TUCSON, Ariz., Oct. 1 — The urbanization of Africa in the early part of the 20th century may be partly responsible for the spread of HIV, researchers here said.
The suggestion was derived from an analysis of a tissue sample taken in 1960 in what was then Leopoldville, the colonial capital of the Belgian Congo, according to Michael Worobey, D. Phil., of the University of Arizona, and colleagues.
HIV RNA taken from the sample, which had been fixed in paraffin, provided the second oldest viral sequence, next to one from a blood sample — also from Leopoldville — taken in 1959, Dr. Worobey and colleagues wrote in the Oct. 2 issue of Nature.
The key finding is that the two samples — both of HIV-1 Group M — are sufficiently different that their earliest common ancestor must have existed about 50 years previously, the researchers said.
At that time, Leopoldville — and most population centers in central Africa — was small, providing only a small pool in which HIV could spread. But as the cities grew, HIV diversified, the researchers suggested.
“For the first time we have been able to compare two relatively ancient HIV strains,” Dr. Worobey said.
“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,” he said.
Using polymerase chain reaction methods, Dr. Worobey and colleagues scanned 27 Bouin’s-fixed paraffin-embedded blocks of tissue sampled in Leopoldville (now Kinshasa) from 1958 through 1960.
One of the samples contained RNA from HIV-1 Group M, the pathogen responsible for more than 95% of HIV infections worldwide. There are two other HIV-1 groups, as well as HIV-2, but they are less important in the pandemic.
The HIV sample — dubbed DRC60 — was independently sequenced by two different labs and then compared with the other “ancient” sample, known as ZR59.
The researchers found that DRC60 belongs to Group M subtype A — one of 11 subtypes — while ZR59 belongs to subtype D.
Analysis showed that the sequences differed by about 12%, greater than 99.2% of within-subtype comparisons, the researchers said. For instance, the uncorrected pairwise distance between DCR60 and ZR59 in their overlapping env region was 11.7%.
“Because each subtype represents several decades of independent evolution in the human population,” the researchers said, “the extensive divergence between DRC60 and ZR59 indicates that the HIV-1 M group founder virus began to diversify in the human population (and that HIV-1 probably entered Kinshasa) decades before 1960.”
A statistical analysis suggested that Group M had relatively slow growth in the first half of the twentieth century — a time when colonial centers such as Leopoldville had been established and were beginning to grow, the researchers said.
The notion that HIV was spreading among humans for several decades before AIDS was first recognized “should not be surprising,” said Paul Sharp, Ph.D., of the University of Edinburgh, and Beatrice Hahn, M.D., of the University of Alabama at Birmingham.
If the epidemic grew exponentially, the curve would suggest that there were only a few thousand HIV-infected individuals by 1960, all in central Africa, they said in an accompanying News & Views article.
And because AIDS has a variety of symptoms and often a long period without any symptoms at all, “it is easy to imagine how the nascent epidemic went unrecognized,” they said.
Nevertheless, the work by Dr. Worobey and colleagues allows “a remarkably detailed picture of the time and place of origin of HIV-1 group M viruses and their early diversification, and thus of the prehistory of the AIDS pandemic.”
Drs. Sharp and Hahn, with colleagues, reported in 2006 that the closest animal match to HIV-1 Group M — a simian immunodeficiency virus (SIV) — was found in chimpanzees in Cameroon, about 440 miles (700 km) from Kinshasa.
The simplest explanation of how SIV jumped to humans would be through exposure to the blood of infected chimps, they argued. But then why did the pandemic start in Leopoldville and why not until the 20th century?
“The answer may be that, for an AIDS epidemic to get kick-started, HIV needs to be seeded in a large population center,” they said. “But cities of significant size did not exist in central Africa before 1900.”
Indeed, Dr. Worobey and colleagues said, before 1910 there was not a single population center of more than 10,000 people anywhere in Central Africa.
“I think the picture that has emerged here — where changes the human population experienced may have opened the door to the spread of HIV — is a good reminder that we can make changes now that could help reverse the epidemic,” Dr. Worobey said.
The researchers said that archived tissue samples in African hospitals form “a vast source of clinical material” that could “yield important insights into the pathogenesis, virulence, and evolution of pandemic AIDS viruses.”
The study was supported by the National Institute of Allergy and Infectious Diseases and the David and Lucile Packard Foundation. The researchers did not report any conflicts.
Primary source: Nature
Worobey M, et al “Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960″ Nature 2008; 455: 661-665.
Additional source: Nature
Sharp PM, Hahn BH “Prehistory of HIV-1″ Nature 2008; 455: 605-606.