Origin of HIV the Mystery of HIV

Origin of HIV

The mystery of HIV and its origins is one that cannot be easily solved. In the thirty-odd years which have passed since the official recognition of AIDS by the CDC and the subsequent search for its cause, various theories have been floated regarding its nature, its development, its ability to adapt, our ability to combat it, and -- most importantly for some -- its origin. How did the virus come into being? Viruses are known for altering over time and according to circumstances. They have a way of "bending" in order to make due -- of manipulating themselves in such a way so as to survive. This is no less true for HIV than for influenza. Just as variants of influenza appear each year to wreak havoc on the human population, variant-strains of HIV continue to be discovered, suggesting that the virus is still developing, still finding a way to out-maneuver medical science.

However, if it is possible to discover just how HIV came to be, it may be possible to find a better way to combat it. In the animal kingdom, immunodeficiency viruses are found in felines (FIV) and in simians (SIV). Strains of SIV, particularly in Africa, show a remarkable similarity to HIV strains, suggest to many researchers that the "missing link" in the HIV origin story does indeed have something to do with the simian species of primate mammals.

Discerning the precise "link," though, has been much more difficult than evaluating the development of HIV. Assessing the development of a virus requires only a skillful eye and an ability to document change, alteration -- each new manifestation of the virus as it transforms and adapts. Discerning the origin, on the other hand, is like solving the crime. It clarifies the "event" -- takes an abstract hypothesis and puts it into concrete terms. It provides times, dates, places, persons involved. Such certainty is highly unlikely to be discovered in the case of the HIV origin story. Yet, while there are many unknowns -- many variables and factors that fail to yield solid ground, the trail has not dead-ended. Plenty of headway has been made towards discovering the precise conditions surrounding the birth of HIV. Whether scientists will one day be able to isolate it to one incident -- a single event in time -- or whether the best they will be able to do is to suggest several likely scenarios -- this much remains to be seen. For now, the clues are being followed and a better understanding of the origin of HIV is coinciding with researchers' focus on the virus' development.

First Discovery

In 1981, a startling new infectious disease was named by the Centers for Disease Control (CDC). At the time, it appeared (in the United States) that those who contracted the disease were primarily young, homosexual males. Nothing quite like it had ever been seen. The symptoms were nothing really new. Those who had it underwent a rapid deterioration of health: they began to appear older than they really were; they lost weight, hair; they became extremely sensitive to mild and normally easily combated "opportunistic infections," which all too often appeared to physicians as the cause of the disease. Medics tried treating the various symptoms -- but an improper understanding of what was behind them made their attempts ineffective. What appeared to cancer-caused lesions on the face and arms were not merely cancer-caused lesions. What appeared to be a body's inability to combat ordinary infections was not merely as simple as that.

Moreover, those mostly affected in the United States by this immunodeficiency existed outside the mainstream culture: they were marginal, misfits, people whose ways of life did not necessarily gel with the socially-approved mores of the mainstream. By the mid-80s it was known as the "gay disease" or the "gay plague." It seemed to originate in people who preferred that style of living. Because that style was, at the time, still relatively taboo in American culture, a precise grasp of the nature of disease was far from being discerned. The answer to how it was transferred led thousands of unwitting medical patients to contract it through blood transfusions. Screeners were not yet in place to deal with this sort of virus. They soon would be.

The cause of the disease would later be identified as the human immunodeficiency virus, better known today as HIV. The disease was AIDS -- Acquired Immune Deficiency Syndrome, so-termed by the Centers for Disease Control the following year. It attacked the patient's immune system, the individual's built-in barrier against germs and viruses. It was like an enemy making Swiss cheese of one's fortifications. (Greene 2007:S94). In the face of an overwhelming inability to deal with reality of the problem (due to social stigma), it was years before its name was even really mentioned in the mainstream. It continued to fester on what was perceived to be the edge of society -- an edge probably being punished for its aberrations by a higher power. Yet, when the edge suddenly and decisively cut into the mainstream, normative portion of American society, a new awareness set in. AIDS was not going away. It was not a "gay disease." It was something that could infect anyone and that did, in fact, affect far more heterosexuals than homosexuals (Greene 2007:S94). Dealing with the virus became of utmost importance and the question facing those who wished to combat was two-fold: how did it originate, and how could it be stopped?

