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The mechanism of immune cell resistance against HIV has been uncovered
Last reviewed: 01.07.2025
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Macrophage cells, having let the immunodeficiency virus into themselves, limit its access to the resources that the virus needs to reproduce. But this strategy has its drawbacks: the starving virus hides in macrophages, evading detection by the immune system and attacks by antiviral drugs.
It is not worth thinking that immune cells are absolutely defenseless against the immunodeficiency virus. Scientists have long known that some cells easily give in to the onslaught of HIV, while others, on the contrary, stubbornly resist and may not let the virus in at all. That is, some immune cells have some kind of secret weapon, and understanding the mechanisms of its work would be very useful in creating antiviral drugs.
Some time ago, scientists discovered the protein SAMHD1, which prevents HIV from infecting macrophages and dendritic immune cells. In a new article published in the journal Nature Immunology, researchers from the University of Rochester Medical Center (USA) describe the mechanism of action of this protein.
Once inside the cell, the virus uses cellular resources to copy its own DNA, that is, deoxyribonucleotides, which any DNA consists of and which the cell needs just as much as the virus. It turned out that the SAMHD1 protein destroys intracellular deoxyribonucleotides, depriving the virus of the ability to reproduce. We can say that the virus in macrophages is starving, if by starvation we mean not energy resources, but building materials necessary for reproducing the genome.
The function of macrophages is known to be to devour infectious agents and infected cells. But if a virus is eaten, there is a danger that it will start to multiply inside the macrophage that ate it. Therefore, these immune cells have developed a mechanism that deprives viruses of resources for multiplication. However, this does not work as well as we would like with HIV. The AIDS virus uses macrophages as a storage chamber: without the ability to multiply in them, it is, however, able to wait out difficult times in the macrophage, evading both detection by the immune system and attacks by drugs. Researchers draw attention to the paradox associated with different forms of the HIV virus. HIV-2, unlike HIV-1, can turn off the SAMHD1 protein and quietly multiply in macrophages, but it is less virulent than HIV-1, which has to endure and wait for who knows what.
The researchers offer the following explanation for this paradox. Finding itself in difficult circumstances, HIV-1 is actively looking for a way out, that is, it receives carte blanche for all sorts of mutations: perhaps one of them will help cope with the resource limitation. At the same time, the virus is enriched with a set of mutations that increase its resistance to drugs, make it even more invisible to the body's defense systems, etc. That is, because of the starvation ration, the virus becomes even more brutal, and here it is already difficult to say whether the ability of macrophages to starve their prisoners is appropriate. However, the connection between the increased virulence of the virus and its starvation inside macrophages is still in the realm of hypotheses and requires additional experiments for confirmation.