When I talk with friends about primates and disease, it always surprises me how many are unaware as to how SIV came to be associated with HIV. The long misguided associations of it being a “gay flu,” disease of immigrants and intravenous drug users is long gone, but many stigmatizations remain around the world. Though I suspect many readers are probably well aware of the fact that SIV is the precursor to HIV, this post is to explain how that came about.
Among the many emerging infectious diseases in the last fifty years, few are as intimidating to public health resources as the global Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) epidemic. Since the emergence of HIV/AIDS, the world’s economy, social practices, political relationships, and other aspects of human life have been altered dramatically. Initially seen as the “gay flu,” it was once thought that homosexuals, intravenous drug users, immigrants, and other marginalized groups were the source of the virus. However, recent genetic evidence show the origins of HIV are not linked to these groups. Instead, the origin of HIV/AIDS comes from a very unlikely source, one of which we are all too familiar—our non-human primate ancestors. In our primate kin, a similar virus to HIV evolved over time and allowed them to become the hosts for a disease known as Simian Immunodeficiency Virus (SIV). The analysis of evidence leads scholars to believe HIV is a zoonotic disease transmitted from non-human primates to human primates based on similarities between SIV and HIV on the host identification and location, viral genetic levels, and plausible theories on routes of transmission. Through non-human primates and human interference, SIV became transmissible to humans and developed into HIV.
In order to understand HIV within a proper context, we must first discuss SIV. As it currently stands, thirty-three primate species are known to be the natural hosts of SIV. SIV is a retrovirus, which is a virus that replicates in the host cell via an enzyme known as reverse transcriptase. Through this process, the virus reproduces itself as a part of the host cell’s DNA strands within the cell; thus, making it difficult for the host’s immune system to recognize and ward off further infection. In addition, the virus mutates at an exceptionally high rate to avoid an immune response (Althaus & De Boer 2008). This mutation rate has also led to the shifting of types; types of SIV vary and are recognized depending on the species in which they inhabit. For instance, an infected chimpanzee’s strain would be considered SIVcpz, whereas a sooty manabey’s would be SIVsmm.
This distinction is important to note as it is believed the two types of emergent HIV strains are descended from specific SIV strains; namely, SIVcpz and SIVsmm. Evidence for this is supported in the locations where strains are found. As it turns out, the sooty mangabey is endemic to western Africa; specifically, Sierra Leon to Gabon, which is the area thought to be near where HIV originated. HIV-2, for instance, is believed to originate from SIVsmm and sooty mangabeys. Coincidently, areas in which SIVsmm appears are the exact same as HIV-2 (Gao et al. 1999).
Further support comes from assessing the infectious quality of the SIVsmm strain in human cell cultures. In a polymerase chain reaction study performed by Gao et al. (1992), researchers took mononuclear blood cells from two rural HIV- Liberian agricultural laborers and an HIV+ urban dweller. Then, researchers proceeded to infect the blood cells with a strain of HIV-2. When all three strains were assessed for major proteins in the retroviral genome and long terminal repeats, it was discovered one of the strains (from an uninfected individual) matched SIVsmm more closely than any HIV strain discovered previously. Upon further examination, when the HIV-2 strains were compared with SIVsmm, it was indicated that the two strains formed a single phylogenetic group of lentivirus; thus, confirming the link between SIVsmm and HIV-2.
On a viral genetic level, HIV-2 and SIVsmm are considered a match due to the correlation between viral genetic material in the HIV-2 and SIVsmm strains. HIV-1, on the other hand, is not quite as clear as far as viral genetic link. HIV-1 is believed to be a mosaic of multiple SIV strains. In one of the first SIVcpz strains to be characterized, SIVcpzANT, it was confirmed to have a vpu gene that was discovered in a divergent HIV-1 strain (Santiago et al. 2002). SIVcpzANT resembles HIV-1 on a genetic level, however, it is impossible to determine the location where SIVcpzANT may have originated from as it was detected in a chimpanzee in the Antwerp Zoo whose geographic source was unclear.
