The immune system of some patients is able to effectively resist the human immunodeficiency virus without the help of drugs, American scientists believe. According to the staff of Johns Hopkins University, the existence of this phenomenon is proved by the case history of HIV-infected spouses from the United States they described.
It is known that in some cases, HIV infection does not lead to the destruction of the patient's immune system. Scientists differ in the explanation of this rare phenomenon: according to one version, the ability to resist infection in such patients is due to the characteristics of their immune system, according to another, the slow development of the disease is explained by genetic defects of the immunodeficiency virus itself.
To clarify the mechanisms of extraordinary resistance to HIV infection, scientists turned to the case history of a black couple who had been married for more than twenty years. Ten years ago, a man became infected with HIV through intravenous drug use, and soon the infection was discovered in the woman.
Now the infected man is at a late stage of the disease: he is forced to take large doses of antiretroviral drugs every day. At the same time, his wife’s HIV infection remains asymptomatic: she does not require antiretroviral therapy, and the content of viral particles in her blood remains at a minimal level.
Laboratory studies of virus samples from the spouses' blood clearly confirmed that both of them were infected with the same strain of the virus. The next series of experiments showed that the immune system of patients copes with viral infection differently. The woman's killer cells identified and destroyed the virus in infected cells three times faster than similar cells from the man.
Mutations that reduce the ability of the immunodeficiency virus to reproduce were found in HIV samples taken from both partners. At the same time, weakened virus samples predominated in women, while in men there were significantly fewer of them. According to scientists, the selection of weakened variants of the virus, which was favorable for the patient, did not play a decisive role in the development of the disease and, on the contrary, became possible due to the initially increased activity of her immune system.
According to the authors of the study, their data opens up new opportunities for developers of vaccines and drugs for the treatment of HIV infection. It is quite possible, they believe, that the mechanism of immune defense of individual patients resistant to the virus in the future can be artificially simulated with the help of drugs. The research report was published in
ALL PHOTOS
Every tenth European does not have to fear AIDS. These people are naturally immune to HIV. The answer to the question of why the genetic mutation that provides such protection is more common in Europe than on other continents now seems to have been found by biologists from the University of Liverpool: the fact is that this mutation probably protected against the plague, writes Süddeutsche Zeitung (translation on the website Inopressa.ru).
Therefore, frequent plague epidemics in the Middle Ages ensured the natural selection of people with the mutation. After all, the plague led to inevitable death if a person did not have this mutation, says study leader Christopher Duncan.
It has long been known that a mutation in the CCR5 protein prevents HIV from entering immune cells. British scientists conducted a computer simulation of the spread of the mutation and traced it back to its origins. According to their calculations, the mutation could first appear more than 2,500 years ago, for example, in one of the inhabitants of Mesopotamia, who thereby received immunity from the first documented plague epidemics. After this, during sporadic epidemics, his descendants had the best chance of survival, and thus the mutation spread until the 14th century, when it became protection against the Black Death for one in 20 thousand Europeans.
This major epidemic again gave impetus to the spread of the mutation. In large cities, where the plague always raged most, the CCR5 mutation eventually began to occur in more than 10% of people, British researchers report. They see confirmation of their data primarily in the fact that within Europe the genetic mutation is distributed very differently: about 14% of all Russians and Finns have it, but only 4% of residents of Sardinia.
As shown by the results of historical and computer analysis, the plague raged in Northern Europe much longer than in the Mediterranean.
Scientists have previously suggested a connection between the plague and a mutation in the CCR5 protein. However, no confirmation could be found.
The work of Liverpool researchers was based on a new approach to considering medieval plague epidemics. According to this approach, most of the victims of these epidemics did not die from bubonic plague, caused by the bacterium Yersinia pestis, as was often believed. They rather fell victim to a virus that eventually died out, the British say.
It, like the Ebola virus, caused hemorrhagic fever. This point of view is shared by other researchers who found almost no reference to the bubonic plague in historical descriptions of the Black Death. After all, the CCR5 mutation does not protect against bacteria at all, but it does protect against viruses, the publication writes.