The first part of the question held just as much weight as the second, as researchers attempted to address the problem of HIV.

Seeking Answers

The path towards the place where much of today's focus lies was not a direct one.

Initial investigations led researchers to a variety of premature conclusions: the disease was seen as the consequence of homosexuality and drug use (since it appeared in needle sharers as well). It seemed to only appear in an element of society that was already at risk for developing some sort of immunodeficiency syndrome. After all, there was nothing believed to be healthy about either drug use or homosexuality. This misconception, however, changed radically before the decade was out. New evidence began to emerge altering the perception of the immunodeficiency syndrome. One could look to the outbreak of AIDS in the island nation Haiti. Some suspected that perhaps the cause of the disease originated here. So, the magnifying glass swung from one subset of persons and individuals to another -- from homosexuals to drug users to foreigners. Yet, such speculation was almost fruitless and to no avail. Various explorations of particular groups of subjects led to the same dead ends: AIDS was not produced by the activities of any one group; it was not the effect of some way of life. But for some reason, these persons were particularly vulnerable. Why?

Perhaps the groups were worth another look, after all. Indeed, there was something that a study of each of these particular groups could show -- and that could be determined by assessing what it was that they had in common. In each of the sub-groups, there was the possibility for the exchange of bodily fluids -- the transmission of blood, whether sexually, intravenously, or through some other form of consumption. AIDS may not have been the result so much of living in a certain manner as the result of contracting something -- like a virus.

Indeed, research began to indicate that AIDS was transmitted through the bloodstream. (Sharp, Hahn 2011). It was a communicable disease, which grew not so much out of one's "deplorable" living habits but rather out of passing from one body to the next. Elizabeth Glaser proved that AIDS was not a condition that only homosexuals or drug addicts or Third World citizens could get. Elizabeth Glaser was an expectant mother: a woman who contracted AIDS during a blood transfusion (Greene 207:S94). She was someone from the mainstream, normative side of American life. And she was not alone. Like so many others, she contracted the disease because of faulty medical practices.

The supply of blood given to Elizabeth Glaser had been unknowingly extracted from an individual who carried AIDS. At the time, no proper method was available for testing for AIDS. It was not even known how to look for it. The screenings in place for sexually-transmitted diseases already known did nothing to indicate the presence of AIDS in the bloodstream. (On the contrary, AIDS was not typically identified in a person until the disease had already ravaged the individual's system past a certain point -- signified by the extreme loss of T cells). For Elizabeth Glaser, the virus passed from the blood donor to Elizabeth to the baby which grew in Elizabeth's womb. When Elizabeth and her baby died of AIDS, after having had no apparent connection to homosexuals, drug users or Haitians, a wave of insistence for greater AIDS awareness finally brought more focus to bear on the disease. National media turned its attention to the disease. Answers were demanded. Already, in the three years that had passed since the CDC's identification of the disease, some 15,000 persons had gone on to contract AIDS as a result of unscreened blood transfusions (Greene 207:S94). Clearly, the disease had appeared and been identified -- but safeguarding practices were yet to be put into place. Part of the reason was that no one really knew yet why or how AIDS developed and spread.

That knowledge would come within the decade as more and more studies into the nature of AIDS took researchers to Europe and from Europe to central Africa. AIDS was more than just an American epidemic. It was global. Studies began to pour in, which offered new evidence for how AIDS worked, what triggered it, and why. Researchers expanded their focus. New groups of people were admitted into the study.

