Cancer Mutations Triggered When Immune System Fights HIV?

According to a new study published by Nature Communications, when combatting viruses such as HIV, several enzymes in the immune system may malfunction and cause cancer-related mutations.

“Our findings could change the way we treat cancer,” said investigator Linda Chelico, PhD.

The investigators discovered that 3 enzymes in the APOBEC3 family trigger these mutations, despite their duties to protect the immune system. These findings may lead to novel inhibitors that suppress the enzymes or tests to determine their levels.

Previous research showed that the enzymes were linked with cancer mutations and may be present in patients with cancer who are not fighting viruses. However, the new study is the first that shows how the enzymes are able to mutate DNA.

“The enzymes we study are very important for building a defense 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,” Dr Chelico said.

The investigators stated that enzymes bind to HIV DNA in order to mutate it and inhibit viral replication, but HIV is notoriously difficult to kill.

Because the enzymes are unable to combat HIV, they continue to scan DNA and may incorrectly cause mutations to healthy cells, according to the study. This process was observed to happen despite the presence of repair mechanisms that protect DNA.

“This is off-target behavior for the enzymes because they typically attack only single-stranded virus DNA,” said investigator and PhD student, Madison 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.”

The investigators previously attempted to isolate cells from the APOBEC3B enzyme since it was a critical factor in understanding the enzymes, according to the study.

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

Although these results are promising, the authors caution that the process that causes the cancer-related mutations is still unknown. The investigators also have yet to determine whether the enzyme mutations cause cancer directly or just increase risk, according to the study.

A previous version of this article was published on SpecialtyPharmacyTimes.com.