Smallpox, as a possible cause of the spread of the CCR5 mutation, most likely disappears. A year ago, researchers at the University of California, Berkeley, suggested the possibility of such a connection. However, there were severe smallpox epidemics in Europe only from 1700 to 1830.
“But for a mutation to appear in more than 10% of people, it takes at least 600 years of epidemics,” Duncan is convinced.
So, it is possible that the “Black Death,” which raged for so many years, still left something good behind, the publication concludes.
The infectious process caused by a retrovirus proceeds slowly and is accompanied by damage to all body systems, especially the nervous and immune systems. Subsequently, opportunistic infections occur. Also, neoplasms form against the background of the disease. As a result of such pathological changes, the patient's death occurs.
HIV sensitivity to environmental factors
HIV in the external environment is characterized by increased sensitivity to various factors. The virus is destroyed by the components of all chemicals with disinfectant properties. The infectious agent dies when exposed to high temperatures and loses activity when heated to 50 degrees for half an hour. When boiling, HIV resistance is observed for only a few seconds. To ensure the destruction of the pathogen, it is recommended to ensure exposure to higher temperatures, especially when processing reusable medical instruments.
However, the virus is poorly destroyed by solar radiation. Ultraviolet rays obtained artificially have a detrimental effect on it.
If we evaluate the stability of HIV in the external environment when using acidic and alkaline substances, the causative agent of the infectious process loses its activity after a short exposure. Based on this information, we can conclude that with increased pH values of vaginal secretions, the likelihood of infection decreases, but the risk of retrovirus transmission still remains.
The microorganism lives shorter in seawater than the causative agents of other diseases. Cases of infection through sewer and wastewater have not been established, which means that under such conditions the HIV virus in the external environment is not highly active. However, if particles are contained in blood, semen, or vaginal secretions that remain on objects, the pathogenicity of the pathogen can persist for several days.
To what types of external influences is HIV resistant?
Under natural conditions, the virus survives for a long time. As a result of drying blood cells while maintaining a temperature of 23-27 degrees, HIV died only after 3-7 days. In liquids at the same indicators, its activity remains for 15 days. If the temperature is higher and is 36-37 degrees, the viability of the retrovirus remains for 11 days. In frozen blood components, the pathogen can remain intact for years, so donated blood must be subject to the highest level of control.
HIV resistance is observed at low temperatures. According to research results, after blood is frozen, the infectious agent can survive for about 10 years or longer. The HIV virus is resistant to freezing and exposure to low temperatures on sperm. It remains viable in seminal fluid for several months, so sperm donors must also be selected carefully. The content of the virus in the body of insects that consume blood has also been established. However, cases of transmission of infection as a result of a bite have not been recorded.
HIV is resistant to room temperature. These are ideal conditions for its stable existence. At 4 degrees in dried blood, the infectious agent persists for 7 days. As a result of freezing to a temperature of -70 degrees, the virus remains active and can be transmitted to a healthy person. The microorganism survives in used syringes for about 30 days.
The resistance of HIV to environmental factors varies depending on the conditions. In some cases, the virus lives for a long time, therefore, in order to protect yourself from infection, you should adhere to safety measures that will reduce existing risks. Identifying cases of HIV (AIDS) virus persistence in the external environment makes it possible to maximally protect the population from domestic infection with a dangerous disease.
Hello everyone, Olga Ryshkova is with you. Last time we discussed what mutations are, how and where they occur, and whether they are harmful or beneficial for us. Did you know that, thanks to mutations, there are 10% of people among us who will never get HIV infection or AIDS under any circumstances? These are people with innate immunity to HIV. How did they get it?
Why are viruses scary?
Any virus, including HIV, consists of a nucleic acid and a protein shell.
Viruses scare us so much because of mutations and the rapid speed of their reproduction. Frequent mutations allow them to evade the action of the human immune system; it does not have time to synthesize antibodies against new and new mutant forms of viruses, it ceases to recognize them.
