Finding cure for HIV a balancing act

Student researching a group of protein that can shut down the virus.

Robin Love Robin Love (photo: Tara Donovan)

University of Saskatchewan researchers are studying a family of proteins produced in our own cells that can shut down HIV, the virus that causes AIDS.

But there's a catch: Te same proteins that could be harnessed to cure HIV can cause cancer in healthy cells.

The team is studying how this happens - knowledge that is critical for finding a treatment.

"The key is to strike a balance between how we could use our innate system to fight off HIV and how we can prevent it from turning on ourselves and causing cancer," U of S microbiology master's student Robin Love said.

The team's results show that the group of proteins, called APOBEC3, could be used to mutate the virus and render it non-infectious, ultimately breaking the transmission cycle.

But, as their recent publication in the Journal of Biological Chemistry shows, those same proteins can cause mutations in our own DNA that can lead to cancer.

Saskatchewan has the highest HIV infection rates in the country, with about 200 new cases diagnosed every year. HIV affects more than 34 million people worldwide.

Since the virus is spread through body fluids, intravenous drug users, sex-trade workers and children born to infected mothers are at highest risk for infection. Though there is no cure, an effective drug treatment regimen can increase the length and quality of life for someone living with AIDS. But the drugs have a serious drawback.

And since HIV mutates at such a high rate, monitoring, testing, and reinventing treatment plans for patients comes at a huge cost to the health-care system.

Love is part of a research team led by U of S microbiologist Linda Chelico. The team is among a few in the world using an intricate test-tube-based system to mimic HIV's natural replication.

This controlled system enables the team to investigate how the APOBEC3 family of proteins mutates DNA, such as that belonging to HIV.

Love's work has focused on two proteins in the APOBEC3 family which have evolved to prevent viral infection by causing lethal mutations in viruses such as HIV. An obvious treatment strategy would be to increase the level of APOBEC3 in cells.

But Love's research shows that excessive levels of APOBEC3 can cause cancer, so more research is needed before this approach can be considered the basis for a treatment.

"Although these proteins could prevent infection, many people become infected with the virus even when they are present," Love said.

"This says to us that in addition to viral defences, there are likely cellular mechanisms in place which keep these proteins in check so that they don't cause cancer."

Since the results have only been confirmed in a simulated environment, the team's next step is to determine how often these mutations occur in actual cells.

The research is funded by the Natural Sciences and Engineering Research Council, the Saskatchewan Health Research Foundation, and Canadian Institutes of Health Research.

Tara Donovan is a graduate student writer with the Students Promoting Awareness of Research Knowledge program of U of S Research Communications.

This article first ran as part of the 2012 Young Innovators series, an initiative of the U of S Research Communications office in partnership with the Saskatoon StarPhoenix.

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