48-year-old lymph node biopsy reveals the history of the deadly virus.
A biopsy taken from an African woman nearly fifty 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 nearly a century.
Although the AIDS epidemic was not recognized until the 1980s, the HIV virus 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 how best to design a vaccine to fight it.
In 1998, researchers reported the isolation of HIV sequences from a blood sample taken in 1959 from a Bantu male living in what is now Kinshasa, the capital of the Democratic Republic of Congo1. Analysis of that sample suggested that HIV-1 originated sometime between 1915 and 19412.
Now, researchers report in Nature that they have uncovered another sample collected in 1960 from a woman who also lived in Kinshasa3. It took evolutionary biologist Michael Worobey of the University of Arizona in Tucson and his colleagues eight years of searching tissue collections 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 broke 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 methods to sequence DNA and RNA from the samples; another lab at Northwestern University in Chicago, Illinois, also found traces of the HIV genome in the lymph node biopsy.
Using a database of modern HIV-1 sequences and an estimate of the rate at which these sequences change over time, the researchers modelled when the first HIV-1 virus first surfaced. Their results placed that date around 1910, around the time when Kinshasa, then called Léopoldville, was emerging as a center 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 only that predate 1976, 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, France.
A virus ready for its close-up
But it may never be possible to pinpoint exactly how HIV crossed from chimpanzees into humans, Hahn cautions. She and her collaborators previously tracked down the likely source of the virus to chimpanzees living in southeast Cameroon, hundreds of kilometers away from Kinshasa4, and it is tempting to hypothesize that trade routes contributed to HIV's infiltration of the city. But even by 1960, HIV had infected only a few thousand Africans. Tracking down samples from the very earliest victims is unlikely, Hahn notes.
Meanwhile, Worobey plans to continue his search through old tissue collections to find additional samples. In time, he says, it may even be possible to reconstruct the old HIV viruses for further study.
Collecting information about old strains of HIV - even those that disappeared over time - can help teach researchers 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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Ledford, H. Tissue sample confirms HIV has been infecting humans for a century [back by 4pm pls]. Nature (2008). https://doi.org/10.1038/news.2008.1143