June 1, 2006

Making the Link: Chimps Believed Source of HIV

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.

Background

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.

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