To infect a cell, HIV neutralizes their protection. A strategy that does not work in all cases thanks to a protein on the surface of the cells.
Over the course of its evolution, the AIDS virus has implemented many strategies to infect the cells of our body. Adaptation mechanisms essential to escape the immune system and thwart the protection put in place by cells.
Among these processes, the viral protein Nef plays a crucial role. “When the AIDS virus replicates in a cell, it uses Nef to neutralize the proteins responsible for protecting cells,” explains Federico Santoni, a bioinformatician at the University of Geneva and co-author of the study.
However, other proteins are capable of inactivating Nef. The AIDS virus is then weakened and cannot enter the cells to infect them. A team of Swiss and Italian researchers have joined forces to discover the cellular proteins responsible. Their results have been published in the prestigious journal Nature.
The aim of our work was therefore to identify these unknown proteins in order to understand why certain cells are more susceptible than others to HIV, ”adds Federico Santoni.
A new therapeutic avenue
By studying different cell lines, the researchers identified SERINC5, a membrane protein capable of blocking HIV infection. “The infection mechanism takes place in two stages,” explains Massimo Pizzato, virologist specializing in HIV at the University of Trento (Italy) and study coordinator.
When the virus enters the cell to infect it, it gets there without any problem. But when it comes out of the cell to infect another, it takes a piece of the cell membrane with it. It then carries the SERINC5 protein on its surface. From there, as soon as it tries to infect another cell, this protein acts as a warning signal and alerts the cell. HIV can therefore no longer enter the cell ”. This is why HIV has implemented the Nef protein capable of neutralizing SERINC5.
However, the researchers found that cells expressing strongly SERINC5 are protected against HIV because Nef is no longer able to neutralize it. “We must continue to work on defense mechanisms in order to assess how they can be exploited to develop new therapeutic strategies. We could reinforce the presence of SERINC5 in all cells or modify its structure to prevent it from being deactivated by Nef ”, suggests Federico Santoni.
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