Viral Sex



Viral Sex
The Nature of AIDS

Oxford University Press

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The Most Disarming Virus

In the early 1980s, a strange new epidemic emerged among North American homosexual men. It was first seen in the large gay communities of New York and California among young men who were very sexually active. These men became mysteriously ill with infections and tumors that, according to previous experience, were rarely serious and rarely combined in the same individual. Certainly they had never been seen in epidemic proportions in such a narrowly defined risk group.

One of the infectious agents was Pneumocystis carinii, a usually harmless microorganism that thrives around us and even inside of us. Like many other organisms in our environment, P. carinii routinely colonizes most of us, at an early age, with no ill effects under ordinary circumstances. Colonization of one organism by another--also called infection--quite often causes no disease. Although P. carinii had been known to cause serious and sometimes fatal pneumonia in humans and other animals, this happened only in circumstances of abnormal weakness. It might harm malnourished children or severely ill people with a lowered capability to fight infections, but not vigorous young men.

The same was generally true for Kaposi's sarcoma (KS), the tumor most often seen in the new epidemic. This cancer is recognized by bluish red skin lesions that usually appear first on the feet and lower legs. The lesions tend to spread upward on the body, and may also spread inward from the skin, especially to the lymph nodes. KS had previously been seen in aging men in the United States and Europe, but it was uncommon and rarely aggressive. It was more frequent and serious in Africa, but still no great threat.

What was going on among these young gay men? Physicians who treated them in San Francisco, Los Angeles, and New York soon found that they suffered massive immunodeficiency. Some impairment of the immune system that normally protects us from invaders had allowed the bizarre and fatal combination of infections and tumors. The condition was marked by a rapid decline of certain blood cells, or T-helper cells, whose cell wall includes a crucial molecule known as CD4.

These CD4-positive cells are major players in our immune system. CD4+ cells are essential to fight all types of invaders. In this epidemic, their impairment was apparently not inborn but somehow acquired, so the disorder came to be called AIDS: acquired immunodeficiency syndrome.

How had these young homosexual men acquired such a severe immune disturbance? Clues began to come from the US Centers for Disease Control (CDC) in Atlanta, Georgia. The CDC found that those who developed AIDS had invariably had sex with someone who concurrently had AIDS or later developed the disease. Apparently it was transmitted sexually, most likely by means of seminal fluid.

Then AIDS began to occur among hemophiliacs, but not by sexual transmission. Hemophilia is a congenital disease, seen only in men, in which the blood does not clot normally. It is effectively treated with transfusions of blood that contains clotting factors, but apparently blood could also transmit AIDS. This transmission route was later confirmed when AIDS appeared among intravenous drug users who had shared needles with infected gay men. Intravenous (IV) drug use and needle sharing are not uncommon among the most sexually active gay men, who often combine certain drugs with sexual relations.

The transmission of AIDS in semen and blood, its epidemic spread, and its sudden occurrence in otherwise healthy men suggested an infectious agent, probably a virus. In 1982 or 1983, only two years into the epidemic, a likely suspect was found at the Institut Pasteur of Paris by Francoise Barre-Sinoussi, Jean-Claude Chermann, Luc Montagnier, and colleagues. The new virus was discovered in an enlarged lymph node taken from a young homosexual man. He had not yet developed AIDS, but AIDS patients were found to have the same virus in their blood.

In 1984, American researchers Mika Popovic, Bob Gallo, and colleagues showed that most AIDS patients had this virus, while a control group of healthy subjects did not. (With today's finer techniques, they would have found the virus in all their AIDS patients.) Meanwhile, the virus infected three lab workers who later developed AIDS. As far as most scientists were concerned, this tragedy supplied the last piece of the puzzle. According to a reasoning process based on Koch's postulates, an agent is linked to a disease in four steps. First, the agent is observed in every case of the disease. Second, it is isolated from people with the disease, then grown in pure culture. Third, the culture causes the disease when inoculated into susceptible subjects (in this case, the unfortunate lab workers). Fourth, the agent is observed and recovered from the experimentally infected subjects.

