How HIV appeared
On June 5, 1981, experts from the US Centers for Disease Control and Prevention (CDC)
Thus began a new epidemic, which at first few people paid attention to, but which soon swept the entire globe: after a few years, tens of millions of people fell ill.
HIV was transmitted to us directly from monkeys(unlike, for example, coronavirus, it does not have an intermediate “host”). The SIV virus (Simian immunodeficiency virus) is still spreading among monkeys, but it does not cause pathologies in most of them.
They can artificially, in laboratory conditions,Infect only one species of monkey (rhesus macaques), and in them SIV causes the same abnormalities in the immune system as in humans. But the virus does not affect the life activity of other species of monkeys, such as mangabeys.
At first, scientists thought that these primates possessedsuch a good immune system that they simply do not get infected with HIV. In fact - and this was an important breakthrough in virology - the Mangobey simply do not have an immune response to this virus.
What methods are used to treat HIV
For 2017, about 30 drugs are used in the treatment of HIV infection, which makes it possible to select the optimal therapy for each patient.
To date, no method has been developedcure for HIV infection, which could completely eliminate the human immunodeficiency virus from the body. This occurs due to the characteristics of the virus itself, which forms reservoirs (sanctuaries) in the human body.
Previously, to indicate the treatment regimens usedHIV was referred to as HAART or highly active antiretroviral therapy. Currently, this definition has lost its relevance, since, due to the development of medical science, any antiretroviral therapy involves a complex of medicinal components (from 2 to 4 in one treatment regimen), is highly active and the abbreviation ART or ART is more often used.
Modern ART allows long-termcontrol HIV infection indefinitely and exclude the onset of AIDS in the patient, subject to its virological effectiveness and compliance with regular medications (adherence to treatment), allowing an HIV-infected person to live a full life indefinitely.
With the use of treatment and provided that the effectiveness of the drugs is maintained, a person's life expectancy is not limited by HIV, but only by natural aging processes.
Currently the first person to recoverfrom HIV, is considered the American Timothy Ray Brown, nicknamed the "Berlin Patient". However, many researchers believe that the method of treatment, thanks to which Brown was able to eliminate the virus from the body, cannot be considered a panacea for HIV.
March 5, 2019At an international conference in Seattle on retroviruses and opportunistic infections, scientists reported two encouraging results: two more people, the "London patient" and the "Düsseldorf patient", are in remission after a bone marrow transplant. Doctors deliberately use the word "remission", meaning that both people have no signs of HIV, but it is too early to talk about a complete cure.
Like Brown, the "London patient" was sickcancer, but not leukemia, but Hodgkin's lymphoma. He also needed a bone marrow transplant, and a donor was found for him with the same mutation as for Brown. The difference is that the "London patient" was not previously given courses of radiation and chemotherapy, and a bone marrow transplant was done only once.
The third person, the "Düsseldorf patient", alsohad lymphoma, did not receive radiation therapy, and he received bone marrow transplants once, not twice. For 3.5 months after that, despite the discontinuation of antiviral therapy, the patient remains healthy.
Mutation for HIV resistance
MutationCCR5Δ32makes human T cells resistant to infectionHIV. A transplant of blood cells from a donor with a mutation can save the patient from infection - as was the case with the “Berlin patient”, and then with the “London” and, possibly, the “Dusseldorf” patient.
However, in Europe, carriers of this mutation are onlya few percent of the population and it is quite difficult to find a fully compatible donor. And in some countries, for example, in China, where there are practically no carriers, this turns into an impossible task at all.
Modern genome editing technologiesmake it possible to do without a donor. To do this, you need to take the patient’s own cells and introduce the necessary mutation into them or simply destroy the corresponding gene. This is the first time a company has decided to do this.Sangamo Therapeutics: They reported their first clinical trial in 2014.
For genome editing, researchersused zinc finger nuclease. This is an enzyme that contains sections—actually, “fingers”—that can recognize a specific sequence in DNA, and a section that can introduce a break in the DNA strand next to this sequence.
Blood T cells were taken from 12 patients and added totheir genome is altered and returned to the body. At this point, the subjects were no longer treated for HIV. The edited cells took root in the patients' bodies, but they could not make them completely resistant - all but one had to return to antiretroviral therapy. After that, Sangamo Therapeutics stopped its HIV drug development and switched to fighting other diseases.
Since then, "zinc fingers" have been replaced bynew genome editing technology - CRISPR / Cas9 system. It differs favorably in that it is not proteins that are responsible for recognizing DNA in it, but an RNA molecule, which is faster to synthesize and easier to make specific to a particular sequence.
HIV —record holder for mutations
The immunodeficiency virus has several strategiessurvival. First, the duration of the course of the disease: the virus needs it in order for a person to have time to transmit the infection to other people. Secondly, the virus benefits from the very way the pathogen enters the body, especially the sexual route of transmission.
It has been proven that women are 3 times more likely to become infected from an infected partner. This is due to the structure of the genitals and the large amount of seminal fluid in men.
The third survival strategy of the immunodeficiency virus- its entry into the human immune system. And finally, another "invention" of HIV in the struggle for survival - mutations, which for him are a guarantee that the immune response of the infected will not be able to hit him. It takes time for an immune response to occur. For example, if a person gets sick with the flu, then it takes about a week for the immune system to activate and destroy the virus. But HIV mutates so quickly that the immunity that occurs in an infected person will simply not recognize the virus in a week.
HIV vaccine
At the beginning of December 2020, the head of RospotrebnadzorAnna Popova spoke about the “high degree of readiness” of the Russian HIV vaccine. Its developers confirmed to journalists that in the first phase of clinical trials, 100 percent of volunteers developed antibodies to the virus. By the way, an article with their report was published back in 2016.
The vaccine that Popova spoke about (“CombiHIVvac”) is being developed by the Novosibirsk Vector Center.
According to the mechanism of action, "CombiHIVvac" refers topolyepitope vaccines. This is an artificial virus-like particle, that is, a protein “box”, inside of which there is circular DNA with some viral genes.
Such a design should arouse suspicion right away.in two branches of immunity. B cells should react to surface proteins and begin to produce antibodies specific to the virus. And DNA must get inside human cells and make them also collect several surface proteins of the virus - and introduce them to T cells.
But the only thing we know about the CombiHIVvac's performance today is the results of the first phase of its tests, published in 2016 in the journal Bioorganic Chemistry.
Antibodies from the blood of volunteers were neutralizeddifferent subtypes of the virus with different efficacy. Six months after vaccination, option A / 392 could “neutralize” antibodies in 71 percent of the participants, and option B / PV04 - only 29 percent. And a year after the injections, none of the subjects had these antibodies in their blood.
How HIV is studied today
At the end of May 2021, Austrian scientists found outthe key role of the molecule of inositol hexakisphosphate (IP6) in the life cycle of Rous sarcoma (RSV), which belongs to the same family of RNA viruses as HIV.
The team studied the mechanism of action of the IP6 molecule, which is used in the assembly of particles of the Rous sarcoma virus, and identified its crucial role in the life cycle of RSV and similar retroviruses.
The molecule itself substitutes a compound of phosphoric acid and inositol alcohol. It is noted that it is found in large quantities in human cells.
The molecule promoted the connection ashexamers and pentamers, constituents of the capsid, into structures of six units. At the same time, with a lack of IP6, the protein membranes were combined in a chaotic manner, which prevented the appearance of viable virus particles.
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