, the types of apes, shown to carry the SIV virus, are different in South America. The primary point of entry, according to researchers, is somewhere in the jungles of Argentina or Brazil (Jones et. al 2009). An SIV strain, closely related to HIV, was interspersed within a certain clade of primates. This suggests that the zoonotic transmission of the virus may have happened in this area (Jones et. al 2009). Continual emigration between countries escaladed the transmission of the virus. Other scientists believe that the HIV-1C strain circulated in South America at around the same time that the HIV-1C strain was introduced in Africa (Jones et. al 2009). Very little research has been done on this theory because it is fairly young. However, promising evidence indicates that there may be some validity to this hypothesis. Finding the correct geographical origin of HIV can foster future research in that area to better understand its close evolutionary ties.

Conclusion and Significance
HIV’s ability of recombination within the host hinders the ability of the researchers to understand its true origins and compromises the ability to develop anti-retroviral drugs. HIV’s ability to fix mutations allows it to invade host cells successfully because the immune response is challenged constantly (Rambaut et al. 2004). With the help of the fixed mutation ability, HIV gene selection has shown to be positive for the virus meaning that the mutations that arise within HIV tend to be beneficial to it (Rambaut et al. 2004). A second characteristic of HIV is its evolution within/among its host. Evolution within the host, as stated above, remains positive. Its evolution among the host shows very little correlation with the viruses’ fitness (Rambaut et al. 2004). Since there is low genetic diversity among HIV viruses, natural selection has little to no effect on the virus. The bottleneck-like effect of the HIV’s genes essentially homogenizes the entire population (Rambaut et al. 2004). With all these to consider, drug resistance among HIV virus remains as a huge problem. With exposure to certain drugs, HIV may develop a resistance that is then passed on quickly because of its high reproductive rate (Rambaut et al. 2004). HIV’s malleable characteristics allow it to successfully evade a generalized treatment. By researching HIV’s origin, scientists are able to find the genes of drug resistance and use it to predict future treatments that would be effective. This virus affects millions of people and its growth is set to increase at faster and faster rates. If research is slowed down, even by a few years, this virus will already have evolved traits that will make it more aggressive and/or resistant to current treatments. Essentially, both the interactions of humans with nature and the inherit ability of the virus worked together to create a virus that is successful in its ability reproduce and to use its environment to ensure survivability. Human overexposure to SIV may have effectively stressed the virus to rapidly evolve and ensure its success within the non-human primates. HIV happened to be an SIV virus that was exposed to a human host and by chance, thrived. Its true geographical origin is still under debate to this day and even the most commonly accepted theory, which is bushmeat consumption, is being challenged.

Introduction
AIDS, or acquired immunodeficiency syndrome, is a chronic and deadly illness that debilitates the immune system that leaves the body defenseless against other pathogens. A virus called Human Immunodeficiency Virus (HIV) that lies in the bodily fluids of an infected individual causes AIDS. There are two different types of HIV, HIV-1 and HIV-2. HIV-2 is seen at higher concentration in Western Africa and is less likely to be transmitted than the predominant HIV-1 (“HIV Strains: Types, Groups, and Subtypes” 2004). HIV-1, therefore, is the most common strain of the virus. HIV spreads from organism to organism through infected blood, pregnancy (from mother to infant), or bodily fluids (usually from unprotected sexual contact) (Mayo Clinic Staff 2014). The HIV virus infects host cells through the CD4 receptor and then releases its genetic material into the cell. The genetic material then integrates itself into the DNA of the host cell. The altered DNA gets replicated and activated through transcription and translation using many different enzymes. After the replication and activation process is complete, new virus capsules are made in the cell and then burst out of the host cell to infect more cells (“HIV lifecycle” 2009). The virus stays dormant for many years and slowly destroys the immune system and once the immune system is compromised, through a significant reduction of t-cells, the disease progresses to AIDS. The first reported case of AIDS in the United States was in 1981 and two years later, the first HIV virus was isolated (Rambaut et al. 2004). Currently, there are 33.4 million people living with HIV/AIDS, and more than 25 million have died from the disease since 1981 (“Global Statistics” 2009). Approximately 97% of the cases are reported to be in low and middle-income countries (particularly in the Sub-Saharan area) and densely populated areas in Asia (“Global Statistics” 2009). In the United States, African Americans are known to have higher cases of HIV/AIDS along with the gay community. Conspirators believe that the HIV virus was synthesized by the government and was made to “kill” the minority populations (blacks, Latinos, gays, etc.) (Bohnert, et al. 2009). According to a survey study done by Bohnert, et al., and not many Americans believe this theory. There are a few, but strongly supported, theories that explain the emergence of the HIV virus in humans. The first of which is the zoonotic transfer of the Simian Immunodeficiency Virus (SIV) from simians (particularly chimpanzees, mangabeys, and macaques) to humans. A second theory lies with the non-human primates of South America (Jones, et al. 2009). This analysis will focus primarily on the emergence of the most common strain of HIV, which is HIV-1.