Some problems would later arise from this early work of the French and American groups, as discussed in Chapter 2. But these researchers identified the new virus, and the Gallo team grew the virus to high levels of infectivity, enabling rapid production of kits to diagnose the infection. The virus was soon known as HIV: human immunodeficiency virus. Perhaps no other virus in history has become so widely known in so short a time.

But what exactly is a virus? Why is HIV so especially deadly? Viruses are infectious agents like bacteria, but they are far smaller and unlike bacteria, not self-sufficient. They are parasites that need a host, like mistletoe needs the oak tree. They can often exist on their own, in a kind of suspended animation, but to reproduce they must use and subvert the mechanisms of a host cell. Some viruses can thrive in only one type of cell within one type of plant or animal. Others are not so fussy. HIV prefers certain T-helper cells and macrophages of the human immune system. (Macrophage means "big eater" in Greek because these defender cells neutralize invaders by engulfing and digesting them.) HIV enters its chosen cells through the CD4 molecule mentioned earlier. This crucial discovery was made simultaneously by two groups: David Klatzmann, Jean-Claude Gluckmann, and collaborators in Paris, and Gus Dalgleish, Robin Weiss, and coworkers in London.

Of course, CD4 does not exist solely to give passage to HIV. It did not evolve to serve as the HIV receptor or welcome mat. In fact, its main job is sentry duty: it recognizes intruders and arouses various fighter cells against them. In an ironic twist, HIV uses this guardian molecule to enter and ultimately destroy the cells that carry it on their surface. To ensure its own survival, HIV defends by attacking: it cripples the immune system that would destroy or control it. Its effects are slow to show because, up to a point, the cells it destroys can be replenished. But eventually its steady killing reduces the quantity and quality of CD4+ cells, causing immunodeficiency. By the time people have full-blown AIDS, they cannot cope with invading organisms that normal people accommodate or fight off every day.

The organisms that threaten AIDS patients are not only invaders from our external environment but insiders like P. carinii. These members of our internal ecosystem--our natural flora--are usually kept in their place by many factors, including a healthy immune system. But given the opportunity to overgrow or grow in the wrong place, they can cause "opportunistic" infection. Several studies of the natural course of AIDS have shown that certain opportunistic infections always become fatal once HIV is acquired and persists in the blood and other organs of the body.

Where did this treacherous and apparently new virus come from? As the Bible says, "There is no new thing under the sun." HIV may be truly new, but it is more likely an old virus that has gained a new level of virulence, enabling it to cause human immunodeficiency. Or perhaps it has always been virulent but has only now entered the human species.

If so, what animals previously harbored this virus, and where on earth? Why have we not seen AIDS-like disease in these animals? Is AIDS unique to humans? Has the disease appeared before, sporadic and unrecognized, or is it entirely new to this century? If sporadic in the past, why is it suddenly a raging epidemic?

Many questions occur, but the quintessential ones are: Why us and why now?

When AIDS was first seen in North America and then in Europe and Africa, epidemiologists were baffled. Most epidemics can be traced to one focal point, but this one seemed to be spreading independently on three continents. North American and European AIDS were soon regarded as one epidemic, brought to Europe from America by gay men. (As noted in Chapter 2, evidence now shows it traveled the opposite way.) Meanwhile, a different type of AIDS surfaced among a few central Africans living in Belgium and France. This disease was transmitted heterosexually, appeared mainly in women, and had come directly from Africa.

Today AIDS is generally accepted to be more than one epidemic caused by a whole family of HIV types, subtypes, and strains. The main epidemic in North America and Europe is caused by HIV type 1 (HIV-1). Now spreading fast to South America, this Western HIV is apparently becoming ever more lethal or virulent as it is passaged through the human population. That is, it gains strength each time it enters a new person, reproduces in the CD4+ cells, then bursts out to circulate and infect another person.

