NEW YORK (GenomeWeb News) – The pandemic, “group M,” strain of HIV-1 was circulating and diversifying in west-central Africa around the turn of the 20th century — decades earlier than previously believed and long before HIV/AIDS was recognized, new genetic research suggests.
In a paper appearing online today in Nature, an international team of researchers used sequencing and comparative genomics to assess an HIV-1 group M strain isolated from a lymph node sample originally taken from a woman in 1960 in what is now Kinshasa, Democratic Republic of the Congo. By comparing it with dozens of other HIV-1 sequences, the team determined that the pandemic strain entered the human population in roughly 1900 — coinciding with a rise in urban centers in west-central Africa.
“From technical and scientific standpoint, it’s a very good and elegant paper,” National Institute of Allergy and Infectious Disease Directory Anthony Fauci told GenomeWeb Daily News. Fauci said the work is “making more precise that date of when HIV started spreading within humans.” Fauci was not involved in the research, although NIAID partially funded the project.
Most of the earliest HIV samples come from the late 1970s and early 1980s when the HIV/AIDS pandemic was first recognized. The oldest documented case of HIV in humans dates back to 1959. That HIV-1 group M virus was isolated and sequenced a decade ago from an African plasma sample collected in what was once Leopoldville in the Belgian Congo (now Kinshasa).
In an attempt to find more pre-AIDS-era viruses, researchers obtained more than 800 paraffin-embedded histopathological blocks from the University of Kinshasa and screened dozens of tissue samples taken between 1958 and 1960 for HIV using RT-PCR. Among them: a wax-embedded lymph node sample, taken from a woman during a tissue biopsy at a hospital in the former Belgian Congo that was HIV-positive.
“Now for the first time we have been able to compare two relatively ancient HIV strains,” lead author Michael Worobey, an ecologist and evolutionary biologist at the University of Arizona, said in a statement. “That helped us to calibrate how quickly the virus evolved and make some really robust inferences about when it crossed into humans, how quickly the epidemic grew from that time, and what factors allowed the virus to enter and become a successful human pathogen.”
The team used an Applied Biosystems 3730 to sequence the virus. But it was far from simple. “The DNA and RNA in these samples is in a really sorry state,” Worobey said. “It’s highly fragmented, so instead of a nice, pearl-strand of DNA or RNA, you have a jumbled mass that’s all jammed together.”
They then compared the virus to dozens of other HIV-1 sequences — including reference sequences from the Los Alamos National Lab HIV sequence database and sequences from three tissue samples taken in Belgium and Canada between 1981 and 1997.
“You can make a model of the time frame it takes for a virus to evolve in a certain way,” Fauci explained. Before this paper, the 1959 sample was being compared against samples taken since about 1976. By starting to fill in this gap, Fauci said, Worobey and his co-workers can now make more precise inferences about when HIV-1 entered the human population.
Based on the family trees they created — along with predicted rates of evolution, the researchers concluded that the new strain, dubbed DRC60, diverged from the 1959 strain between 1884 and 1924. That means that the HIV-1 common ancestor strain first infected humans sometime around the turn of the century.
Around the same time, the large human settlements that would eventually become the cities of Kinshasa (DR Congo), Brazzaville (Congo), Yaoundé (Cameroon), and Bangui (Central African Republic) were established. That underscores the notion that urbanization helped HIV become pandemic in humans.
Previous research suggests that HIV was transmitted from chimpanzees to humans in south-eastern Cameroon, probably via predation. Prior to urbanization, Fauci explained, this type of simian to human transmission was probably occurring relatively frequently in small, dead-end blips. It wasn’t until larger centers started forming that the virus started taking hold and circulating more steadily.
“Whenever you get urbanization, you have a better environment for the spread of infection between humans,” Fauci explained.
In the future, Worobey and his co-workers plan to integrate information about more old HIV-1 strains in order to learn even more about the virus’ history. The team is currently analyzing more samples in an effort to find additional HIV-1 sequences from the early days of HIV infection in humans.
For his part, Fauci said the paper provides historical insights, revealing new details about HIV’s evolution in humans. “It’s a little bit more accurate timetable of how the virus evolved,” he said. Looking both backwards and forwards — to try to predict how the virus will evolve in the future — should provide key HIV insights, he said.