Theories of Origin: SIV
The most commonly accepted theory for the emergence of the HIV virus is the zoonotic transmission from simian and human host. An analysis done by Chitnis, et al., stated that HIV originated from three different SIV zoonotic transmissions from non-human primates in equatorial Africa (Chitnis, et al. 2000). Through eating underprepared and un-sanitized bushmeat (specifically primates), the hunters in the jungles of the Sub-Sahara region fostered an opportunity for SIV to make the evolutionary leap towards human hosts (Chitnis, et al. 2000). Bushmeat consumption was a direct effect of the French occupation of Africa. Prior to WWII, native Africans were forced out of the rural areas because of the French demand for resources. Since rural Africans were not keen to agricultural practices in the jungle, they turned to non-domesticated meat as their primary source of protein. This over exposure to bushmeat and malpractice of butchery increased blood-to-blood contact, which then increased the probability of transmission. Once the initial exposure was successful, the risqué behavior of individuals (such as prostitution, rape, etc.) led to a dramatic growth of transmission between human hosts (Chitnis, et al. 2000). The first SIV virus, SIVmac, was discovered in 1983 at the New England Regional Primate Research Center (Van Heuverswyn, et al. 2007). Other research facilities, around the same time, have found similar symptoms in different kinds of wild primates that were from equatorial Africa. Most of the cases had the same pattern in which healthy apes came into contact with ones that carried the virus (Van Heuverswyn, et al. 2007). SIVmac, which projected an AIDS-like illness in a macaque, was analyzed genetically and found to be closely related to the other strains of SIV found in other primates. (Van Heuverswyn, et al. 2007). This proposed a possibility of a simian origin to HIV-1. The next SIV strain that was isolated was from chimpanzees (SIVcpz). Independent data has suggested that constant recombination of SIVcpz has given rise to new strains (Heeney, et al. 2006). The different sub-strains of the SIVcpz family contained a gene called vpu, which was also present in HIV-1 of the M and N subtype. (Van Heuverswyn, et al. 2007). The third subtype, HIV-1 O, had been analyzed and found to be closely related to SIVgor, a strain that originates from gorillas (Heeney, et al. 2006). The SIVcpz family was sorted through and analyzed until a strain of SIVcpz, called SIVcpzPTT was considered to be the missing evolutionary link between SIV and HIV-1 (types M and N) (Van Heuverswyn, et al. 2007). At this point, it is not clear whether or not gorillas were the primary source of HIV-1 O. There is a slight possibility that the SIVcpz strain from chimpanzees gave rise to the SIVgor in tandem with HIV-1 O (Sharp, et al. 2001). Modern genetic analysis, however, favors the theory that chimpanzees were the original and immediate source of HIV-1, which is strictly found in humans. (Sharp, et al 2010). However, further research was hindered due to the primates being critically endangered. Sample analyses resulted in little data due to the rarity of experimental material. The researchers, however, were able to hypothesize a phylogeny from the gathered data. They were also able to use the molecular clock of a specific strain of HIV to determine the initial date of transmission, which is predicted to be around 1915-1930 (Sharp, et al 2001). A similar theory pinned the origin of the HIV virus to be in South America. HIV-1C, a subtype of HIV, was theorized to have its origins circulating among South America (Jones et. al 2009). The consumption of bushmeat is also the most probable cause for the emergence of HIV-1C in South America. However, the types of apes, shown to carry the SIV virus, are different in South America. The primary point of entry, according to researchers, is somewhere in the jungles of Argentina or Brazil (Jones et. al 2009). An SIV strain, closely related to HIV, was interspersed within a certain clade of primates. This suggests that the zoonotic transmission of the virus may have happened in this area (Jones et. al 2009). Continual emigration between countries escaladed the transmission of the virus. Other scientists believe that the HIV-1C strain circulated in South America at around the same time that the HIV-1C strain was introduced in Africa (Jones et. al 2009). Very little research has been done on this theory because it is fairly young. However, promising evidence indicates that there may be some validity to this hypothesis. Finding the correct geographical origin of HIV can foster future research in that area to better understand its close evolutionary ties.

