The Coming Plague (66 page)
Authors: Laurie Garrett
Hahn concluded that SIVsm was probably a sooty mangabey virus that first infected rhesus macaques when the species were co-housed in captivity in a primate research facility or zoo, probably within the previous twenty years. And HIV-2, she averred, was derived from the mangabey virus. She suggested that mangabey-to-man transmission of the SIVsm was an event that had occurred periodically for decades, and still took place in the 1990s, as a result of scratches, bites, or blood exposures people experienced in West Africa while hunting the animals, transporting captured mangabeys, or butchering the monkeys and preparing their meat for human consumption.
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If the monkeys had carried SIVsm in days prior to colonialism, human exposure and HIV-2 cases might have occasionally occurred across a vast expanse, from Senegal to Ethiopia. But since the advent of colonialism the rain forest niches of sooty mangabeys had steadily undergone destruction, shrinking the animals' terrain down to a tropical jungle region of Central and West Africa, particularly Congo, Cameroon, Gabon, Liberia, Côte d'Ivoire, Sierra Leone, Guinea, Ghana, Burkina Faso, and Senegal. The postcolonial terrain of sooty mangabeys exactly matched the human HIV-2 region.
In 1993 the Smithsonian Institution's Natural History Museum in Washington,
D.C., extracted pieces of DNA from preserved monkey tissue in the museum's archives. They discovered that 57 percent of the wild-caught sooty mangabey samples, dating back to 1896, carried an SIVsm strain that was virtually identical to that found in 1971 and 1981 wild animal samples. That study proved that the monkey virus, which was essentially the same as HIV-2, had been prevalent in Africa for at least a century.
D.C., extracted pieces of DNA from preserved monkey tissue in the museum's archives. They discovered that 57 percent of the wild-caught sooty mangabey samples, dating back to 1896, carried an SIVsm strain that was virtually identical to that found in 1971 and 1981 wild animal samples. That study proved that the monkey virus, which was essentially the same as HIV-2, had been prevalent in Africa for at least a century.
And it begged a critical question: Why wasn't the human diseaseâHIV-2-caused AIDSâalso prevalent prior to 1980?
There was one notable epidemiological exception in the pattern of HIV-2 distribution in human beings: Pygmies. For millennia the Pygmy people had lived in the dense rain forests of Cameroon, Congo, and the Central African Republic, surviving as the continent's most expert jungle hunters. Monkey meat had always been part of the Pygmy diet, and the peopleâparticularly the male huntersâhad frequent, often combative, contact with simians.
Yet blood test surveys of Pygmy volunteers revealed no cases of HIV-2 or HIV-1 infection. Both the CDC (David Heymann and Pat Webb) and the Pasteur group (Françoise Brun-Vézinet) screened blood samples extracted from Pygmies during the late 1970s and again in the 1980s, finding no HIV carriers. That seemed to argue that HIV-2/SIVsm zoonotic flux was a relatively recent one, related in some fashion to urban lifestyles.
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Perhaps, scientists theorized, HIV-2 was a virus that had for decades gone back and forth between humans and monkeys, never evolving particularly well to meet the challenges of infecting either species. In a sense, they argued, HIV-2, SIVsm, SIVmac, and perhaps other simian viruses represented a large fluid genetic pool that shuffled about among a range of primatesâincluding
Homo sapiens
âin West Africa. In contrast, HIV-1 had become such a genetically specialized human killer that scientists were at pains to find ways to infect research monkeys and apes with it, and could not produce clear-cut AIDS in any nonhuman primate.
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Perhaps, scientists theorized, HIV-2 was a virus that had for decades gone back and forth between humans and monkeys, never evolving particularly well to meet the challenges of infecting either species. In a sense, they argued, HIV-2, SIVsm, SIVmac, and perhaps other simian viruses represented a large fluid genetic pool that shuffled about among a range of primatesâincluding
Homo sapiens
âin West Africa. In contrast, HIV-1 had become such a genetically specialized human killer that scientists were at pains to find ways to infect research monkeys and apes with it, and could not produce clear-cut AIDS in any nonhuman primate.
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As evidence mounted supporting Essex and Kanki's original assertions that HIV-2 was less virulent than HIV-1 (though they were wrong to conclude that HIV-2 was harmless), researchers began looking aggressively for evolutionary clues. Natural carriers of the various SIVs were unharmed by the viruses within them, and SIVagm, for example, was dangerous only when it spread from an African green monkey to another simian species.
If HIV-2 were the older, more highly evolved of the two AIDS viruses, then there ought to be many human beings who carried it harmlessly. Essex, Kanki, and MBoup believed that was the case, and their Senegal surveys certainly revealed that well over three-quarters of all HIV-2-positive people in that country were healthy.
In 1989 a German research group discovered a completely healthy woman from Ghana who carried a previously unidentified strain of HIV-2 that bore only 76 percent genetic homology with the classic HIV-2 strains found elsewhere in West Africa, and only 76 percent homology to SIVsm. The
group asserted that the Ghanaian HIV-2 strain represented something further back in the evolutionary chainâsomething close to a common ancestor of other HIV-2s, SIVmac, and SIVsm.
group asserted that the Ghanaian HIV-2 strain represented something further back in the evolutionary chainâsomething close to a common ancestor of other HIV-2s, SIVmac, and SIVsm.
