Published online 1 October 2008 | Nature | doi:10.1038/news.2008.1143

News

48-year-old lymph node biopsy reveals the history of the deadly virus.

These paraffin-embedded tissue blocks from Kinshasa date from around 1960, and hold fragments of the HIV genome. Dirk Teuwen

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 Léopoldville1 — 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 19412.

Now, researchers report in Nature that they have uncovered another historic sample, collected in 1960 from a woman who also lived in Léopoldville3.

“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.” Michael Worobey

University of Arizona in Tucson

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.

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. Royal Museum for Central Africa

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 Cameroon4, 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."