Scientists unravel biggest mystery of HIV

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http://english.pravda.ru/science/mysteries/13-11-2013/126126-aids_mystery-0/

Scientists have finally found a way to outsmart the human immunodeficiency virus (HIV), or rather, its ability to hide from the antibodies and immune cells. This is the quality that makes HIV so dangerous. However, researchers were able to find a way to create an effective cure for AIDS using the substance tacrolimus and finally win over the dangerous disease.

The main difficulty against the human immunodeficiency virus (responsible for such a scary disease as acquired immunodeficiency syndrome) is that this malicious virus is completely elusive for human immune system. One gets the impression that it has some kind of invisibility power where antibodies cannot recognize it. A fairly strong variability of the HIV protein is to blame. This is precisely why the immune system is unable to develop antibodies that could "identify and detain" the virus exiting the cell.

However, in principle, there is another way of neutralizing HIV. The immune system can do it when the virus is still in the cell. All cells of the body have a semblance of integrated alarm activated when a pathogen enters a cell and start reproducing. Each infectious agent, be it a virus or a bacterium, penetrates the cell to bring along its own set of molecules that interact with cellular substances and activate the alarm. This signal represented by a chemical reaction rapidly comes to the immune system, attracting antibodies to the infected cell.

This is the usual way of neutralization of many viruses and bacteria that manage to get into cells, but it does not work with HIV. When penetrating a cell, this virus begins to breed, and manages to remain invisible to the alarm system. It was completely unclear how the virus manages to do it. However, the observations showed that the infected cell behaves as a healthy one, and therefore antibodies are not interested in it. How does the HIV achieve this effect? Recently, biologist Greg Towers and his colleagues at University College of London (UK) were able to figure it out. After a series of experiments, the researchers found that HIV, once in a cell, binds to three proteins, one of which is required for the maturation of mRNA, and the other two belong to the immune protein cyclophilin.

This is precisely what disables the cell signaling. In fact, mRNAs are involved in antiviral responses, preventing reading the information from the DNA of a virus. Cyclophilins provide interferon protection of a cell by triggering the synthesis of proteins from a group of interferons that, exiting the infected cell, come in contact with its neighbors, encouraging them to "produce" mRNAs and other cellular antiviral "drugs." That is, in fact, the interferon response is a major component of the cell alarm system.

The immunodeficiency virus associated with these proteins inhibits their activity. But is it possible to prevent this process? Biologists have conducted a series of experiments where they managed to do it. They removed one of the cyclophilin from the cells, replacing it with an analog cyclosporine - cyclic polypeptide consisting of 11 amino acids produced by soil fungi species Beauveria nivea. It has been long known that cyclosporine is a potent immunosuppressive agent capable of providing artificial immunosuppression, so it is often used for preventing rejection in transplantation of organs and tissues.

However, cyclosporine has another useful characteristic. They can bind to the proteins that HIV uses to become "invisible" to antibodies. The question was only in the selection of the analogue also capable of binding to these proteins, but without suppressing the immune response. After a series of trial runs, Dr. Towers and his colleagues were able to obtain a similar substance. As a result, when it was added to the infected cell, on the one hand, it blocked the attempts of HIV to bind the required proteins, and on the other hand did not suppress the activity of the proteins, so the interferon signaling worked. The cells quickly recognized the infected cell and destroyed it before the virus has had time to propagate.

Scientists believe that such material could in principle be an effective medicine against AIDS. However, scientists immediately notice that it cannot operate on its own, but only in conjunction with effective antibodies. Now they need to produce more antibodies immediately capable of identifying the proteins of the malicious virus.