This photo shows Kinshasa around 1885, shortly after its founding.
The growth of Kinshasa and other cities in the region
may have been crucial to the emergence of HIV/AIDS.
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Tissue sample suggests HIV has been infecting humans for a century
Tissue sample suggests HIV has been infecting humans for a century
48-year-old lymph node biopsy reveals the history of the deadly virus.
Heidi Ledford (nature.com, 1/10/2008)
A biopsy taken from an African woman nearly 50 years ago contains traces of the HIV genome, researchers have found. Analysis of sequences from the newly discovered sample suggests that the virus has been plaguing humans for almost a century.
Although AIDS was not recognized until the 1980s, HIV was infecting humans well before then. Researchers hope that by studying the origin and evolution of HIV, they can learn more about how the virus made the leap from chimpanzees to humans, and work out how best to design a vaccine to fight it.
In 1998, researchers reported the isolation of HIV-1 sequences from a blood sample taken in 1959 from a Bantu male living in Léopoldville — now Kinshasa, the capital of the Democratic Republic of the Congo. Analysis of that sample and others suggested that HIV-1 originates from sometime between 1915 and 1941.
Now, researchers report in Nature that they have uncovered another historic sample, collected in 1960 from a woman who also lived in Léopoldville.
It took evolutionary biologist Michael Worobey of the University of Arizona in Tucson and his colleagues eight years of searching for suitable tissue collections originating in Africa before they tracked down the 1960 lymph node biopsy at the University of Kinshasa.
Drenched in glue
The samples had all been treated with harsh chemicals, embedded in paraffin wax and left at room temperature for decades. The acidic chemicals had broken the genome up into small fragments. Formalin, a chemical used to prepare samples for microscopy, had crosslinked nucleic acids with protein. "It's as if you had a nice pearl necklace of DNA and RNA and protein and you clumped it together, drenched it in glue and then dried it out," says Worobey.
The team worked out a combination of methods that would allow them to sequence DNA and RNA from the samples; another lab at Northwestern University in Chicago, Illinois, confirmed the results, also finding traces of the HIV-1 genome in the lymph node biopsy.
Using a database of HIV-1 sequences and an estimate of the rate at which these sequences change over time, the researchers modelled when HIV-1 first surfaced. Their results showed that the most likely date for HIV's emergence was about 1908, when Léopoldville was emerging as a centre for trade.
Although that date will not surprise most HIV researchers, the new data should help persuade those who were unconvinced by the 1959 sample, says Beatrice Hahn, an HIV researcher at the University of Alabama at Birmingham.The sequences of the 1959 and 1960 samples - the earliest that have ever been found - show a difference of about 12%. "This shows very clearly that there was tremendous variation even then," says Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris.
A virus ready for its close-up
However, it may never be possible to pinpoint exactly how HIV crossed from chimpanzees into humans, Hahn cautions. She and her collaborators previously tracked the likely source of HIV-1 to chimpanzees living in southeast Cameroon, hundreds of kilometres from Kinshasa, and it is tempting to hypothesize that trade routes contributed to the virus's infiltration of the city. But even by 1960, HIV-1 had infected only a few thousand Africans. It is unlikely that it will be possible to track down samples from the very earliest victims, Hahn notes.
Meanwhile, Worobey plans to continue his search through old tissue collections in the hope of finding additional samples. In time, he says, it may even be possible to reconstruct the historic HIV viruses for further study.
Collecting information about old strains of HIV — even those that disappeared over time — can help researchers learn how successful strains broke through, says Wain-Hobson. "For every star in Hollywood there are fifty starlets," he says. "We would love to know what it was that caused this strain to move out of starlet phase and to the big time."
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HIV/AIDS Emerged as Early as 1880s
Amitabh Avasthi (National Geographic News,1/10/2008)
The AIDS pandemic in humans originated at least three decades earlier than previously thought, and it may have been triggered by rapid urbanization in west-central Africa during the early 20th century, according to an international team of researchers.
A better understanding of the conditions that helped fuel the pandemic could be key in controlling the disease and preventing future outbreaks of other emerging viruses.
"Rapid urbanization was the turning point that allowed the pandemic to start," said Michael Worobey, an evolutionary biologist at the University of Arizona, Tucson, and lead author of the study.
"We as human beings made some changes that took a virus that could not exist on its own and turned it into a successful epidemic," he added.
Birth of AIDS
Until now it was thought that HIV-1 Group M, the strain of HIV that causes the most infections worldwide, originated in 1930 in Cameroon.
Epidemic levels of AIDS and HIV-1 infections started appearing in Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo), around 1960.
Findings from the new study, however, suggest that the virus most likely started circulating among humans in sub-Saharan Africa sometime between 1884 and 1924.
