‘Retro’ gene found in monkeys may lead to immunity against HIV, other viral diseases

SALT LAKE CITY — A gene found in animals could be the key to stopping viruses, including HIV and Ebola, dead in their tracks, according to a new study. The genetic mutation, dubbed “retroCHMP3,” prevents certain viruses from spreading by trapping them inside the cell’s membrane, say scientists. While humans do have the CHMP3 gene, we do not have the “retro” variant, which is only found in monkeys, mice, and some other animals.

Most viruses enclose themselves in cell membranes before budding off to infect other healthy cells in the body. Now, researchers at the University of Utah Health and Rockefeller University have found a way to prevent viruses from exploiting this “Achilles heel.” Their discovery could help provide people with immunity against certain viral diseases in the future.

“This was an unexpected discovery. We were surprised that slowing down our cell biology just a little bit throws virus replication off its game,” says study senior author Dr. Nels Elde, in a statement.

Scientists have known for some time that CHMP3 plays an important role in everyday cellular processes. For example, it’s vital for maintaining cell membrane integrity, intercellular signaling, and cell division. But HIV and certain other viruses can hijack these processes in order to exit the cellular membrane and infect other cells.

Laboratory experiments were carried out to see whether one of the retroCHMP3 variant might work as an antiviral in humans. Shorter, altered versions of human CHMP3 successfully prevented HIV from exiting the cell, the researchers found, but there was a glitch. The variants also disrupted other important cellular functions, eventually causing the cells to die.

To remedy this, the researchers used genetic tools to coax human cells into producing a version of retroCHMP3 that is found in squirrel monkeys. They then infected the cells with HIV and found the virus struggled to spread, except this time no other processes were affected.

“We’re excited about the work because we showed some time ago that many different enveloped viruses use this pathway, called the ESCRT pathway, to escape cells. We always thought that this might be a point at which cells could defend themselves against such viruses, but we didn’t see how that could happen without interfering with other very important cellular functions,” study author Dr. Wes Sundquist says.

From an evolutionary standpoint, these genetic variations could represent a new type of immunity, which can arise quickly to counter short-lived threats. “We thought the ESCRT pathway was an Achilles heel that viruses like HIV and Ebola could always exploit as they bud off and infect new cells. RetroCHMP3 flipped the script, making the viruses vulnerable. Moving forward, we hope to learn from this lesson and use it to counter viral diseases,” said Dr. Elde.

“It raises the possibility that an intervention that slows down the process may be inconsequential for the host, but provide us with a new anti-retroviral,” study co-author professor Sanford Simon adds.

The findings are published in the journal Cell.

South West News Service writer Tom Campbell contributed to this report.