Blood tests establish early HIV case.

Exhaustive analyses of a blood sample taken from an African man in 1959 have confirmed the earliest known case of infection with HIV-1, the virus that causes most AIDS cases worldwide.

The finding establishes that HIV was present in people a decade or two earlier than scientists had thought, said Tuofu Zhu of the University of Washington in Seattle, speaking in Chicago this week at the 5th Conference on Retroviruses and Opportunistic Infections.

The man from whom the sample was taken lived in Leopoldville in the Belgian Congo, now Kinshasa in the Democratic Republic of the Congo. His fate is unknown. The man's blood had been preserved as part of a study of blood diseases and was first identified as HIV-positive in 1986, when researchers performed basic immunological tests on it and 1,212 other samples obtained from African patients between 1959 and 1982.

The information collected on the virus at that time was limited by several factors. Scientists then couldn't multiply tiny amounts of viral DNA many thousandfold, as they can today; they lacked knowledge of several HIV-1 subtypes; and they did not have extensive databases of viral DNA.

To find this blood sample's place in the evolution of HIV, Zhu and his colleagues converted viral RNA from the sample into DNA and then made thousands of copies ofthe DNA. The process yielded copies of a few strands of DNA consisting of about 300 nucleotides each. These sequences of HIV-1 found no perfect match among databases of modern HIV-1 sequences.

"The 1959 [viral DNA] sequence was not a mosaic of modern subtypes" of HIV-1, Zhu said at the meeting.

HIV has mutated many times since 1959, and this early sample may provide insights into that process, the researchers suggest in the Feb. 5 Nature. They speculate that all cases of HIV-1 may stem from the introduction of the disease into the African population in the years preceding 1959.

The new analysis shows that the virus in the 1959 sample is closer to a prototype virus than modern HIV-1 is, Zhu says. He and his colleagues found similarities between the old sample and three modern subtypes of HIV-1. Because HIV evolves at a somewhat predictable rate, the researchers could place the sample on a time line leading back to an ancestral HIV-1. They estimate that all subtypes of HIV-1 share a common ancestor "in the late 1940s or early 1950s," Zhu says.

While the finding doesn't reveal the origin of HIV, many scientists suspect that HIV-1 came from chimpanzees and HIV-2 from monkeys called sooty mangabeys. The 1959 sample of HIV-1 is more similar in structure to modern HIV-1 than it is to immunodeficiency viruses in nonhuman primates, an indication that the global spread of HIV-1 occurred only after it had invaded humans, says Simon Wain-Hobson of the Pasteur Institute in Paris in an accompanying commentary.

The finding may prove to have more than historical or academic interest.

"Knowing where something came from and how it ever got into humans in the first place ... would be very important information, because who's to say there aren't more viruses out there that we just don't know how to detect right now," says molecular biologist Michael H. Malim, a Howard Hughes Medical Institute investigator at the University of Pennsylvania Medical School in Philadelphia.