Immune response to HIV virus linked to cancer mutations

October 25, 2017 by Federica Giannelli, University of Saskatchewan
Madison Adolph and Linda Chelico (left) uncovered how enzymes in the immune system may “go rogue” and cause cancer. Credit: David Stobbe

"Our findings could change the way we treat cancer," said microbiology professor Linda Chelico. Her research, funded by the federal agency NSERC, was recently published in Nucleic Acids Research and a related project was published in Nature Communications.

Chelico and PhD student Madison Adolph have found evidence that three enzymes in the APOBEC3 family, which guards the immune system with seven enzymes in total, may "go rogue," triggering in human DNA that may lead to over time.

The results could open up the possibility for developing inhibitors that suppress these enzymes when they malfunction, or developing special tests to monitor their levels in the body.

Scientists have previously known that these enzymes are linked to and may also appear in cancer patients not infected by viruses. But until now they had not known how the enzymes mutated the human genome.

"The enzymes we study are very important for building a defence against viruses, but some specifically activated to fight HIV infection may end up being expressed in the wrong place at the wrong time, causing unintended mutations," said Chelico.

The enzymes bind to the DNA of the HIV virus and try to mutate it to shut down the virus replication in the body. But HIV has its own defence mechanism.

Unable to fight HIV, the enzymes keep scanning human DNA and may incorrectly get turned on in the wrong cell type, causing mutations to healthy cells. This happens even in the presence of the body's repair mechanisms that are supposed to protect human DNA from damage.

"This is off-target behavior for the enzymes because they typically attack only single-stranded virus DNA," said Adolph. "We have identified for the first time the biochemical features that allow these enzymes to bind to tiny regions of human DNA that are single-stranded."

Adolph spent the past four years trying to isolate from cells the APOBEC3B, the main contributor to these mutations, and was unsuccessful for a long time. But she did not give up because she knew the process was key to understanding the mechanisms behind these enzymes.

"We were the first research team to study these enzymes outside cells, which is their natural environment. We were able to analyze how they cause mutations, instead of looking at already mutated cancer genomes as previous researchers did," said Adolph.

Despite the promising results, the researchers caution that what triggers the malfunction of the enzymes is still unknown. The U of S team has yet to establish whether the enzymes initiate cancer or make it worse by causing further mutations to the DNA of cells.

"We have started a new research phase where we mix healthy and these enzymes together in the lab to see what happens, but we are still at a very early stage," said Chelico.

Explore further: On the other hand, the immune system can also cause cancer

Related Stories

On the other hand, the immune system can also cause cancer

August 23, 2017
Infection with human papillomavirus (HPV) is the primary cause of cervical cancer and a subset of head and neck cancers worldwide. A University of Colorado Cancer Center paper describes a fascinating mechanism that links ...

An unexpected role for epigenetic enzymes in cancer

December 6, 2016
To better understand how cancer initiates and spreads, Yale associate professor of pathology Qin Yan turned to the field of epigenetics, which examines changes in the expression of genes and proteins that do not affect the ...

New studies create better understanding of cancer-spreading enzymes

December 2, 2015
As a part of the human immune system, white blood cells create a number of enzymes that help fight disease. Sometimes, these enzymes can malfunction, causing damage to the body or increasing cancer growth. Now, researchers ...

Researchers provide molecular portraits of a new cancer drug target

December 19, 2016
Unprecedented images of cancer genome-mutating enzymes acting on DNA provide vital clues into how the enzymes work to promote tumor evolution and drive poor disease outcomes. These images, revealed by University of Minnesota ...

Recommended for you

Cancer comes back all jacked up on stem cells

March 19, 2018
After a biopsy or surgery, doctors often get a molecular snapshot of a patient's tumor. This snapshot is important - knowing the genetics that cause a cancer can help match a patient with a genetically-targeted treatment. ...

A small, daily dose of Viagra may reduce colorectal cancer risk

March 19, 2018
A small, daily dose of Viagra significantly reduces colorectal cancer risk in an animal model that is genetically predetermined to have the third leading cause of cancer death, scientists report.

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...

Joint supplement speeds melanoma cell growth

March 15, 2018
Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.