Unfortunately for us, this process of cycling to virulence seems to be an HIV family trait. (Both virus and virulence stem from Latin virus, meaning "poison" or "venom.") All members of the family, including HIV-1, were probably much less deadly when they first encountered humans. They had to reach a threshold of cycles and new infections before they could cause AIDS and premature death. If so, then HIV may have been with us for millennia. It can suddenly cause AIDS because of some change in us or in its own makeup. For example, HIV may only recently have acquired the mutations or genes to cause human immunodeficiency.

If HIV virulence rises with new infections, are there some types among us that do not yet cause AIDS? So far, research indicates that all members of the HIV family can cause AIDS (some faster than others)-but a very few people can block the disease. We have seen two of these lucky individuals in an Amsterdam study of men infected since 1983. Our study began with a sample of more than one thousand gay men, who were examined every three months. These subjects belonged to the subgroup known to be at highest risk for AIDS: young gay men who seek rough and anonymous sex with multiple partners. Some of the sample were HIV-infected before the study began, but we focused on those who became infected as the study proceeded. These men, who so far number about fifty, have now been followed for an average of ten to twelve years.

As usual with HIV-1, each case started with acute infection. Though brief and sometimes hardly noticeable, this flulike illness was accompanied by the generation of permanent and specific HIV antibodies. Our immune system normally greets any invader by producing specific antibodies. They remain forever on call, should the invader reappear. If it does, they are geared to recognize and tag it as an enemy to be destroyed. HIV antibodies are evidence of seropositivity. Their appearance signifies seroconversion: the first point at which serum is found to contain the virus, its genetic material, or antibodies to the virus. (Tests that show a person to be HIV-positive usually detect antibodies. They are indirect but long-lasting evidence of the virus. Their persistence tends to make them more reliable as evidence than the virus itself or its genetic material.) The acute stage was followed by a period free of symptoms or disease, which usually lasted several years. But of those infected early in the study, more than 75 percent have now developed AIDS, and twenty-three have died. Three individuals developed the disease within only eighteen months of initial infection. At the opposite end of the spectrum, the two lucky ones still show no sign of immunodeficiency.

Incidentally, our work offers further proof that HIV is the agent of AIDS. Of the twenty-three men who died, each acquired HIV infection before development of any immune disturbance. And not a single case of AIDS--or any sign of immunodeficiency--has developed among the many hundreds of men who have remained HIV-negative over the years. However, a few researchers still doubt HIV is the agent of AIDS. One of their arguments is that Kaposi's sarcoma has occurred, though rarely, in young gay men with no sign of immunodeficiency. As noted in Chapter 4, recent evidence indicates that a newly discovered virus, sexually transmissible but unrelated to HIV, may be involved in KS. And while KS can occur without HIV, it clearly runs a much more aggressive course in HIV-positive people.

Based on the linear progression of AIDS development, we can now extrapolate that about 95 percent of homosexual men infected with HIV-1 will eventually develop AIDS. Their symptom-free period will vary according to a bell-shaped curve (Figure 1.1). Very few individuals will develop AIDS in the first year after infection or in the "last" year, projected to be fifteen to twenty years after infection. Most people will progress to AIDS after an average asymptomatic period of about ten years.

The data suggest that our two nonprogressors remain well not because of virus variation but because of host variation. In other words, these men did not get an unusually weak virus but are, for some reason, unusually well defended hosts. All of us are genetically programmed to offer a more or less effective immune response to HIV and other invaders. The response to any invader involves many factors, all of which can vary. With HIV, an important variation is seen in the cells that carry the CD4 molecule. From person to person, these cells are more or less hospitable to HIV access, entry, and multiplication. Our two AIDS-free subjects have maintained extremely low levels of circulating virus since their initial infection. In contrast, subjects who have developed AIDS quickly have had extremely high levels during the entire period. Naturally, we are looking hard for the precise factor that seems to protect the nonprogressors.

More clues to virus and host variation can be found by comparing HIV and AIDS in the three major risk groups: homosexual men, IV drug users, and hemophiliacs. All three groups are susceptible to HIV-1, but they differ in their AIDS frequency rates and their length of symptom-free periods. AIDS occurs at a somewhat higher rate among gay men than among IV drug users and hemophiliacs, even though the sexual transmission of HIV is far less efficient than its transmission by injection.