In Europe, for example, two cases received much attention: one case concerned a pair of homosexuals. Viral strains began to be identified. The cause of the syndrome was beginning to be isolated. It was a virus of some kind. But why did it appear in such a broad swath of individuals all over the world? And where did it come from? The second case under scrutiny in Europe suggested a possible answer: It was this other pair which caused most interest: a group which showed no sign of involvement with any of the previously established group carriers (or of superficial involvement via transfusion). This pair was an immigrant couple from sub-Saharan Africa. Eyes shifted towards a new continent. Indeed, the pair pointed the way to a new dimension in AIDS research. Here was concrete evidence that something beyond homosexuality, drug use and blood transfusion was at work -- something that could possibly indicate that the virus was not the result of unnatural lifestyles, but of something else.

With a shift in focus, researchers suddenly discovered that African nations were swarming with AIDS. AIDS was a greater epidemic in this part of the world than in any other. Today, more than 20 million cases of HIV infections have been documented in Africa, as opposed to the one and a half million in the U.S. Or the 700,000 in Western Europe. For some reason, Africa was a hotbed for HIV -- a literal breeding ground for the virus. Why? What was happening in Africa that could possibly be triggering this explosion of HIV?

These questions had been posed on the micro-level but were no being posed on a macro-level. In fact, in Africa, it was already known as the "slim disease," because of the effect it had on the body (Greene 2007:S97). Now, however, the world understood it as AIDS -- and its cause as HIV.

Moreover, unlike in America, where social stigma was still heavily attached to the disease causing many to ask the wrong questions about its origin, in Africa the disease was commonplace -- but now beginning to come into the global spotlight (Greene 2007:S98). The standard of life was certainly different in the various African nations than it was in other industrialized parts of the world. Tribes still lived in parts of the continent, hunting animals and building grass huts. It was, in some regards, certainly a more primitive way of life. Did this primitive quality have something to do with the origin of HIV? In a way, yes. Scientists began noticing similarities between HIV and another immunodeficiency virus in simian primates in Africa.

For the first time it seemed like some questions were finally being answered. Now, scientists wanted to know: How long had HIV been in existence among them? Moreover, where did it come from?

First Clues

By the mid-1980s, researchers not only had a place to focus their inquiries into the origin of AIDS, they also had some knowledge of how the disease functioned. From all the information that had been gathered worldwide, some telling signs were standing out.

Researchers had begun looking for common findings within the various perspectives and approaches which they took towards the disease almost from the get-go. It appeared that in each of the studies, AIDS affected a group of T cells known as CD4 T cells (Sharp, Hahn 2011). A brief explanation of how AIDS developed helped scientists to connect the dots between it and other similar cases found in the medical textbook.

CD4 T cells, or T. helper cells, are white blood cells which assist the immune system by sending signals of attack to other cells. They may be likened to red flags used by a commander which convey the order to fire on an enemy combatant. T helper cells give the order to the body to defend itself from, for instance, viral infections. In a patient who suffered from AIDS, the patient had a reduced number of CD4 cells. This reduced number was what indicated to physicians the precise nature of the ailment. The patient was suffering from an autoimmune system failure. The cells meant to aid in the resistance of foreign invasion were malfunctioning. In fact, they were missing. If fewer than 200 CD4 T cells per cubic millimeter lived, the AIDS patient began to suffer from the very symptoms that brought the disease to the world's attention. In other words (and to use a rather simplistic analogy), the patient's defenses ceased to properly function; the walls were down; any and every infection could get through and nothing would tell the body to defend itself.

At this same time, researchers were focusing on a similar disease which was being studied and which also affected CD4 T cells. This focus identified a retrovirus which altered, rather than killed, T cells. The identification of CD4 T cell loss in AIDS patients suggested the possibility of a retrovirus at work. Moreover, this retrovirus appeared to be similar to a strain found in monkeys in Africa. Here was a tangible connection between the African immigrants affected by AIDS and a new virus similar to one found in African monkeys. Was there a connection between the viral strain found in monkeys and the disease killing humans all over the world? Was AIDS being caused by a virus? (The answer was yes: HIV would ultimately be identified as such a retrovirus. By 1986, HIV -- the cause of AIDS -- would be known) (Clavel et al. 1986:343).