New mutated viruses evade the human immune system and this allows them to survive. Due to frequent mutations of the human immunodeficiency virus, it has taken so long to develop a vaccine against HIV. Viruses quickly become resistant to drugs, making treatment more difficult.
How does HIV work?
Once in the human blood, the virus penetrates the cells of the immune system, lymphocytes, and multiplies there. Under the influence of a large number of new viruses, the lymphocyte dies, the viruses enter the bloodstream and penetrate new lymphocytes, destroying more and more of these immune cells.
Over time, immune system cells become fewer and fewer and we say that the immune system weakens, immunity decreases.
A person has a certain number of lymphocytes. If no measures are taken and no treatment is given, HIV will destroy this number of cells in 8-10 years. Then tumors and infectious diseases spread unhindered throughout the body and that’s all. Digressing from the topic, I will say that modern medicine has not learned to destroy HIV inside lymphocytes, but it does this remarkably well when viruses come out of dead cells, preventing HIV from infecting new cells and preserving a person’s immunity.
Hereditary immunity to HIV infection.
And in the course of research, it turned out that 10% of the white population of the planet have congenital, hereditary, genetic immunity to HIV-AIDS. This means that HIV can enter their bodies, but cannot penetrate their immune cells, lymphocytes. Only in cells can viruses multiply, and in the blood plasma, immune cells detect and destroy them. People with hereditary immunity to AIDS will never get HIV infection or AIDS! And all because they inherited such a positive mutation from their ancestors
How so? Where does this heredity come from? After all, we have known HIV for less than four decades, but we know that evolution takes hundreds and thousands of years to consolidate and spread the mutation in people! And why only white people?!
What kind of mutation is this?
People who are immune to HIV infection inherited mutated leukocytes from their ancestors. All other leukocytes contain the CCR5 receptor.
This is where HIV enters the cell. The virus recognizes this receptor and attaches to it. They fit together like a key to a lock.
In the ancestors of people immune to AIDS, the configuration of the CCR5 receptor changed, it became different. This mutated receptor is called CCR5-delta32.
Cells from people with the CCR5-delta32 receptor instead of CCR5 do not accept the virus. When the virus enters the blood and looks for somewhere to attach, it fails. These people are not afraid of AIDS.
This mutation itself has nothing to do with HIV; it was a random mutation. It occurred, took hold and spread when this virus did not exist. People with hereditary immunity to HIV are, one might say, simply lucky to have such a receptor on their lymphocytes.
Why only whites?
This was a side effect of the medieval plague. In the 14th century, the Black Death devastated Europe. She killed 40% of the population. By the time the plague pandemic began, a small proportion of Europeans, approximately 1 in 20,000, already had the mutated CCR5-delta32 receptor.
Both the plague virus and HIV enter the immune system in the same way, using CCR5. The plague epidemic was long, people with the CCR5 receptor died, but those with the CCR5-delta32 receptor survived.
Among survivors, the proportion of mutation carriers increased 2000 times (1:10) and now 10% of Europeans are immune to HIV infection.
A random mutation created a protective wall against the disease and 10% of Europeans may not be afraid of AIDS. Some mutations have a strong effect on disease, others have no effect. This particular mutation occurred by chance and protects people from HIV infection. Look on the map where the CCR5-delta32 mutation is common, allowing people to be immune to HIV infection.
This defense mechanism against infection is the key to anti-HIV drugs. There is a drug called maraviroc, which is already used to treat HIV-infected people. The principle of its action is that it binds to the CCR5 receptor and prevents the virus from attaching to this receptor and entering the cell.
Candidate of Biological Sciences A. LUSHNIKOVA. Based on materials from Scientific American.
The human immunodeficiency virus (HIV) was discovered in 1983 in two laboratories: at the Pasteur Institute in France, under the leadership of Luc Montagnier, and at the National Cancer Institute (USA), Robert Gallo and his colleagues. Now no one has any doubt that HIV causes a terrible disease, the “plague of the twentieth century” - AIDS (this name stands for “acquired immunodeficiency syndrome”). However, over more than a decade of research history, many mysteries have accumulated related to the development of this disease. For example, in some people infected with the immunodeficiency virus, signs of the disease appear after several years or do not appear at all. It turned out that there are people resistant to AIDS. How many such people are there, what characteristics do they have? Isn’t this the key to treating this terrible disease? The published article tries to answer these questions.