“In our evolutionary tree, HIV-2alt [the Ghanaian strain] is closely related to this common ancestor and branches earlier than SIVsm/SIVmac and the HIV-2 prototypes,” said researcher Ursula Dietrich of the Chemotherapeutisches Forschunginstitut in Frankfurt. “It is still unclear whether the host of a common ancestor of the HIV-2/SIVsm/SIVmac group was human or simian ⦠. Because captive monkeys were injected with human material [in vaccine studies] back in the 1960s, artificial transmission from a human to a simian host could have occurred. It is possible, therefore, that SIVagm and SIVmac are fundamentally human viruses. In addition, the finding of HIV-2alt, a virus in a human which is evolutionarily older than SIVsm, could indicate that
all subtypes of the HIV-2/SIVsm/SIVmac group are of human origin.”
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all subtypes of the HIV-2/SIVsm/SIVmac group are of human origin.”
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In light of such discoveries, several means for human-to-monkey transmission of HIV-2 were suggested, including: tissue culture research in Europe and North America during the 1960s in which monkey and human cells were deliberately mixed, or human cells were injected into captive monkeys; and general export of simians worldwide, and those animals' exposure to human handlers on two or more continents.
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Most arguments, accusations, and scientific attention focused, however, on the more lethal HIV-1. And there, the waters were considerably muddier.
It wouldn't be until 1990 that a simian virus bearing significant homology with HIV-1 would be foundâin chimpanzees. A Pasteur Institute team, led by Simon Wain-Hobson, discovered SIVcpz in two out of eighty-three wild chimpanzees tested in Gabon. When the Paris group did molecular analysis of the SIVcpz virus they found that it was remarkably similar to several HIV-1 strains, and only distantly related to HIV-2 and all other known SIVs.
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In the case of two of the viruses' most important regulatory genes, crucial to the microbes' abilities to get into cells and reproduce (designated
gag
and
nef
), the chimp virus and HIV-1 had about 75 percent homology. Since within the world of all known HIV-1 strains major genetic groups often varied from one another by about 30 percent, the Gabon chimp virus was as similar generally to HIV-1 as the various subtypes of HIV-1 were to one another.
gag
and
nef
), the chimp virus and HIV-1 had about 75 percent homology. Since within the world of all known HIV-1 strains major genetic groups often varied from one another by about 30 percent, the Gabon chimp virus was as similar generally to HIV-1 as the various subtypes of HIV-1 were to one another.
Another SIV chimpanzee strain was found in Cameroon, and it was only 50 percent homologous to the Pasteur group's Gabon strain. That seemed terribly puzzling, until researchers discovered a bizarre HIV-1 strain among Cameroonian people, dubbed ANT70,
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or Type O. It was highly different from all other HIV-1s, but nearly identical to the new chimp virus.
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or Type O. It was highly different from all other HIV-1s, but nearly identical to the new chimp virus.
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In 1987, in an attempt to sort out confusion and keep track of the burgeoning genetic information on different AIDS viruses, the U.S. government's Los Alamos National Laboratory decided to dedicate some of its
considerable supercomputer space to a special GenBank AIDS project. At its helm, Dr. Gerald Myers kept track of the decoded sequences of every human and monkey AIDS virus in the world. In addition, GenBank became the repository for the genetic sequences of thousands of other species of organisms, as well as the discoveries of the Human Genome Project, an international effort to decipher the entire contents of
Homo sapiens'
twenty-three chromosome pairs.
considerable supercomputer space to a special GenBank AIDS project. At its helm, Dr. Gerald Myers kept track of the decoded sequences of every human and monkey AIDS virus in the world. In addition, GenBank became the repository for the genetic sequences of thousands of other species of organisms, as well as the discoveries of the Human Genome Project, an international effort to decipher the entire contents of
Homo sapiens'
twenty-three chromosome pairs.
Using computers to scan sequences for patterns and similarities, the GenBank group was able to construct a family tree, viral bit by viral bit. With PCR and the computerized telecommunications systems that allowed scientists to instantly relay their findings to one another and to GenBank, the AIDS viral files mushroomed in six years to include over 170 sequences, thus reaching proportions that gave Myers and his colleagues information that was statistically highly significant.
When the accumulated HIV-1 data was computer-analyzed, six distinct groups, or “clades,” emerged. Within clades the various types of HIV-1 differed by less than 20 percent. The clades were designated A through F, and scientists immediately saw that the various HIV subtypes clustered in distinct geographic areas.
For example, Type A was found in people in Central Africa and India. It was logical that a Central African family of viruses would make its way to India, as tens of thousands of Indians lived in the African region and regularly traveled to the Indian subcontinent. Type B was the only clade of HIV found in North America. Its members could also be found in Peru, Europe, Brazil, southern Thailand, and several parts of Africa.