The identification of human immunodeficiency virus brought applause from many corners of the globe (Greene 2007:S95). In the U.S., it was hoped that a vaccine would not be too far off. Yet, while the virus was now known, a way of combating it was not. Indeed, for as simple as the concept of HIV appeared to be, the virus was very resistant to various forms of treatment.

A greater understanding of the origin and the development of the disease could perhaps shed light on the reason the virus resisted vaccination. A closer look at HIV was needed.

Taking a Closer Look

As Sharp and Hahn point out, researchers began studying the relationship among the different viral strains which resembled one another. There was the simian viral strain and then the two distantly, it seemed, related HIV strains -- better known today as HIV-1 and HIV-2. HIV-2 had much more in common with the simian strain than HIV-1. Awareness of such a commonality was helpful in proposing an origins hypothesis: "human immunodeficiency virus type 2 (HIV-2), was only distantly related to HIV-1, but was closely related to a simian virus that caused immunodeficiency in captive macaques" (Sharp, Hahn 2011).

Was it possible that AIDS was the result of "cross-species transmissions" (Sharp, Hahn 2011)?

More studies into the virus that lived harmlessly in African monkeys were conducted. More viruses were discovered. SIVs, or simian immunodeficiency viruses, were identified in various sub-Saharan African nations and could be found in various simian species, ranging from chimpanzees to green monkeys (Sharp, Hahn 2011). These SIVs appeared to have too much in common with HIV-1 and HIV-2 for there to be any doubt that here was the answer to the question of the origin of AIDS: "These relationships provided the first evidence that AIDS had emerged in both humans and macaques as a consequence of cross-species infections with lentiviruses from different primate species" (Sharp, Hahn 2011). Somehow, monkey plasma and human plasma had intermingled in Africa.

The African Simian

A lentivirus is a genus of retroviridae. It is a virus that incubates in the host for a long time and can even spread to cells which do not divide. Both SIV and HIV were lentiviruses. But what was the connection? Did HIV stem from SIV?

To distinguish the several different strains of SIV from one another, a suffix indicating the simian species would be added to each strain of SIV. For example, the macaque monkey carried SIVmac. Yet, to complicate matters, each individual strain was not isolated to an individual species. Some strains occurred naturally in their host simians. Others occurred unnaturally. Again, SIVmac serves to illustrate the point: it did not occur naturally in the macaque monkey; on the contrary, later research indicated that it was produced when SIV strains from naturally-infected mangabey monekys known as SIVsm were introduced into macaques in America in order to help prevent the spread of disease. Here, prevention proved to be one step in the process of undoing (Apetrei et al. 2005:8991). What was naturally occurring in one species was not naturally occurring in another -- and now, thanks to U.S. practices, SIV was being transmitted from one simian species to another. Cold Spring Harbor Perspectives in Medicine published in 2011 a pictorial graph indicating the likely spread SIV to humans. In it, some of the various forms of SIV (fram Mandrills to Sooty mangabeys) were indicated, with a tracing of the inter-species transmission of SIV culminating in the various strains of HIV. Mangabeys, Mona monkeys, chimpanzees and gorillas all appear to play a decisive role in the transference of the immunodeficiency virus from simians to humans. How that transference took place must now be discussed.

Transference

"Viral fossils" indicate a history of the way that lentiviruses have evolved over the course of history. Records show that lentiviruses are able to pass from species to species. Other studies have shown that lentiviruses have evolved along with their African simian hosts for thousands of years (Sharp, Hahn 2011). However, because simians in Asia and America have not undergone extensive study, it is impossible to say how simians in these two sides of the world compare to their African counterparts.