This is how the human immunodeficiency virus works. Inside it there is hereditary material - two RNA molecules, on the surface - shell proteins.
In a person with normal immunity, killer cells carrying the CD8 receptor molecule on their surface secrete hormone-like substances, chemokines.
If a person has a normal CCR5 gene, then under the control of this gene a protein is produced in target cells, which, together with another protein (CD4), serves as a “landing platform” for the immunodeficiency virus on the cell surface.
Needle in a haystack
Geneticists have long known about genes for resistance to certain viruses in mice, for example, the leukemia virus. But do similar genes exist in humans, and if so, what is their role in protecting against AIDS?
Stephen O'Brien and Michael Dean and their colleagues from the US National Cancer Institute have been searching for such genes in humans for many years.
In the early 80s, American scientists studied many people who, for one reason or another, could become infected with the immunodeficiency virus. They analyzed thousands of blood samples and discovered a seemingly inexplicable phenomenon: in 10-25% of those examined, the virus is not detected at all, and about 1% of HIV carriers are relatively healthy, their signs of AIDS are either absent or very weakly expressed, and their immune system All right. Is there really some kind of resistance to the virus in some people? And if so, what is it connected with?
Experiments on laboratory mice, rats, guinea pigs and rabbits have shown that resistance to various viral infections is often determined by a whole set of genes. It turned out that a similar mechanism determines resistance to the human immunodeficiency virus.
It is known that many genes are responsible for the production of certain proteins. It often happens that the same gene exists in several altered versions. Such “many-faced” genes are called polymorphic, and their variants can be responsible for the production of different proteins that behave differently in the cell.
By comparing susceptibility to viruses in mice carrying many different sets of genes and in mice with a small number of gene variants, the scientists concluded that the more genetically diverse the animals were, the less often they became infected with the virus. In this case, it can be assumed that in genetically diverse human populations, gene variants that determine resistance to HIV should occur quite often. An analysis of the incidence of AIDS among Americans of various nationalities revealed another feature: Americans of European descent are more resistant, while Africans and Asians have close to zero resistance. How can such differences be explained?
The answer to this question was proposed in the mid-80s by American virologist Jay Levy from the University of California at San Francisco. Levy and his colleagues tried to figure out which cells in the body the virus affects. They found that after the virus infects immune cells, they are easily recognized by another type of immune cell, called killer T cells. Killers destroy cells infected with the virus, preventing further replication of the virus. Killer cells carry a special molecule on their surface - the CD8 receptor. It, like a receiving antenna, “recognizes” signals from cells infected with a virus, and the killer cells destroy them. If all cells carrying the CD8 molecule are removed from the blood, then soon numerous viral particles are found in the body, the virus multiplies rapidly and lymphocytes are destroyed. Isn't this the key to the solution?
In 1995, a group of American scientists led by R. Gallo discovered substances that are produced in killer cells carrying CD8 molecules and suppress the replication of HIV. The protective substances turned out to be hormone-like molecules called chemokines. These are small proteins that attach to receptor molecules on the surface of immune cells when the cells are directed to a site of inflammation or infection. It remained to find the “gate” through which viral particles penetrate into immune cells, that is, to understand which receptors the chemokines interact with.
The Achilles heel of immune cells
Shortly after the discovery of chemokines, Edward Berger, a biochemist at the National Institute of Allergy and Infectious Diseases in Bethesda, USA, discovered a complex protein in the immune cells primarily affected by the virus (called target cells). This protein penetrates cell membranes and promotes the “landing” and fusion of viral particles with the membrane of immune cells. Berger named this protein "fusin", from the English word fusion - fusion. It turned out that fusin is related to chemokine receptor proteins. Does this protein serve as an “entry gate” for immune cells through which the virus penetrates? In this case, interaction with fusin of some other substance will block the access of viral particles to the cell: imagine that a key is inserted into the lock and the viral “loophole” disappears. It would seem that everything fell into place, and the relationship between chemokines - fusin - HIV was no longer in doubt. But is this pattern true for all types of cells infected by the virus?
