AIDS: the virus uses a protein of the cell to protect itself

To stay out of reach of defenses that own each of our cells, the AIDS virus (HIV) captures a protein that is very abundant and integrates it into its arsenal, allowing it to gain stability. This discovery, made by an Australian team and published in the journal eLife helps to elucidate some of the great mystery surrounding the process of HIV infection. Ultimately, these results will lead to new therapeutic strategies.

HIV, a virus protected by a mysterious "armor"

HIV uses what it finds in host cells to multiply. Thus, it invades the cells and transforms their genetic material into DNA, which it can then integrate with that of the cell, in its nucleus. The cell will then "read" and treat this DNA as its own, that is to say by producing the corresponding proteins. The viral proteins will then form new viruses that will emerge from the cell to infect others.

The virus must however protect its genome against the detection and destruction of the active defense molecules within the cell time to reach the nucleus. HIV surrounds itself with an envelope of proteins called capsids. The structure of this capsid is very complex: indeed, it must be strong enough to withstand several hours inside the cell time to transform its genetic material, but not too much because it must be able to break to release its genome in the nucleus when the time comes. The way this process, called "unpacking", is done is one of the big unanswered questions in HIV biology.

HIV uses the IP6 protein, naturally present in the cell, to stabilize its protection system

In this new study, researchers designed viruses with fluorescent tags to monitor the viral capsid using fluorescence microscopy. " We can now see the effect of different molecules on the capsid, and accurately identify when it opens up and begins to collapse ", explains Professor Till Böcking, who participated in this work in a statement. Indeed, the capsid studied alone in the laboratory decomposes very rapidly, forcing researchers to study it in infected cells. The scientists then observe that the virus integrates into its capsid a protein belonging to the host cell. Called inositol hexakisphosphate (or IP6), it is naturally very abundant and binds to the pores present on the capsid to stabilize it for 10 to 20 hours. " It's like a switch: when you bind this molecule, you stabilize the capsid, and when you release it, you open it ," says Pr Till Böcking.

[19659004] HIV captivity. In magenta, the binding sites of the IP6. Credits: UNSW

RESEARCH AND TREATMENT . This work is important because it will allow researchers to better study the viral capsid. Thus, by adding IP6, they can theoretically stabilize it long enough for their experiments. Moreover, this discovery " provides a new dependence to exploit in the development of antiviral treatment ," according to the authors. Most currently approved anti-HIV therapies target the necessary proteins at different stages of the life cycle of the virus, but none are directed against the HIV capsid.