Quantcast

Researchers Track The Origins Of HIV Through Genetic Variants

December 19, 2012

April Flowers for redOrbit.com – Your Universe Online

A new study, led by Alfred Roca of the College of Agricultural, Consumer and Environmental Sciences (ACES) at the University of Illinois, reveals that human immunodeficiency virus (HIV) may have affected humans for much longer than is currently believed. Roca, an assistant professor, believes the genomes of an isolates West African population provides important clues about the evolution of the HIV virus.

HIV is thought to have originated from a retrovirus called Simian Immunodeficiency virus (SIV) found in chimpanzees in central Africa.

“If you look at the diversity present across SIV in chimpanzees, it suggests that they have had it for tens of thousands of years,” Roca said.

Ninety percent of human infections come from the HIV-1 Type M, which is believed to have crossed the species barrier into human populations sometime between 1884 and 1924. It may have crossed much earlier and many times, according to Roca, selecting for genetic resistance while remaining undetected in isolated rural populations.

“Some of the scientific literature suggests that the persistence of HIV in humans required population densities typical of the larger cities that appeared in West Central Africa during the colonial era,” he said.

Before modern medicine and vaccinations, diseases such as smallpox killed large numbers of people. Roca and his team suggest that people with suppressed immune systems from HIV may have succumbed to the infectious disease first, preventing the immunodeficiency virus from spreading very far.

If, as Roca suggests, the HIV virus has crossed the species barrier many times, the possibility exists that selection favored protective genetic variants in the affected populations. The team examined Biaka genomes for evidence of this selection.

The Biaka were chosen because they are a human population living in forests inside the range of the chimp subspecies thought to be responsible for the current HIV pandemic. Genomes of four populations living outside the chimpanzees’ range were compared with the Biaka, whose genes were made available through the Human Genome Diversity Project.

The project collected biological samples from 52 different population groups across the world, then genotyped these diverse human populations for single nucleotide polymorphisms (SNPs or “snips”), or genetic variations, at approximately 650,000 locations across the genome.

Using cell lines made in the 1980s from people who had AIDS or were thought to be at risk, previous research had identified 26 genomic locations as possibly being involved in resistance to HIV. Kai Zhou, a graduate student in Roca’s lab, examined these locations, running all 10 possible pairwise comparisons for the five distinct human populations, looking for selection signatures.

Within the affected population, selection for a genetic trait tends to reduce diversity in the surrounding genomic region, while increasing the differences between populations. The team examined the genomic regions that contain genes known to have a protective effect against HIV trying to determine if there was any overlap with the selection signatures. Overlap was found in eight of the comparisons, seven of which involved the Biaka.

The team identified four genes in these areas of overlap that code for proteins that either affect the ability of HIV to infect the host cell or the disease progression. For several genes, the team found that SNPs associated with protection against HIV-1 were common among the Biaka.

The results of this study should not be considered definitive, Roca cautions, as it is not possible to rule out false positives.

“You may detect a signature of selection, but it doesn’t necessarily mean that selection has caused it. It’s just a good sign that selection may have occurred,” he said. He also warned that the signature selection may span several genes, of which only one is actually protective.

Roca does say the results are intriguing, suggesting this line of research is well worth pursuing.

“If additional studies confirm that these genes have undergone selection and that human populations in the region have some genetic resistance to HIV-1, one could try to find additional genes in the population that may also be protective against HIV but have not yet been identified,” he said.

“The mechanism by which these genes work could be determined,” he continued. “It could open up a new line of research for fighting retroviruses.”

The results of this study were recently published online in the journal BMC Evolutionary Biology.


Source: April Flowers for redOrbit.com - Your Universe Online



comments powered by Disqus