Nonetheless, evidence exists which indicates that some lentiviruses in some species of simian may be passed to other simians and on yet again to other species, while other lentiviruses may be passed once from species to species but are not passed beyond the initial transmission (Van Heuverswyn et al. 1998:164).

The issue of SIV strains has become even more complicated, however, by the fact that different species have re-communicated strains to one another after those strains have mutated and adapted to the new host species. So a strain that may have originated in mandrill is now affected, for instance, by another species; the strain is then re-introduced into a mandrill, and the strain takes on another mutation. Souquiere et al. have named two separate and distinct SIV strains in mandrill monkeys in Africa. Their study even indicated that the mandrills could "represent a viral reservoir for humans similar to sooty mangabeys in Western Africa and chimpanzees in Central Africa" (Souquiere et al. 2001:7086). The close resemblance of the some SIV strains to HIV called for greater investigation into the relationship. Transference of SIV strains among simians in Africa was well-documented. Transference of HIV among humans worldwide was also well-documented (and by the late 1980s was even dispelling the myth that AIDS was a "gay disease," since 80% of all documented cases were amongst heterosexuals -- a point that came into light once Africa became a major focus of study) (Greene 2007:S95). But what accounted for the link between SIV and HIV? Was there more than a superficial connection? Does the pictorial graph published in Cold Spring Harbor Perspectives represent anything more than mere fancy?

Digging Deeper

Before attempting to answer the question of development, it is helpful to understand just how HIV operates. Research into the HIV genome revealed a rather simple makeup. Nonetheless, the nature of HIV's defense system is rather complex. Although it is a long-incubating lentivirus, it is very fast-moving once it enters a new host. Not only is it fast-moving but it also is able to "diversify" itself: Greene states that "a swarm of billions of different forms of HIV are present simultaneously in infected patients" (Greene 2007:S95). While researchers were racing to understand the virus and its ability to reshape itself once entered into the bloodstream, the need to establish some kind of perspective on the virus became prominent. Yet, as more and more details surrounding HIV came to light, the problematic nature of the disease increased.

HIV's ability to dodge any and all vaccinations was due to its "molecular gymnastics" (Greene 2007:S97). Nonetheless, of the simian strains, one has shown itself to be remarkably similar to HIV-1. This strain is known as SIVcpz -- the chimpanzee strain. According to Sharp and Hahn, SIVcpz is like "a complex mosaic" (Sharp, Hahn 2011). It appears to contain elements of a variety of SIV strains common to other simians. One theory for this "overlap" is that chimps have such an eclectic strain because of the fact that they will indeed prey on other simians (Goodall 1986:307). Interestingly, the transmission of SIVcpz from chimp to chimp was due mostly to sexual activity. The percentage rate of transmission was similar, moreover, to that of humans (Sharp, Hahn 2011). And, like humans, the strain could pass from mother chimp to baby chimp through the uterus.

The loss of T cells was also a fundamental find in the deceased chimp carriers of SIVcpz. These chimpanzees, originally thought to be able to carry the strain without suffering any of the effects of the virus, were now showing actually signs very much in line with humans who suffer and die from AIDS (Sharp, Hahn 2011).

Still, chimpanzees were not the only simians to offer a possible link between SIV and HIV. Wild gorillas also have also begun to show signs of filling that role as well (Van Heuverswyn et al. 2006:164). Upon analysis, SIVgor strains indicate that at some point within the past two centuries, a "chimpanzee-to-gorilla transmission event" occurred in which the SIVcpz passed into the gorilla species and mutated into SIVgor (Sharp, Hahn 2011). This find is, to date, unaccounted for: it is unknown how gorillas might have contracted the virus from chimpanzees. Gorillas do not prey on monkeys. Also, no in-depth study has shown whether or not SIVgor is fatal for gorillas who carry it (Sharp, Hahn 2011).

