The new proteins are involved in the multiplication of AIDS inside the human cells and the scientists were able to take advantage of this to stop the spread. The discovery could lead to the creation of more innovative and effective drugs against AIDS
Viruses are small, minimalist creatures. The HIV virus, which causes AIDS, is no different. Its size does not exceed 100 nanometers (about a hundredth of the size of a typical human cell) and it contains only 9 genes, which code for the creation of only 15 proteins. But in a war against a virus, it would be a mistake to treat only these few proteins as hostile targets. The virus uses many human proteins to reproduce, and it is possible that in the future we will be able to develop drugs that will bind to the correct human proteins and prevent the virus from using them for its needs.
Researchers at Harvard Medical School used a technique called RNA interference (RNA silencing), in order to go over thousands of genes, and identified 273 human proteins that are necessary for HIV to multiply inside the cells. The discovery was published online in Science Express, and its importance comes from the fact Most of the proteins have not yet been identified as possible targets in the fight against AIDS.
The drugs in use today react directly with the virus itself. Despite their enormous effectiveness, a simple mutation on the part of the virus is enough to change the way it reacts with the drugs and thus evade them. Because the HIV virus evolves at a dizzying pace, there is no single drug capable of stopping the virus. AIDS patients take a cocktail containing a number Different drugs, so that even if the virus undergoes a mutation that neutralizes one drug, the other two can still kill it. At the same time, there is a great fear that at some point Strains of HIV will develop that are immune to the cocktail as well, since the virus is constantly evolving, it's only a matter of time.
"Antiviral drugs are doing a good job at the moment. They are keeping people alive. But they all have the same problem, that the virus can develop resistance against them. That's why we decided to try a different approach, focusing on the human proteins that the virus uses for its needs," says Stephen Elledge, the head of the research and a professor at Harvard Medical School. "The virus will not be able to undergo enough mutations in time to deal with drugs that affect these proteins."
In the last twenty years, laboratories around the world have advanced our understanding of the life cycle of the HIV virus. Dozens of human proteins have been identified, which the virus uses in order to multiply inside the cells. The new study builds on these understandings, and discovers over two hundred new human proteins necessary for the virus. Those proteins are responsible for a surprising number of cellular actions, starting with driving proteins inside the cell and ending with proteins that lead to programmed cell death.
The updated and expanded list of human proteins forms the basis for hundreds of possible new studies. According to Elledge, "Scientists can look at the list, predict why HIV needs a particular protein, and then test their hypothesis." He hopes that the research according to the list he created will produce new and effective drugs.
How did the researchers arrive at the extended list?
Avraham Brass, the lead author of the article and a postdoctoral researcher, used a pool of short interfering RNAs (siRNAs). Each of the strands targeted a specific human gene, and was able to effectively 'silence' the gene and prevent it from making the the protein it codes for.
Brass used research plates containing thousands of cells, in which he grew human cells. Each barit was injected with a different paralyzing RNA strand, directed against only one gene. Thus, the exact same cells were present in each barit - but in each barit, the cells did not express a different protein. In the next step, Brass sent the HIV virus into the cells in the bars. Brass noticed that in some of the bacteria the virus does not reproduce well, and from this he deduced the proteins whose disappearance interferes with the reproduction of the virus.
Of the 273 proteins revealed in the study, only 36 have previously been implicated in their involvement in the HIV life cycle. In order to verify the results, Brass selected three of the other 237 proteins, and put them through a series of rigorous genetic tests, which proved that they did play a role in the reproduction of HIV. Indirect proof was also obtained from the fact that the cells of the immune system - the same cells that HIV attacks - contain high concentrations of many of the 273 possible proteins.
"This is the first full genetic screening, trying to find human proteins that are needed for HIV, and we are confident that the results are correct," Brass says. "Most likely we missed a number of proteins, but most of the proteins we found are highly likely to be related to HIV and the way it reproduces."
"We're getting closer to a systemic understanding of HIV," Elledge adds. "With its help, we may be able to intervene and disrupt parts of the system to stop the AIDS culture, but without making our cells sick."
4 תגובות
In my opinion, it may not even be necessary to paralyze the protein, but only to change it in a way that prevents the virus from using it without harming its function in our body.
Evyatar,
The hope is that we will discover substances that are able to paralyze only one protein of the 273, and that the paralyzing of this protein will not interfere with the activity of the cells excessively - but it will lead to a complete stoppage of the virus.
But if we silence these 273 proteins in the cells of the human body or even a small part of them what will happen to the function of the human cells? If they exist in our cells then there must be a reason and we need these proteins in our cells.
It should also be mentioned that one of the researchers is an Israeli named Yair Benita