Virus Against Virus: Persuading an Infected Cell to Kill Itself

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Antiretroviral drugs have transformed HIV from a death sentence to a chronic disease, but with that comes with a daily cocktail of drugs to keep the virus at bay. These drugs are very efficient at blocking HIV replication, which limits damage to the immune system and increases survival time after an AIDS diagnosis. However, they can’t do anything about the DNA copy of the virus that has made its permanent home in each cell’s own DNA. Right now we don't have any way to get rid of that integrated virus, but researchers at USC are working on a method to get rid of the infected cells instead.

Chemical engineer Pin Wang has developed a modified viral vector—a biological mechanism used to transfer genetic information into a cell— that can mark HIV-infected cells for destruction by delivering a gene that will make the cell susceptible to a particular drug. The tricky part is selectively targeting infected cells while sparing the uninfected immune cells that are critical to fending off pathogens.

His solution is kind of like a backwards infection. Normally when HIV infects a cell, a specific protein on the virus's surface binds to the CD4 receptor, another protein, on the surface of T cells. T cells are a type of immune cell. Conversely, the HIV-killing vector in this study had CD4 on its surface, so that it could recognize the HIV surface proteins on infected T cells. Experiments showed that this vector was indeed finding the right cells—51% of the cells expressing the HIV surface protein received the vector, but the control cells without the HIV surface protein were left untouched.

The way the vector kills infected cells is by delivering a “suicide gene” that that turns a normally nontoxic drug, known as ganciclovir, toxic when it enters the cell. This way, after ganciclovir treatment, only the cells that received the vector will be killed. This is exactly what they saw:  there was no cell death in the control cells, while about 35% of the cells expressing the HIV surface protein were eradicated. This is good news when thinking about infected individuals, who will have a mixed population of infected and uninfected cells in their body.

So far these studies have only been done in vitro in dishes of cells, and similar studies are currently under way to improve the efficiency of the vector before the therapeutic potential of this approach could be considered. But, such a novel strategy to selectively eradicate infected cells is one addition to the HIV treatment toolbox that is incredibly exciting and absolutely needed. (More information about the study can be found here).

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