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The mechanism of resistance of immune cells against HIV is revealed
Last reviewed: 16.10.2021
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Macrophage cells, by releasing an immunodeficiency virus, limit their access to the resources that the virus needs to reproduce. But this strategy has its drawbacks: a hunger virus hides in macrophages, evading immunity detection and antiviral medication attacks.
Do not think that immune cells are completely defenseless against the immunodeficiency virus. Scientists have long known that some cells easily surrender under the onslaught of HIV, while others, on the contrary, stubbornly resist and may not even let the virus go. That is, some of the immune cells have some kind of secret weapon, and understanding the mechanisms of its work would be very useful when creating antiviral drugs.
Some time ago, scientists found the protein SAMHD1, which does not allow HIV to infect macrophages and tree immune cells. In a new article published in the journal Nature Immunology, researchers from the Medical Center of the University of Rochester (USA) describe the mechanism of action of this protein.
The virus, hitting the cell, uses for copying its own DNA cellular resources, that is, deoxyribonucleotides, of which any DNA consists and which are needed by the cell as well as the virus. It turned out that the SAMHD1 protein destroys intracellular deoxyribonucleotides, depriving the virus of the possibility of reproduction. We can say that the virus in macrophages is starving, if we do not mean by hunger to mean energy resources, but building materials necessary for the reproduction of the genome.
The function of macrophages, as is known, is the devouring of infectious agents and infected cells. But in case of eating the virus, there is a danger that it will start to multiply inside the macrophage that has eaten it. Therefore, these immune cells have developed a mechanism that deprives the viruses of resources to reproduce. True, with HIV it does not work as well as we would like. The AIDS virus uses macrophages as a storage chamber: not being able to reproduce in them, it is, however, able to wait out the hard times in the macrophage, evading both the detection by the immune system and the attacks of drugs. Researchers pay attention to the paradox associated with different forms of the HIV virus. HIV-2, unlike HIV-1, can turn off the SAMHD1 protein and multiply easily in macrophages, but it has less virulence than HIV-1, which has to endure and wait for something unknown.
Explaining this paradox, researchers suggest the following. Caught in difficult circumstances, HIV-1 strives to find a way out of them, that is, gets carte blanche for all sorts of mutations: maybe some one will help to cope with the resource constraint. At the same time the virus is enriched by a set of mutations that increase its resistance to drugs, make it even more invisible for the body's defense systems, etc. That is, because of hunger rations, the virus becomes even more ferocious, and it is difficult to say whether the ability of macrophages to starve their prisoners. However, the connection between the increased virulence of the virus and its hunger strikes inside macrophages is still in the field of hypotheses and requires additional experiments to confirm.