While molecular biologists were unraveling the complex tangle of events occurring on the surface of cells, geneticists continued to search for genes for resistance to the immunodeficiency virus in humans. American researchers from the National Cancer Institute obtained cultures of blood cells and various tissues from hundreds of patients infected with HIV. DNA was isolated from these cells to search for resistance genes.
To understand how difficult this task is, it is enough to remember that human chromosomes contain about 100 thousand different genes. Testing even a hundredth of these genes would require several years of hard work. The pool of candidate genes narrowed markedly as scientists focused their attention on the cells that the virus first infects—the so-called target cells.
Equation with many unknowns
One of the features of the immunodeficiency virus is that its genes are introduced into the hereditary substance of the infected cell and “lurk” there for a while. While this cell grows and multiplies, viral genes are reproduced along with the cell's own genes. They then enter daughter cells and infect them.
From a variety of people at high risk of contracting HIV, we selected those infected with the virus and those who did not become carriers of HIV, despite constant contact with patients. Among the infected, we identified groups of relatively healthy people and people with rapidly developing signs of AIDS who suffered from concomitant diseases: pneumonia, skin cancer and others. Scientists have studied different options for the interaction of the virus with the human body. The different outcome of this interaction seemed to depend on the set of genes in the individuals studied.
It turned out that people resistant to AIDS have mutant, altered genes for the chemokine receptor - the molecule to which the virus attaches to in order to penetrate the immune cell. In them, contact between the immune cell and the virus is impossible, since there is no “receiving device”.
At the same time, Belgian scientists Michael Simpson and Marc Parmentier isolated the gene for another receptor. It turned out to be a protein that also serves as a receptor for binding HIV on the surface of immune cells. Only the interaction of these two receptor molecules on the surface of the immune cell creates a “landing pad” for the virus.
So, the main “culprits” for infecting cells with the immunodeficiency virus are receptor molecules called CCR5 and CD4. The question arose: what happens to these receptors during resistance to HIV?
In July 1996, American researcher Mary Curington from the Cancer Institute reported that the normal CCR5 receptor gene was found in only 1/5 of the patients she examined. A further search for variants of this gene among two thousand patients yielded surprising results. It turned out that in 3% of people who did not become infected with the virus, despite contacts with patients, the CCR5 receptor gene was altered, mutant. For example, when examining two New York homosexuals - healthy, despite contacts with infected people - it turned out that their cells produced a mutant CCR5 protein that was unable to interact with viral particles. Similar genetic variants were found only in Americans of European descent or people from West Asia, but “protective” genes were not found in Americans of African and East Asian descent.
It also turned out that some patients' resistance to infection is only temporary if they received the "saving" mutation from only one of their parents. Several years after infection, the number of immune cells in the blood of such patients decreased by 5 times, and against this background, complications associated with AIDS developed. Thus, only carriers of two mutant genes were invulnerable to HIV.
But in those with one mutant gene, signs of AIDS still developed more slowly than in carriers of two normal genes, and such patients responded better to treatment.
To be continued
Recently, researchers discovered varieties of extremely aggressive viruses. People infected with such viruses cannot be saved even by the presence of two mutant genes that provide resistance to HIV.
This forces us to continue the search for HIV resistance genes. Recently, American researchers O'Brien and M. Dean and their colleagues discovered a gene that, being present in people in only one copy, delays the development of AIDS for 2-3 years or more. Does this mean that a new weapon has appeared in the fight against the virus that causes AIDS? Most likely, scientists have lifted the curtain on the mysteries of HIV, and this will help doctors in the search for treatments for the “plague of the twentieth century.” Mutant genes have not been found in numerous populations of Afro-Asian Americans, but nevertheless there are small groups healthy people who have been in contact with infected people. This indicates the existence of other genes that protect the immune system from a terrible infection. So far, we can only assume that different human populations have developed their own genetic defense systems. Apparently, for other infectious diseases, including viral hepatitis, There are also genes for resistance to pathogen viruses.Now no geneticist doubts the existence of such genes for the immunodeficiency virus. Research in recent years has given hope of finding a solution to such a seemingly insoluble problem as the fight against AIDS. The future will show who will become the winner in the fight against HIV.