For IV drug users and hemophiliacs, certain host factors are known to lower AIDS frequency and lengthen the symptom-free period. All other things being equal, the younger a hemophiliac, the better his defense against AIDS. As for drug users, the frequent sharing of syringes means frequent exposure to HIV. However, once infected, they derive a small benefit from this dangerous practice. The constant injection of foreign blood seems to dull or confuse the immune response, leading to cell anergy (the opposite of energy), which slightly curbs reproduction of the CD4+ cells. This, in turn, slightly curbs multiplication of HIV, since the virus depends on host reproductive mechanisms.

Much evidence indicates that host factors, more than virus factors, are responsible when HIV is thwarted; conversely, host factors are less responsible when the virus thrives. All HIVs seem to be viable and virulent, and some have found ways to increase their damage. For example, some HIV-1 strains seem able to change their envelope to facilitate entry into CD4+ cells. They can also mutate the genes that regulate their multiplication, to step up the rate. So HIV needs no help from a weak defense, but apparently it can be slowed by a strong defense. One may say that increases in the rate of disease progression are more virus-dependent, while decreases are more host-dependent.

If all known HIV types have gained the virulence to cause AIDS and death, is this virulence now increasing or decreasing? Does the HIV of the Western epidemic cause AIDS faster now than in the early 1980s? Preliminary evidence is discouraging at first glance. A collaborative study of homosexual groups in San Francisco, New York, and Amsterdam showed that men infected during the first five years of the epidemic remained healthy longer than those infected during the second five years. This suggests that HIV virulence had increased in these gay communities.

The good news is that virulence seems to have dropped slightly since then (Figure 1.2). Of course, even the fastest acting AIDS usually takes four to six years to develop, so most Amsterdam men in our first five-year group were infected soon after HIV entered the community in 1980. The second five-year group was infected in the mideighties, at the peak of sexual activity and HIV infection among Amsterdam homosexuals. Since that high point of 1984-1985, when HIV incidence (i.e., new infections) was 8 percent, the incidence among these men has steadily declined. It had dropped below 1 percent in 1993. Over this same period, HIV circulation has decreased along with high-risk sex. Because of educational programs and other factors, many gay men in Amsterdam have reduced the number of their sex partners and their episodes of unprotected anogenital contact.

Both types of reduction lower the risk, but particularly the latter. Whether sex is homosexual or heterosexual, the probability of acquiring HIV-1 is related less to promiscuity than to the type of contact and the sex of the partner. Especially among men who have sex with men, the number of partners is far less important than the kind of sex they practice.

The most dangerous sex is anogenital: anal penetration by the penis. The more often an uninfected man is anally penetrated by a man infected with HIV-1, the greater his chance of acquiring HIV and AIDS, whether his partners are few or many. Limited studies of heterosexual couples in Africa suggest a parallel, at least with regard to some HIV-1 strains. That is, the more frequently an uninfected woman is anally penetrated by a seropositive man, the greater her risk, whether the situation is monogamous or polygamous.

The safest sex is that between two women, even if they engage in anal stimulation. In fact, two women engaged in such contact (i.e., nonpenile but involving some kind of penetration) are at less risk than two men engaged in the same type of contact, possibly because force is less often a factor. The more forceful the anal penetration, the more likely it is to cause lesions, which invite infection.

We are very encouraged to see that safer sex may have reduced not only new HIV infections but HIV virulence in Amsterdam. Preliminary data from our Amsterdam cohort studies show that men newly infected when circulation had dropped (from 1989 to 1993) are progressing more slowly to AIDS than men infected when HIV circulation was highest (from 1984 to 1988).

Much evidence suggests that HIV virulence, or damage, is directly related to its rate of circulation. This is because the virus load needed for efficient HIV transmission depends on virus reproduction within host cells that are crucial to host well-being. As already noted, the faster and more often HIV changes hosts, the more deadly it becomes. Our own studies have shown that the virus is more aggressive in times of rapid spread and less aggressive when spread is relatively slow. Spread depends on two factors: the opportunity to transmit HIV and the infectivity of the virus. Opportunity depends on the frequency of the transmission event, whether it is unprotected sex, blood transfusion, or IV drug use. Infectivity depends on the level or amount of virus in the transmitting fluid as well as the susceptibility of the host cells to that particular virus.