The most lethal cladeâone whose members seemed to kill human beings with terrifying efficiencyâwas Type D, which was found almost exclusively in Africa's Lake Victoria region, encompassing Rwanda, Uganda, and Tanzania.
Within clades were so-called quasispecies, swarms of HIV types commonly found within individual AIDS patients, varying genetically by less than 10 percent.
And between the six clades, the GenBank group discovered, was a consistent 1992 variation of 30 percent.
When the GenBank group looked at viral strains collected in a given geographic location over a period of years they could see that HIV-1 was evolvingâor mutatingâat an overall rate of 1 percent per year.
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Assuming the 1 percent rate had been a consistent feature of the virus since its emergence, that would mean the clades had a common HIV ancestor that existed just thirty years prior, perhaps around 1962. And after ten years of mutating along a single course, the HIV family tree had spread out suddenly, yielding the six distinct clade lineages.
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Assuming the 1 percent rate had been a consistent feature of the virus since its emergence, that would mean the clades had a common HIV ancestor that existed just thirty years prior, perhaps around 1962. And after ten years of mutating along a single course, the HIV family tree had spread out suddenly, yielding the six distinct clade lineages.
Myers called this “the Big Bang,” a deliberate turn of the phrase used by physicists to describe the moment when the density of the universe reached critical mass, causing an inconceivably massive explosion that
generated all the nuclear subparticles and mass known to exist. On a humbler scale, Myers suggested that sometime in the early 1970s a biological event occurred that resulted in the sudden and explosive divergence of what had been a virtually linear evolutionary path for HIV-1. He could only speculate as to when and where that eventâwhatever it might have beenâoccurred.
generated all the nuclear subparticles and mass known to exist. On a humbler scale, Myers suggested that sometime in the early 1970s a biological event occurred that resulted in the sudden and explosive divergence of what had been a virtually linear evolutionary path for HIV-1. He could only speculate as to when and where that eventâwhatever it might have beenâoccurred.
Interestingly, the GenBank group's observation, based on viral genetics, that “something explosive” happened in the early 1970s coincided reasonably well with Project SIDA and Kapita's assertion, based on disease epidemiology in Central Africa, that a radical change took place in the region around 1975.
Beatrice Hahn's group, as well as the University of California, San Diego, team headed by Russell Doolittle, were convinced that the human virus was a distant descendant along a lineage that began with SIV in African green monkeys. Because all seven species of African greens carried the virus harmlessly, and some animals located in the wild over 1,000 miles apart had identical SIV strains, Hahn felt certain that the virus originated in the common ancestor of all African green monkeysâa species that theoretically inhabited the continent's rain forests over 10,000 years ago.
One disconcerting finding, however, was that African green monkeys in the Caribbean in the 1990s did
not
carry SIVagm. The animals were all descendant from two vervet monkeys brought from Africa by Spanish sailors to the islands sometime in the sixteenth century. If SIVagm was an ancient virus that had infected half the monkeys in the wild for centuries, it would seem logical that 50 percent of their Caribbean descendants should be infected. Desrosiers argued that the Caribbean situation could be due to a simple progenitor effect: if all the region's African greens were truly descendant from two wild monkeys, pure chance could have resulted in a Spanish sailor's selection of an uninfected pair of African animals.
not
carry SIVagm. The animals were all descendant from two vervet monkeys brought from Africa by Spanish sailors to the islands sometime in the sixteenth century. If SIVagm was an ancient virus that had infected half the monkeys in the wild for centuries, it would seem logical that 50 percent of their Caribbean descendants should be infected. Desrosiers argued that the Caribbean situation could be due to a simple progenitor effect: if all the region's African greens were truly descendant from two wild monkeys, pure chance could have resulted in a Spanish sailor's selection of an uninfected pair of African animals.
If SIVagm was the ultimate father of all SIV/HIV viruses, the lineage events between that monkey virus and HIV-1 were sparse and mysterious. The only HIV-1 clade that didn't fit Myers's “Big Bang” theory was Type O, the West African group that included the ANT70 strain, which bore striking similarity to SIVcpz. Hahn and Myers guessed that the Type O clade appeared well before the rest of the HIV-1s, perhaps decades earlier.
Going back even further in time, Doolittle's group compared the HIVs and SIVs to other so-called lentiviruses, showing that, as Doolittle put it, “HIV and visna virus [in sheep] are about as much alike as your average fungus is to a
Homo sapiens.”
Homo sapiens.”
But HIV was more akin to the sheep virus than to HTLV-1 and HTLV-II, once considered by Gallo, Essex, and many other American scientists to be the most likely candidates for either the etiology of AIDS or the ancestral origin of the AIDS virus.
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The availability by 1990 of advanced techniques for finding and analyzing viral genes hidden in samples of human blood or tissue prompted some
scientists to go back and reanalyze the oldest HIV-1 antibody-positive samples to see if the individuals were, in fact, infected with the AIDS virus.
scientists to go back and reanalyze the oldest HIV-1 antibody-positive samples to see if the individuals were, in fact, infected with the AIDS virus.
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