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June 1, 2006
Making the Link: Chimps Believed Source of HIV
by Tim Horn
May 25, 2006 (AIDSmeds.com)—Twenty-five years after the first AIDS cases were officiallydocumented, a new report published in Science indicatesthat researchers have isolated the source of HIV responsiblefor the global pandemic: a colony of chimpanzees insouthern Cameroon. This discovery, made by an internationalteam headed by Dr. Beatrice Hahn of the Universityof Alabama, may be useful to researchers attemptingto understand why and how HIV causes immune deficiencyin humans (but not in primates) and ultimately guidethe development of new treatments and vaccines.
There are two known genetically distinct AIDS viruses: human immunodeficiency virus-1 (HIV-1) and human immunodeficiency virus-2 (HIV-2). HIV-1 is divided into three major subtypes, or "clades": groups M, N and O. Group M is the clade most widely distributed and associated with the majority of disease globally. Both HIV-1 and HIV-2 are of primate simian immunodeficiency virus (SIV) origin. The origin of HIV-2 has been established to be the sooty mangabey (Cercocebus atys), an Old World monkey of Guinea Bissau, Gabon, and Cameroon. The origin of HIV-1 is found in the "central common" subspecies of chimpanzee.
According to Dr. Hahn, chimpanzees acquired SIV from two smaller primates, the greater spot-nosed monkey (Cercopithecus petaurista) and the red-capped mangabey (Cercocebus torquatus). "The chimpanzee virus is a [mixed form] of ancestors of these other viruses," Dr. Hahn said. "Chimpanzees acquired their infection like humans did, by hunting and consuming naturally infected primates."
Dr. Hahn pointed out the term SIV is a misnomer. "We called it SIV because it's so closely related to HIV, which we discovered first," she said. "However, SIV is not an immunodeficiency virus – it does not cause immune deficiency, or AIDS, in its natural host."
One limitation of the research conducted thus far is the fact that most SIVs are derived from primates studied in captivity. This, Dr. Hahn argued, does not provide information concerning the prevalence, genetic diversity, and geographic distribution in the wild – the information necessary to determine a clear-cut link between HIV and SIV.
The Origin of HIV: Pan troglodytes
Chimpanzees can be divided into two species: the common chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Pan troglodytes can be divided into four subspecies: Pan troglodytes schweinfurthii, also knows as the eastern common chimpanzee; Pan troglodytes troglodytes, or the central common chimpanzee; Pan troglodytes verus , or the western common chimpanzee; and Pan troglodytes vellerosus, or the Nigeria chimpanzee.
Prior to 1999, only three wild-born chimpanzee tested in laboratories had been found to be infected with SIV. Two of the chimpanzees, called GAB1 and GAB2 and caught in Gabon, had viruses that were genetically similar. The third chimpanzee (Noah), confiscated in Antwerp after having been illegally imported from Zaire (now the Democratic Republic of Congo), had a form of SIV that differed from the SIV forms found in GAB1 and GAB2.
In 1999, Dr. Hahn's group analyzed a fourth SIV strain, isolated from frozen samples taken from an African-born chimpanzee (Marilyn) who died of a systemic infection after having given birth to stillborn twins in 1985 while housed at an American primate center.
The analysis revealed that GAB1, GAB2, and Marilyn harbored viruses closely related to each other. All were members of the subspecies P. t. troglodytes. Noah, who harbored the genetically different SIV strain, belonged to the subspecies P. t. schweinfurthii. Analyses also revealed that all HIV-1 strains known to infect humans, including HIV-1 groups M, N, and O, were closely related to the SIV forms found in the P. t. troglodytes, but not in the P. t. schweinfurthii.
Making the Connection: The Study of Chimps in the Wild
SIV prevalence among chimpanzees in captivity is unexpectedly low. In turn, it has been difficult to answer key questions regarding the connection between SIV and HIV. As Dr. Hahn explained, understanding the prevalence, geographic distribution, and genetic diversity of SIV among chimpanzees in the wild is necessary to determine how, why, when, and where SIV was transmitted to humans.
The only way to adequately address these limitations is to evaluate chimpanzees in their natural habitat. However, the evaluation of chimpanzees in the wild presents many challenges. First, they are an endangered species; poaching and lost natural habitat have decimated their numbers. Second, their habitat is remote and fragmented. They live in communities consisting of five to 150 individuals in isolated forest regions. They are also reclusive animals and tend to avoid human contact, except for the rare instances when they have adapted to the presence of human observers.
"All of these factors suggested that collecting blood samples from chimpanzees in the wild was not feasible." In turn, Dr. Hahn's group developed methods to identify SIV and SIV antibodies in chimpanzee urine samples and fecal matter collected from the forest.
Dr. Hahn explained how her study team collects urine from wild chimps. "Trees in the forest contain nests," she said. "The chimps sleep in the nests, in order to avoid being attacked by leopards during the night. We would wake up in the morning before the chimps and stand under the trees with collection baskets. Basically, they do the same thing we do in the morning. We'd capture the urine in the baskets and collect the necessary sample amount. As for feces, we'd collect it off the jungle floor and preserve it for testing."
Dr. Hahn's group tested its methods of specimen collection in Gombe National Park located on the shores of Lake Tanganyika in Tanzania. Gombe is home to three colonies of P. t. schweinfurthii. The arduous process of collecting and analyzing samples from the chimps of Gombe confirmed that SIV specimens found in P. t. schweinfurthii were too genetically different from HIV to be the source of infection. Even more importantly, the work confirmed the value of urine and feces-based testing that could be used in other chimpanzee colonies – including P. t. troglodytes colonies – in other regions of Africa.
The Search in Cameroon
Until recently, urine- and feces-based testing for SIV infection in wild-living chimpanzees from west central Africa – home to a sizeable populations of P. t. troglodytes – has been limited, primarily because of a lack of established field sites with appropriate research infrastructure. Over the past few years, however, Dr. Hahn's group, working with investigators from the University of Montpellier, have collected an analyzed samples collected from wild chimpanzees at different field sites in Cameroon.
Genetic analysis of SIV strains collected from different colonies of chimpanzees indicated that a P. t. troglodytes community near Cameroon's Sangha River had forms of the virus that were most closely related to the most common HIV-1 subtype (clade M). "The genetic similarity was striking," Dr. Hahn said.
HIV-1 clade M has been spread globally, yet the greatest extent of clade M genetic diversity has been reported in Kinshasa, the capital of the Democratic Republic of Congo. In fact, the first human known to be infected with HIV was a man from Kinshasa who had his blood stored in 1959 as part of a medical study – more than two decades before AIDS and HIV were identified. These observations have led to the suggestion that the epidemic began in this geographic region.
While the SIV-infected chimpanzees in southern Cameroon are hundreds of miles away from Kinshasa, an infected bushmeat hunter – exposed to SIV via a bite from a chimpanzee or during the butchering or eating of infected chimpanzee flesh – could have easily traveled to Kinshasa, a city of nearly 7 million people, via the Sangha and Congo Rivers. Over time, with ongoing human transmission of the virus in the human population, the virus may have accumulated the necessary mutations to be become the deadly pathogen it is today.