Conclusion and Significance
HIV’s ability of recombination within the host hinders the ability of the researchers to understand its true origins and compromises the ability to develop anti-retroviral drugs. HIV’s ability to fix mutations allows it to invade host cells successfully because the immune response is challenged constantly (Rambaut et al. 2004). With the help of the fixed mutation ability, HIV gene selection has shown to be positive for the virus meaning that the mutations that arise within HIV tend to be beneficial to it (Rambaut et al. 2004). A second characteristic of HIV is its evolution within/among its host. Evolution within the host, as stated above, remains positive. Its evolution among the host shows very little correlation with the viruses’ fitness (Rambaut et al. 2004). Since there is low genetic diversity among HIV viruses, natural selection has little to no effect on the virus. The bottleneck-like effect of the HIV’s genes essentially homogenizes the entire population (Rambaut et al. 2004). With all these to consider, drug resistance among HIV virus remains as a huge problem. With exposure to certain drugs, HIV may develop a resistance that is then passed on quickly because of its high reproductive rate (Rambaut et al. 2004). HIV’s malleable characteristics allow it to successfully evade a generalized treatment. The current treatment for HIV/AIDS is a cocktail of antiretroviral drugs. There are approximately 20 different antiretrovirals approved by the US Food and Drug Administration that targets the reverse transcriptase or protease of the virus (Simon, et al. 2006). By alternating the different medicines, the HIV virus’ ability to replicate is suppressed significantly. In fact, the virus’ replication ability is suppressed so much that it delays the emergence of HIV-resistant traits to flourish. This form of treatment is inaccessible to most of HIV population, however. Current estimates suggest that almost 80% of people infected by HIV-1 do not have access to any kind of retroviral (Simon, et al. 2006). And even with access, the HIV virus has developed a resistance to the most commonly distributed drug (Simon, et al. 2006). By researching HIV’s origin, scientists are able to find the genes of drug resistance and use it to predict future treatments that would be effective. This virus affects millions of people and its growth is set to increase at faster and faster rates. If research is slowed down, even by a few years, this virus will already have evolved traits that will make it more aggressive and/or resistant to current treatments. Essentially, both the interactions of humans with nature and the inherit ability of the virus worked together to create a virus that is successful in its ability reproduce and to use its environment to ensure survivability. Human overexposure to SIV may have effectively stressed the virus to rapidly evolve and ensure its success within the non-human primates. HIV happened to be an SIV virus that was exposed to a human host and by chance, thrived. Its true geographical origin is still under debate to this day and even the most commonly accepted theory, which is bushmeat consumption, is being challenged.

Additions/Edits to Article
Link: https://en.wikipedia.org/wiki/History_of_HIV/AIDS

The sources are cited in the wikipedia format on the article.

Prior to WWII, some Sub-Saharan Africans were forced out of the rural areas because of the European demand for resources. Since rural Africans were not keen to agricultural practices in the jungle, they turned to non-domesticated meat as their primary source of protein. This over exposure to bushmeat and malpractice of butchery increased blood-to-blood contact, which then increased the probability of transmission.

However, phylogenetic and DNA research has found that the strain HIV-1 group O is more closely related to SIVgor.

HIV-1C, a subtype of HIV was theorized to have its origins circulating among South America. The consumption of bushmeat is also the most probable cause for the emergence of HIV-1C in South America. However, the types of apes, shown to carry the SIV virus, are different in South America. The primary point of entry, according to researchers, is somewhere in the jungles of Argentina or Brazil. An SIV strain, closely related to HIV, was interspersed within a certain clade of primates. This suggests that the zoonotic transmission of the virus may have happened in this area. Continual emigration between countries escaladed the transmission of the virus. Other scientists believe that the HIV-1C strain circulated in South America at around the same time that the HIV-1C strain was introduced in Africa. Very little research has been done on this theory because it is fairly young. However, promising evidence indicates that there may be some validity to this hypothesis.

Further research was hindered due to the primates being critically endangered. Sample analyses resulted in little data due to the rarity of experimental material. The researchers, however, were able to hypothesize a phylogeny from the gathered data. They were also able to use the molecular clock of a specific strain of HIV to determine the initial date of transmission, which is predicted to be around 1915-1930.