Looking at sexual transmission (by far the most common of the three routes), we have seen that virtually all newly infected individuals have high virus loads during the first few months (Figure 1.1). As measured by the HIV RNA in their blood, they have about equal amounts of circulating virions, making them equally HIV-infectious. But soon a distinction develops between progressors and nonprogressors (i.e., those rapidly progressing to AIDS and those progressing slowly or not at all). The progressors are highly infectious due to persistent high virus loads in all their body fluids. They transmit a highly aggressive virus that reproduces fast and sustains high levels in its next host. However, progressors are highly infectious for a relatively short time due to rapid disease progression. As their CD4+ cells fall, their sexual activity tends to decline because they feel increasingly ill and develop unattractive symptoms: the dark red Kaposi lesions, the continual cough of P. carinii pneumonia, or devastating diarrhea.

In contrast, the nonprogressors are less infectious for a relatively long time because the virus load declines in their fluids. As their immune systems keep AIDS at bay, they feel healthy enough to continue sexual activity, but they transmit a weaker virus. It reproduces relatively slowly and cannot sustain high levels in the next host. Of course, as the epidemic continues, the progressors with their aggressive HIV contribute less and less to the viral mix. They drop out of sexual activity and ultimately die. Therefore, we see that a new AIDS epidemic is dominated by the more infectious virus of progressors, but a late-stage epidemic is dominated by the weaker virus of nonprogressors.

At times of high spread, the stronger virus shrinks the average symptom-free period because it needs less time to break down the immune system. At times of low spread, the weaker virus leads to a longer average symptom-free period. We have compelling evidence that breakdown occurs faster when HIV is acquired (by any route) from an AIDS patient whose symptom-free period was relatively short.

These observations are based on various studies but particularly on our own work in Amsterdam. This has involved a highly active subgroup of relatively young gay men whose sexual habits--and the spread of HIV in their community--have changed rapidly over a short period. Although many gay men have stable long-term relationships, this highly active subgroup combines youthful potency with militant expression of emancipated homosexuality. Their motivation is understandable, but their frequent and anonymous sexual contacts (sometimes several in a day, or several hundred in a year) have given the Western HIV a golden opportunity. At times of high spread, the virus may be introduced by one man to another who, the same day or soon after, conveys it to a third man, and so on. In New York, one man was simultaneously infected with two HIV strains by two different partners within just a few days.

Such promiscuity, practiced routinely throughout a good-sized community, may be unprecedented in history. It may be approximated by heterosexual men who continually visit many different prostitutes, but such men are rare, as far as we can tell. For one thing, prostitutes cost money. In contrast, gay encounters in bathrooms and bathhouses are largely free of charge. It is a tragic accident that HIV-1 was introduced to a population where such activity--so perfectly suited to its passage!--had become the hallmark of liberation. This first HIV epidemic got off to a very good start.

Fortunately, as shown in Amsterdam, preventive measures can reduce HIV infections and actually reverse the spiral of aggressive infection. Fewer people get HIV and AIDS. They stay healthier longer because the virus is weaker and gives them a longer symptom-free period.

However, HIV remains. Now that it has found us, we are locked in a dynamic relationship with this virus. We have seen the benefits of lower HIV circulation, but to sustain those benefits a population such as the Amsterdam gay community must keep the dangers in mind. Members of such a community need to know that they can take control and reduce the threat. Then, having done so, they must remain on guard. If they feel more healthy, see less illness and death, forget the risk, and return to risky behavior, they will quickly revive the threat. To keep HIV in check, everyone who is sexually active--gay or straight--must avoid the high-risk behavior that gives HIV the advantage.

