Researchers in the making:
New hope in gene therapy
A former AHFMR Fellow has found a gene that may be able to block HIV.
Story by Tara Narwani/Illustration by Brennan Kelly
The human immunodeficiency virus (HIV), the virus that causes AIDS, is a sneaky biological enemy. It inserts its own genetic material into certain cells that are indispensable to our immune system-after which the virus cannot be removed. Once HIV infects a person, they're infected for life. "In essence, HIV hides in our bodies, so we can't get rid of it completely," explains Calgary-born virologist Dr. Stephen Barr. This makes finding a cure for AIDS a very difficult prospect.
The challenge doesn't stop there. Researchers have to stay one step ahead of the virus to maintain effective drug treatments. "When HIV replicates, it undergoes a lot of mutations. Since drugs are designed to target a very specific part of the virus, they lose their effectiveness as the virus mutates," Dr. Barr says.
Over the past 20 years, research has answered a lot of questions about how HIV is transmitted and how it infects the body. By contrast, it has revealed very little about how the body naturally defends itself against HIV infection. Identifying key components of our immune response to HIV could yield new forms of drug treatment. Dr. Barr pursued this quest during his AHFMR-supported post-doctoral work at the University of Pennsylvania and the University of Alberta, and he found something quite promising.
Dr. Barr examined the central question of whether the human body activates a gene (or set of genes) in response to an HIV attack. "If we can find a natural gene that attacks HIV, maybe we can develop a gene-based therapy and avoid the use of toxic drugs."
Amazingly, previous studies had shown that HIV infection could be stopped in human cells of a certain type, but only after these cells had been exposed to a protein called interferon. Interferon normally plays the role of messenger, alerting the body when a virus tries to infect it.
These results provided an important clue. Dr. Barr knew that interferon "turns on" certain genes that can protect the cell from HIV. But his experiments showed that more than 50 genes are activated-too many for one researcher to investigate further.
One gene in particular, however, caught his attention: TRIM22. In 2004, around the time Dr. Barr began his research project, a report was published claiming that a gene from the rhesus monkey, when activated, could block HIV infection. This gene was called TRIM5. "Interestingly, the human form of TRIM5 was ineffective against HIV. Since there are unknown risks associated with inserting a gene from another species, or even from another human being, into the body for therapy, we started thinking that maybe there's another TRIM gene that can do something similar in humans," Dr. Barr recalls.
When TRIM22 came up as one of the genes turned on by interferon, he knew where to focus his attention.
Earlier this year, Dr. Barr published his conclusions about what the protein produced by the TRIM22 gene, TRIM22 (the protein is indicated without italics upper case letters as TRIM22), does in a laboratory setting. "It acts by trapping HIV within the cell. This is an exciting finding because, if the virus can't get out of the cell, it would be prevented from spreading, and the onset of AIDS would be slowed or even prevented."
What's still unclear is this: If we humans have this gene, why do we get infected with HIV? Can HIV target TRIM22 and destroy it? Does something prevent the gene from being properly activated in infected individuals?
These are all questions that Dr. Barr would like to pursue in his new faculty position at the University of Western Ontario. He's optimistic that his work could lead to a new drug treatment for HIV infections. "There's still a lot more research that needs to be done, particularly on the interactions of TRIM22 with HIV proteins. If we can figure out exactly how TRIM22 traps HIV inside cells, then we can try to develop a strategy to mimic that effect."