As the links between HIV and SIV have become clearer, one hypothesis has provided an alternative origin for HIV. It is thought that in the late 1950s, oral polio vaccines with materials extracted from primates were the cause of the HIV virus (Blancou et al. 2001). These vaccines were believed to have caused a mutation which led to the development of the viral strain. The areas where the first tests of polio vaccines occurred were also the very same areas in which AIDS was first discovered. However, it is widely thought the genetic origin of HIV-1 predates the same time as some of the earliest polio vaccines (Hahn et al. 2000). Thus, the probability of the polio vaccines’ viral strain mutating into an entirely new virus is highly unlikely, given that it did not exist at that point. Furthermore, no support has been provided to maintain chimpanzee tissues were used in the creation of the vaccine (Blancou et al. 2001). The odds of the oral polio vaccine hypothesis being the source of HIV is unlikely, based on the incongruity in timeline and no evidence to support the claim of using chimpanzees.
While the link between HIV-2 and SIVsmm is clear through the polymerase chain reaction study performed by Gao et al. (1992), it does not exactly explain how the jump from sooty mangabey to human was made. Among the many explanations, the most likely hypothesis is a zoonotic transfer from sooty mangabey to human. It is posited by Hahn et al. that HIV subtypes arose from cross-species transmission events which may include human cutaneous or mucous membranous exposure to contaminated sooty mangabey blood (2000). For instance, in more rural areas, individuals were likely to hunt bushmeat (including non-human primates) which may have been contaminated with the virus. Then, when a hunter was cutting open the bushmeat, he may have accidentally cut himself and became infected.
Despite this being the most popular hypothesis of transmission route from primate to humans, many still have lingering questions as to why it would happen now as multiple viral strains have been around for centuries. After all, bushmeat consumption has existed for centuries and SIVsmm is believed to have persisted for 100,000 years (Omenn 2010). Yet, the earliest evidence for HIV dates back to 1959 in a vial of blood at Emory University for a study on malaria (Hahn et al. 2000). If it is the case that bushmeat consumption and hunting were involved in transmission route, it seems much more likely that it would have happened at a much earlier time in history.
Part of the reason for the jump from primates to humans occurring when it did involves a basic understanding of biology. Over time, mutations tend to occur within genetic material because of specific selection pressures enabling SIV and HIV to survive. As the viral genome began to change, it eventually became able to transfer to humans and subsist within the human body as a result of mutations overcoming previous barriers (Platter 2009). Eventually, the “right” mutation occurred at the “right” time to be able to infect humans.
In addition to this, other pressures on humans occurred, making it easier for the SIV virus to cross-over and mutate into HIV. At the same time, for humans, working conditions in western Africa led to a decline in public health. During the time of some of the first HIV infections in 1959, Africa was in the midst of colonialism. Africans were forced into a cash economy system and hard labor practices to obtain necessary resources (Chitnis et al. 2000). As part of these labor practices, individuals often migrated to where jobs were located, typically resulting in a mixture of people from all over Africa, and thus, any diseases. Concurrently, infectious disease barriers were being broken down and individuals’ immune systems were weakened by simultaneous infections. Furthermore, many of these practices (such as creating railways) often encroached into primate habitats, thus, increasing workers’ exposures to infected non-human primates (Chitnis et al. 2000). Through the working conditions, many workers were given better access to infected primates—thus, increasing the chances of infection. Without the workers realizing it, many of their immune systems weakened, making the viral transmission more likely to transpire. Since these first infections, the disease has spread rapidly; currently, there are 33.3 million people worldwide living with HIV/AIDS (UNAIDS 2010). While the disease transmission patterns have changed over time, it still has a large prevalence rate worldwide.
Since the onset of the initial HIV epidemic, evidence has continuously come to light supporting the hypothesis in which HIV is a zoonotic virus originally occurred in non-human primates. These claims are supported through the similarities of the virus, locations of the virus, and genetic similarities between viral strains. Historical implications further enhance the plausibility of this situation which has become widely accepted throughout the scientific community. Because of this zoonotic disease, many researchers are beginning to give greater attention to emerging infectious diseases with zoonotic origins as human populations grow and affect climate change in wildlife. Although it is possible for HIV/AIDS to continue to mutate and evade biomedical treatment, as we begin to acknowledge the origins of the disease we may be able to find out more about the virus and begin to treat it more effectively.
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