If the virulence of HIV fluctuates with its level of circulation, what does this mean for the worldwide future of AIDS? An infection, harmful or not, can pass through three stages: sporadic, epidemic, and endemic. A sporadic infection makes a scattered appearance and may disappear without ever becoming widespread--or it may progress to the second or third stage. The words epidemic and endemic, like democracy, are based on Greek demos, "people" or "region." The prefix epi- means "over, on top of," so an epidemic spreads over an area. The prefix en- means "inside of," so endemic implies deep roots. An epidemic infection may eventually disappear--but it may progress and become endemic, like cholera in India. Once endemic, it is part of the landscape and is very hard to eradicate although disease, if any, may actually be milder than when the infection was sporadic or epidemic. (While epidemic, endemic, and population began as human terms, this book will follow general usage and apply them also to nonhumans, avoiding such animal-specific terms as epizootic and enzootic.)

In North America and Europe, AIDS is epidemic but seems to be holding, and HIV-1 incidence has dropped (Figure 1.3). In South America and Asia, the disease is fast reaching epidemic proportions. It could easily become endemic because of factors such as poor education, communication, and medical care, which have already made it near endemic in much of Africa. HIV incidence is rising in South America, Asia, and Africa. Several HIV types and subtypes are involved, but if the whole HIV family thrives on circulation, we must expect increasing virulence everywhere, especially in relatively deprived areas.

Since the HIV-1 subtype circulating in North America and Europe is already quite deadly (killing more than 90 percent of its victims within fifteen years), one might ask how it--or other HIVs--could become even more deadly. Evidence suggests that it could kill faster. It could shorten the symptom-free period that follows the initial acute infection. If so, instead of developing AIDS over several years, people might develop the disease in a matter of months. We would then see many millions more cases of AIDS than are projected on the basis of today's average disease-free period.

At this time a very small fraction of infected individuals develop AIDS less than one year after infection. But this could change, as shown by studies of monkeys. Many African monkeys carry a virus closely related to HIV. By analogy, it is called simian immunodeficiency virus (SIV), though it does absolutely no harm to its African monkey hosts. However, it harms Asian monkeys. This was discovered when African and Asian monkeys, imported to the United States for laboratory use, were housed together. Suddenly the Asian monkeys contracted a fatal AIDS-like disease. Researchers later found that certain SIV strains could kill Asian monkeys in as little as several weeks or months. These lethal strains had been developed in the laboratory by rapid passaging through many monkeys: SIV-infected blood from one monkey was injected into another, whose infected blood was injected into another, and so on.

Could this kind of virulence develop among humans? Outside Europe and North America, AIDS spreads mainly by heterosexual relations, perinatal infection, and contaminated blood and hospital supplies. Control strategies must aim to safeguard the blood supplies and hospital equipment. But if HIV thrives on rapidity of consecutive transmission, these strategies will not be enough. Somehow people in Africa, Asia, and South America must be educated to lower their number of sexual partners and, even more important, their high-risk sex acts. Gay men in Amsterdam and other areas have shown this can be done. Other strategies will be described later in this book.

Even in North America and Europe, where HIV incidence is dropping, we cannot rest easy. The decreased incidence may lead to decreased virulence and even to a weakened or attenuated virus. But virulence could just as well be boosted by ominous changes in the Western epidemic. At first HIV-1 was spread mainly by homosexual relations, then by needle sharing among drug users. Now it is infecting more women and children, most of whom have no direct connection with drugs or homosexuals. HIV infection is seen mainly among the poor and homeless in big cities like New York, but it could easily become a more general threat. The Western epidemic, like those elsewhere, could gain momentum by spreading heterosexually as well as homosexually.

Ultimately HIV is a threat to us all, everywhere in the world. We can all agree that something must be done, but how do we disarm this virus that disarms us so well? How can we render it less aggressive, even harmless?

Nature and science will ultimately show us the way, but two promising avenues have so far been disappointing. The first involves searching the HIV family for types that are relatively harmless, either because of inherently low infectivity or loss of infectivity (attenuation). Such relatively weak viruses could give insight into more harmful types. They might even protect us against them, as cowpox was used by Jenner to protect against smallpox.

