Many fundamental questions about HIV infection, the world's leading infectious killer, remain unanswered. There is considerable variation in susceptibility to and progression of the infection, which kills approximately 1.8 million people annually. However, it is clear that the genetic makeup of the host plays an important role in both susceptibility and resistance to the disease.

In humans, the CCR5 gene encodes the CCR5 protein on the surface of white blood cells, which acts as a receptor for chemokines. The receptor for CCL5 chemokine proteins helps direct immune cells to inflamed areas, but unfortunately it also helps HIV bind to and enter the cell.

"For HIV, however, they are like door handles to grab hold of and enter the cell. In the case of the protective gene variant, this gene has a 32-letter deletion. This gene is essentially broken in these people, so there is no door handle. This virus cannot enter the white blood cells of these people," Professor Mait Metspalu, the director of the institute of genomics at the University of Tartu, explained at the "Vikerhommik" morning show.

Humans naturally have copies of every gene. In other words, both copies must be broken for strong protection. "Around 1.3 percent of us have defects in both gene variants in this locus, which protect against HIV. About 23 percent have one variant defective," Metspalu went on to say. Looking at Estonia as a whole, the frequency varies between 11 and 13 percent, according to the data from the gene repository.

However, he said, it is also important to bear in mind that only one type of HIV uses the chemokine receptor as its only door lining. Others may find other ways to infect cells.

Metspalu said that the defective gene is not unique to Estonian people. Its prevalence is also very high in the rest of northern Europe. "It starts to fall as you go south. It's already about 5 percent in the Mediterranean and even less in the south. It's a very intriguing evolutionary biology question; why is that?"

Based on current research, Metspalu said the gene variant is relatively recent. "Its frequency started to increase significantly only a few thousand years ago. It is not entirely clear what the mechanism behind this is. It is possible that this gene variant also gave protection against viral diseases in the past. It was probably the smallpox virus, which is rather similar to HIV," he said.

Because certain types of the smallpox virus killed a large proportion of those infected, people with the protective variant would have had many more children. This would have increased its prevalence in the population as a whole.

But there is no good without a bad. "On the other hand, this healthy gene seems to offer protection against the virus that causes tick-borne encephalitis. So all the others have better protection against encephalitis," Metspalu said.

Estonian Biobank comprises over 200,000 individuals, or 20 percent of Estonia's adult population, providing researchers with a unique dataset to analyze the impact of DNA on health, diseases and treatment outcomes.

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