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Researchers Silence HIV in Mice Engineered to Be Like Humans

By stymieing three genes in cells infected with HIV, researchers stop the virus from spreading to other cells
HIV RNAI AIDS



© ISTOCKPHOTO/HENRIK JONSSON

Scientists report that they have quashed the spread of human immunodeficiency virus (HIV) in so-called "humanized mice" infected with the virus. They did so using a technique called RNA interference, or RNAi, to clamp down on three genes found in infected cells, blocking the wily virus from moving to other cells.

RNAi works by flooding a cell with short segments of RNA—the intermediate blueprint for building proteins from a gene's DNA. These segments disrupt the production of specific proteins, rendering a gene "silenced". In this case, that meant that three of HIV's dangerous proteins were not being made.

A Harvard Medical School team reports in the journal Cell that the RNAi method not only reduced the amount of virus in an infected mouse but also successfully prevented infection in healthy animals.

"This is a very potent antiviral mechanism," says study co-author Premlata Shankar, formerly a Harvard assistant professor now working as an immunologist at Texas Tech University's Health Sciences Center in El Paso. "If it can be harnessed for therapy, I am sure it could become a very good treatment for HIV."

Normally, mice cannot be infected with HIV, which only infects humans. The mice Shankar used, however, were engineered to be more like humans and could be infected with the virus. That means that the results have a better shot at translating to humans.

The researchers used RNAi to block three genes: two found in the virus itself and one found in mouse T cells—the primary immune system cells infected by the virus. The T cell gene codes for a protein that HIV uses to get into and infect a cell. The team hitched the RNA segments to an antibody—a protein that specifically seeks out and attaches to T cells—to deliver their cargo.

In mice already infected with HIV, the amount of virus in the blood dropped significantly two and a half weeks after treatment. "We saw that the viral load was low in these animals [after treatment]," says Shankar. "It means maybe you're blocking transmission into other cells."

In animals that researchers treated with RNAi, the virus never seemed to take hold.

Because the RNA segments degrade over time, Shankar explains, this treatment would have to be done repeatedly. She suggests that it may one day be used as a supplement to anti-HIV drugs that are on the market that may help to lessen the amount of drugs—and side effects—patients have to put up with.

John Rossi, a molecular biologist at the Beckman Research Institute in Duarte, Calif., who was not involved in the research, noted that from his own work, using RNAi to treat T cells may allow patients to significantly reduce the dosage of the anti-HIV drugs—up to 100-fold. He agreed with Shankar that the RNAi method would not lead to a stand-alone treatment "The virus goes beyond T cells," he says, noting that it attacks several other types of immune cells. "It might be that the antibody is not going to get at these other cells, so it might not work without other antiretrovirals."

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