Science to healthcare
HOW TO TREAT AIDS. SEARCHING FOR A STRATEGY
The results of recent research have given thought not only to scientists and practitioners dealing with AIDS problems, but also to pharmacists. Previously, the focus was on combination treatment of infection directed against the virus. Drugs were used that prevent the virus from multiplying in cells: neviparin and atevirdine. This is the so-called group of HIV reverse transcriptase inhibitors, which prevent the hereditary material of the virus from being incorporated into the DNA of immune cells. They are combined with nucleoside analogues such as zidovudine, didanosine and stavudine, which alleviate the course of the disease. However, these drugs are toxic and have side effects on the body, so they cannot be considered optimal. They are increasingly being replaced by more advanced means of influencing HIV.
Recently, it has become possible to prevent viral particles from “landing” on the surface of cells. It is known that this process occurs due to the binding of the viral protein gp120 to cellular receptors. Artificially blocking HIV binding sites using chemokines should protect cells from HIV invasion. To do this, it is necessary to develop special blocking drugs.
Another way is to produce antibodies that will bind to CCR5 receptors, creating a “landing pad.” Such antibodies will prevent these receptors from interacting with the virus, preventing HIV from entering the cells. In addition, fragments of CCR5 molecules can be introduced into the body. In response to this, the immune system will begin to produce antibodies to this protein, which will also block the access of viral particles to it.
The most expensive way to secure viral particles is to introduce new mutant genes into immune cells. As a result, the assembly of the receptor for “landing” the virus on the surface of the “operated” cells will stop, and viral particles will not be able to infect such cells. Such protective therapy appears to be most promising in the treatment of AIDS patients, although it is very expensive.
When treating cancers that accompany AIDS, doctors most often resort to high doses of chemicals and irradiation of tumors, which disrupts hematopoiesis and requires transplantation of healthy bone marrow into patients. What if bone marrow taken from people who are genetically resistant to HIV infection is transplanted into a patient as donor hematopoietic cells? It can be assumed that after such a transplant, the spread of the virus in the patient’s body will be stopped: after all, donor cells are resistant to infection, since they do not have receptors that allow the virus to penetrate the cell membrane. However, this attractive idea is unlikely to be fully translated into practice. The fact is that immunological differences between the patient and the donor, as a rule, lead to rejection of the transplanted tissue, and sometimes to more serious consequences when donor cells attack foreign cells of the recipient, causing their massive death.
Dictionary
Killer T cells- immune cells that destroy virus-infected cells.
Cell receptors- special molecules on the surface that serve as an “identification mark” for viral particles and other cells.
Receptor gene- a gene responsible for the production of the corresponding protein.
Chemokines- hormone-like substances on the surface of immune cells that suppress the reproduction of the virus in the body.
Cell culture- cells that develop outside the body, in a test tube nutrient medium.
Mutant genes- altered genes that are unable to control the production of the desired protein.
Target cells- immune cells that are primarily attacked by the virus.
Figures and facts
Today there are 29 million people infected with the immunodeficiency virus in the world. 1.5 million people have already died from AIDS caused by this infection.
The region most affected by AIDS is Africa. In Europe, the leaders are Spain, Italy, France, and Germany. Since 1997, Russia has joined these countries. In the territory of the former USSR, HIV infection is distributed as follows: 70% - Ukraine, 18.2% - Russia, 5.4% - Belarus, 1.9% - Moldova, 1.3% - Kazakhstan, the rest - less than 0.5%.
By December 1, 1997, about 7,000 people infected with the immunodeficiency virus were officially registered in Russia, mainly through sexual transmission.
There are more than 80 centers for the prevention and control of AIDS in Russia and neighboring countries.
