AIDS resistance
6 Facts about the Genetic Mutation that Protects People
from contracting HIV infection
Svetlana Borinskaya, Post-scienceAIDS is called the "plague of the XX century".
The causative agent of the disease of progressive immunodeficiency syndrome was discovered in the 1980s. It turned out to be a virus previously unknown and got to people, apparently not so long ago from the wild. The epidemic spread all over the world, and huge efforts were spent in search of treatment and methods to prevent infection.
1. The cause of HIV resistancePeople who were infected with this new virus were examined and monitored in order not to miss the onset of the disease and to identify their partners who could also be infected.
When examining several hundred people, it was found that some partners of HIV-infected people do not get infected with this virus. It turned out that the cause of resistance to infection is a mutation in one of the human genes. This gene encodes a protein that serves as a "landing pad" for the immunodeficiency virus. By binding to this protein, the virus enters the cell. If there is no protein, then the virus has nothing to "catch on", and it does not penetrate into the cell, and thus the infection does not develop.
2. Defective genesThere are about 1% of people resistant to HIV infection in European populations.
These are people who have both copies of the gene encoding the protein that serves as a "landing pad" for the virus. A person receives one copy of each gene from his mother, the second from his father. If only one of these two copies is defective, then the person will be more resistant to infection, but not much. The probability of being infected by contact with the virus will be only 10-13% lower compared to those who have both copies of the gene normal. Carriers of such a defective gene, if they are infected, acquired immunodeficiency syndrome will develop for several years longer, and the mortality rate from this disease will be lower.
3. The spread of mutationThe discovery of this mutation allowed the development of an AIDS vaccine to begin.
The vaccine aims to block this protein and make the cell inaccessible to the virus. The highest frequency of mutation that spoils the gene and the protein receptor that binds to the immunodeficiency virus is in Northwestern Europe: Finns, Estonians and northern Russians. There, the number of carriers of this mutation reaches 25%. Of these, only a small part has a defect in both copies of the gene, and the rest have one defective and one normal copy.
Carriers of one defective copy are not resistant to infection, they still get infected with this virus when they encounter it. But when infected, the infection develops more slowly in them, because they still have fewer receptors, the virus multiplies more slowly. When the mutation was discovered and it turned out that it occurs mainly in the peoples of Europe, and in other peoples this mutation is practically absent, the researchers suggested that in Europe it could protect people from some other infection, for example, from the plague that raged in Europe in the XIV century. This assumption has not been confirmed, and it is still unknown what reason caused the spread of this mutation.
4. Possible cause of mutationSome clarity arose during the study of bone remains in burials in Europe.
It turned out that already three thousand years ago, the frequency of this mutation in the European population of that time was close to the modern one. So something happened in Europe that led to an increase in the frequency of mutation. In addition to resistance to infections, these could be random events, for example, a change in population size, which sometimes leads to the growth of completely neutral gene variants. But this mutation, apparently, was still something useful and contributed to selection.
There are peoples who came to Europe relatively recently. These are Jews who settled from their Middle Eastern ancestral homeland two thousand years ago, and Gypsies who left India about a thousand years ago and moved to Europe. Jews and Gypsies had an influx of genes from their European neighbors. Jews have less, according to some estimates up to 20%, Gypsies had a greater influx of genes. But they have the same frequencies of this mutation as Europeans. This suggests that when they came to Europe, they were faced with the same factor that affected people who had lived in Europe for a long time, and their mutation frequency increased. But with what factor, it is still unknown.
5. The effect of mutation on HIV-infectedThis mutation is being studied quite intensively even now, but it is not yet known how it affects the features of the immune system.
And it is necessary to find out what it protects a person from now or protected in the distant past. The research carried out by geneticists helps to develop vaccines to prevent infection with the human immunodeficiency virus.
We investigated the effect of this mutation on the survival of HIV-infected people. The older generation remembers the tragedy that occurred in the late 1980s in the Soviet Union, when more than two hundred children were infected in hospitals in Elista and Rostov-on-Don. The doctors who monitored these children and treated them took blood samples all the time in order to determine the viral load. Mutations (in DNA isolated from this blood) protecting against HIV infection were analyzed.
6. Protective effect of mutationIt turned out that children who are carriers of this very mutation in the gene of the receptor with which the immunodeficiency virus binds have a lower mortality rate from HIV.
And the HIV-infected group itself had a lower frequency of this mutation than the control group of people of the same origin living in the same region. This indicates the protective effect of the mutation.
However, the difference is small. In order to establish whether the protective effect is reliable, a small group of examined is not enough, and it is necessary to compare the results of dozens of studies and use statistical methods that show that in most studies the frequency of mutations in HIV-infected people is lower than in control groups of the same origin. These differences are not very large and, perhaps, are not very significant for epidemiology. The peoples with the highest frequency of this mutation (25%) are slightly better protected than the population of Africa or Asia, where there is no such mutation. But the differences at the level of the population as a whole are relatively small – a decrease in infection rate by only 5% or 10%.
Therefore, the presence of this mutation in relation to the development of the AIDS epidemic has very little effect on the population level. But, of course, it is significant for an individual. And carrying out a genetic analysis for the presence of such a mutation may be important for people in those professions who have an increased risk of infection, for example, for doctors or those who work with blood. If a person is genetically protected from infection, it will probably be easier and calmer for him to work, but this does not negate the precautions that need to be taken.
About the author:
Svetlana Borinskaya – Doctor of Biological Sciences, Leading Researcher
Genome Analysis Laboratories of the N. I. Vavilov Institute of General Genetics of the Russian Academy of Sciences.
Portal "Eternal youth" http://vechnayamolodost.ru29.08.2014