At this point, we have discovered and studied two possibilities that will later be discussed in depth. The first is HIV type 2 (HIV-2), which emerged in the West African interior. This virus causes AIDS, but very slowly and with lower frequency than HIV-1. HIV-2 is mainly confined to West Africa, where HIV-1 subtypes are appearing with increasing frequency. More time and study are needed to tell how well HIV-2 infection protects people against HIV-1. Although most West African AIDS victims harbor only one of the two viruses, a rare few harbor both. This could mean HIV-2 offers incomplete or temporary protection. However, with a double infection we cannot yet tell whether the two viruses entered simultaneously or, if sequentially, which came first. We can still hope that HIV-2 has some protective potential, and new data point tentatively in that direction.

Meanwhile, HIV-1 is overtaking the slower HIV-2 in West Africa, but HIV-2 is not likely to disappear. It has a proven monkey reservoir or home base: the sooty mangabey. This monkey comfortably hosts an SIV that becomes HIV-2 when transmitted to the human body. Such transmission has been documented on several occasions. It may even occur quite frequently, as when monkeys bite--or are eaten by--humans.

The other new type to be studied is HIV type 0 (HIV-0). It was discovered in 1990 by Belgian researchers Guido van der Groen and Peter Piot, who initially thought they had found HIV-3. Their virus seemed unrelated to HIV-2, which was discovered in 1985 by Francois Clavel, Luc Montagnier, and colleagues. It also seemed unrelated to HIV-1 but is now considered a distantly related HIV-1 subgroup. Some have called it "O" for "outgroup," but "zero" is now preferred. Originally found only in Cameroon and Gabon, HIV-0 was isolated from several AIDS patients by different researchers, leaving no doubt that it can cause the disease in humans. Its virulence is unknown, but its spread is extremely limited. The virus has just recently been seen in Europe, mainly France, in a handful of immigrants from Cameroon and Gabon. In Africa, it is only rarely seen outside its accustomed area. Even there, HIV-0 occurs in much less than 10 percent of AIDS victims. The rest are infected with the more common HIV-1 subtypes.

As with HIV-2, the closest relative to HIV-0 is not another human AIDS virus but a monkey virus. Found in chimpanzees, it is called chimpanzee immunodeficiency virus (CIV) or, more often, SIV cpz. Like other SIVs, it does not harm its natural host. Very few chimpanzees in the wild seem to harbor this virus, but its transmission to a human has occurred at least once, and maybe more.

While HIV-2 and HIV-0 have great research value, they are not too promising as barriers against HIV-1. Though they spread and act slowly, they still cause AIDS. As long as an HIV type destroys our defense system, it is a deadly virus sooner or later. We want one that will protect us while causing little or no immunodisturbance--but perhaps no in-between exists for HIV. This virus may have evolved so that its multiplication in humans always decimates the immune cells to a fatal degree. In fact, one might question whether HIV-0 and HIV-2 are that different from HIV-1. Perhaps they are only in different equilibrium with their host populations, most likely because of host factors such as sexual partner rates.

Our second avenue is to find a virus outside the HIV family: something similar but harmless to its natural host. We have already found CIV, other SIVs, and even analogs beyond the primate family. As discussed in later chapters, these viruses offer tantalizing clues to the HIV family. But so far, none offers us protection from HIV. Although closely related to the killer, these viruses are remarkable in that they never cause the slightest harm to their natural hosts. SIVs can even move among various types of African monkeys without harm. In fact, they seem to inhabit a different virus world than our HIV. Without knowing the terrible AIDS story, we would never believe that these innocent monkey viruses could kill. Yet they kill humans, and some of them kill Asian monkeys.

What makes these simian viruses perfectly harmless to some primates and deadly to others? How can they be so well adapted to multiply in human immune cells? Since we find no harmless HIVs, it appears that SIV just naturally develops into an AIDS-causing pathogen after roaming from human to human for a number of viral generations.

(C) 1997 Oxford University Press, Inc. All rights reserved. ISBN: 0-19-509728-9

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