The HIV Lineage

When HIV was finally discovered in the mid-1980s to be the cause of AIDS, what was identified was really only one lineage of the virus. Because the virus is capable of changing when passed from one species to another, it is not surprising that to date four separate HIV strains have been identified. The first lineage has been identified as M. In 1990, the second was identified -- it was called O. Of all known cases of HIV-1, less than 1% of them fall into the O. group. Those that do mainly reside in Central Africa. In 1998, a third lineage was discovered -- and was named N. In 2009, a fourth -- P. Together, groups N. And P. make up just over a dozen reported cases of HIV infections worldwide (Sharp, Hahn 2011).

Each of these lineages, however, represents a deviation from the original source strain, which researchers speculate can be found in the SIVcpz strain. The "phylogenetic relationships" are close enough in the SIVcpz and HIV strains to warrant the speculation (Sharp, Hahn 2011). Unfortunately, researchers are unable to ascertain how the SIV came to be transmitted into humans, triggering the development of HIV. One theory is that SIVcpz entered into the human bloodstream for the first time as a result of "bushmeat hunting" (Peeters et al. 2002:451). But that is only one theory, and so far it is necessary to account for not just one HIV strand -- but four, with the latter two lineage groups coming into existence (speculatively) within the past century (Sharp, Hahn 2011).

As for HIV-2, which is mainly found in West African nations, there is some speculation regarding its origin. 1989 found researchers pointing to the sooty mangabey monkey as possible origin. The SIVsmm bears some similarity to HIV-2 and sooty mangabeys are routinely killed by West Africans -- so there is a degree of connection between humans and simians in this regard. However, while four lineages have been found in HIV-1, there are eight known lineages of HIV-2. Those eight lineages are defined according to groups A through H, with A and B. being the most common lineages.

In the United States, a new divergent strain of HIV-2 F. has been found. The individual lived in the same African territory where the F. lineage was first traced (Sharp, Hahn 2011). What is unknown, however, is whether this F. strain is mutating within humans or whether it is an altogether new strain that has resulted from a separate "transmission" event (Sharp, Hahn 2011).

While these questions remain open, the nature of HIV-2 does appear to be less deadly than HIV-1. As AIDS is identified once the number of CD4 T cells reaches the dangerously low level of 200 per cubic millimeter, HIV-2 does not attack these cells as aggressively as HIV-1; therefore HIV-2 carriers do not develop the same AIDS-like symptoms as those who carry HIV-1.

Problems Facing the Cross-Species Transmission

For SIV to become HIV, a number of problems must be overcome. First and foremost is the fact that both SIV and HIV require a great many proteins in order to grow and develop in the carrier. Both simians and humans "encode a number of host restriction factors" within their immune systems. This is what helps the immune system fight diseases -- like viruses. The nature of a virus is built upon getting around immune systems' defenses -- but get around them it must. The question is how. That is one researchers attempting to complete the link between SIV and HIV must be able to answer to convincingly ascribe the simian virus as the origin of the human immunodeficiency virus. Indeed, for an SIV to adapt to the requirements that a virus faces in order to develop in a human, it must significantly change its make-up (Sharp, Hahn 2011). Is this possible?

Wain et al. have indicated that a change has been seen in one protein code existent in several transmissions of HIV-1. This change with reference to the protein has been shown in SIVcpz and SIVgor. It has also been seen in HIV-1 (Wain et al. 2007). An infected simian could possibly pass the virus on to another different species if other conditions are right, as well. Sharp and Hahn identify "three classes of restriction factors" which must be broken down in order for SIV to pass from species to species (Sharp, Hahn 2011). The enzyme that halts "reverse transcription" must be neutralized; the protein that prevents "viral uncoating" must be stymied; and tethrin, which stops the virus from spreading must be rendered obsolete (Sharp, Hahn 2011). Each of these is important, complex, and involves a great deal of dynamism. Nonetheless, SIV appears to have dealt with each of them in turn.