In the early 1900s, probably near a West African rain-forest, it was thought that a hunter or vendor of bush meat - a wild game that can include primates - acquired the first strain of a simian immunodeficiency virus that scientists consider the ancestor of HIV.
A new study led by researchers from University of Nebraska-Lincoln in the US supported this hypothesis by showing the first in vivo evidence that strains of chimpanzee-carried SIVs can infect human cells.
They include the SIV ancestor of HIV-1 M - the strain responsible for the global HIV pandemic - and another ancestral strain of HIV found only among residents of Cameroon in Africa, researchers said.
They also discovered that the SIV ancestors of two HIV strains not identified in humans also managed to invade human cells after multiple exposures in the lab.
"The question was whether SIV strains that have not been found in humans have the potential to cause another HIV-like infection," said Qingsheng Li from Nebraska Centre for Virology.
"The answer is that, actually, they do. They get replicated at a very high level. It is surprising," said Li.
Researchers came to the conclusions after inoculating mice that were implanted with human tissues and stem cells, which stimulated the growth of other cells essential to the human immune system.
To study why humans have acquired certain HIV strains while avoiding others, researchers injected low doses of the four SIV strains into separate groups of the mice.
They found that the inferred SIV forerunners of HIV-1 M and the Cameroon-specific strain required fewer opportunities to infect the mice than did the two SIV strains whose HIV descendants have not been found in humans.
According to Li, this may stem from the fact that the genetic makeup of the latter two strains differs more from HIV-1 M than does the Cameroon strain, which shares more genes with its pandemic cousin.
"Based on our experiments, we clearly see some differences between the strains. That implies that there might be differences in the likelihood of cross-species transmission when a person is exposed to one strain versus another," said Li.
Researchers also found evidence for the long-suspected notion that SIV strains mutate upon entering cells to overcome human-specific barriers to infection.
Within 14 weeks, the same viral gene in two different SIV strains - including the ancestor of HIV-1 M - regularly underwent mutations at two key positions on that gene.
The experimental approach employed by researchers could help assess the threat posed by additional SIVs and numerous other animal-carried virus.
The findings were published in the Journal of Virology.
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