Worobey and his colleagues made the discovery while analyzing tissue samples collected between 1958 and 1960 from Kinshasa. One of them, acquired in 1960, contained bits of HIV-1 RNA, the virus's genetic material.
The researchers compared the 1960 virus with the oldest known HIV-1 strain, which was obtained in 1959 and evolved independently of the 1960 variant. They found that the 1960 version was significantly different.
Next the researchers constructed an evolutionary family tree of the HIV-1 virus, made up of both the 1959 and 1960 strains along with more than a hundred modern viral sequences.
Using a mathematical model, Worobey and his colleagues discovered that the 1960 strain must have been evolving for at least 40 years to account for the number of differences from the 1959 strain.
The model also traced the most recent common ancestor of both strains to 1908.
The team's findings appear today in the journal Nature.
"This confirms that this was a virus that was lurking around for many decades before it exploded into the human population to become a noticeable pandemic, as opposed to something that started in the '70s or '80s," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), in Maryland.
NIAID funded the study along with the National Institutes of Health.
"It solidifies our understanding of the timetable of how this virus emerged from the chimpanzees to establish itself as a human infection," Fauci added.
"[HIV-1] flew below the radar level for decades until social conditions such as the end of colonization, migration of people to cities, increase in prostitution, and promiscuous sexual activity made it much easier for the disease to explode into a pandemic," Fauci explained.
More Mutations
Robert Garry is a microbiologist at New Orleans's Tulane University who was not involved with the study.
In the late 1980s, Garry was the first scientist to examine tissues samples taken from the U.S.'s first confirmed AIDS patient, who died in 1969.
"This study is very important, and what they are finding here is when the human virus started circulating in people," he said. "We still don't know when exactly the virus jumped from chimpanzees to humans, but it may be pushed back even further with this study.
"There will be other emerging viruses in the future, and what we learn about the conditions that help viruses spread, be it social changes or changes within the virus itself, will make us better prepared for other epidemics," he said.
Garry also argues that, though the rapid growth of cities in west-central Africa may have sparked the spread of infections, the virus itself underwent some sort of genetic change to facilitate transmission.
"We have to figure out what that change was," he cautioned.
Study traces AIDS virus origin to 100 years ago
By MALCOLM RITTER
AP Science Writer, October 1, 2008
NEW YORK (AP) - The AIDS virus has been circulating among people for about 100 years, decades longer than scientists had thought, a new study suggests. Genetic analysis pushes the estimated origin of HIV back to between 1884 and 1924, with a more focused estimate at 1908.
Previously, scientists had estimated the origin at around 1930. AIDS wasn't recognized formally until 1981 when it got the attention of public health officials in the United States.
The new result is "not a monumental shift, but it means the virus was circulating under our radar even longer than we knew," says Michael Worobey of the University of Arizona, an author of the new work.
The results appear in Thursday's issue of the journal Nature. Researchers note that the newly calculated dates fall during the rise of cities in Africa, and they suggest urban development may have promoted HIV's initial establishment and early spread.
Scientists say HIV descended from a chimpanzee virus that jumped to humans in Africa, probably when people butchered chimps. Many individuals were probably infected that way, but so few other people caught the virus that it failed to get a lasting foothold, researchers say.
But the growth of African cities may have changed that by putting lots of people close together and promoting prostitution, Worobey suggested. "Cities are kind of ideal for a virus like HIV," providing more chances for infected people to pass the virus to others, he said.
Perhaps a person infected with the AIDS virus in a rural area went to what is now Kinshasa, Congo, "and now you've got the spark arriving in the tinderbox," Worobey said.
Key to the new work was the discovery of an HIV sample that had been taken from a woman in Kinshasa in 1960. It was only the second such sample to be found from before 1976; the other was from 1959, also from Kinshasa.
Researchers took advantage of the fact that HIV mutates rapidly. So two strains from a common ancestor quickly become less and less alike in their genetic material over time. That allows scientists to "run the clock backward" by calculating how long it would take for various strains to become as different as they are observed to be. That would indicate when they both sprang from their most recent common ancestor.
The new work used genetic data from the two old HIV samples plus more than 100 modern samples to create a family tree going back to these samples' last common ancestor. Researchers got various answers under various approaches for when that ancestor virus appeared, but the 1884-to-1924 bracket is probably the most reliable, Worobey said.
The new work is "clearly an improvement" over the previous estimate of around 1930, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. His institute helped pay for the work.
Fauci described the advance as "a fine-tuning."
Experts say it's no surprise that HIV circulated in humans for about 70 years before being recognized. An infection usually takes years to produce obvious symptoms, a lag that can mask the role of the virus, and it would have infected relatively few Africans early in its spread, they said.
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