US researchers have determined how a genetic mutation found in mice and monkeys can help develop medical interventions against viruses such as HIV and Ebola in humans.
The gene, called retroCHMP3, encodes an altered protein that disrupts the ability of certain viruses to exit an infected cell and prevents it from going on to infect other cells.
Normally, some viruses encase themselves in cell membranes and then make an exit by budding off from the host cell. RetroCHMP3 delays that process long enough that the virus can no longer escape.
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"This was an unexpected discovery," said Nels Elde, an evolutionary geneticist in the Department of Human Genetics at the University of Utah.
"We were surprised that slowing down our cell biology just a little bit throws virus replication off its game," Elde said, in the paper published in the journal Cell.
RetroCHMP3 originated as a duplicated copy of a gene called charged multivesicular body protein 3, or CHMP3. While some monkeys, mice, and other animals have retroCHMP3 or other variants, humans only have the original CHMP3.
In humans and other creatures, CHMP3 is well known for playing a key part of a role in cellular processes that are vital for maintaining cellular membrane integrity, intercellular signalling, and cell division.
HIV and certain other viruses hijack this pathway to bud off from the cellular membrane and infect other cells. Based on their research, the team suspected that the duplications of CHMP3 they discovered in primates and mice blocked this from happening as protection against viruses like HIV and other viral diseases.
Building on this notion, the scientists began exploring whether variants of retroCHMP3 might work as an antiviral. In laboratory experiments conducted elsewhere, a shorter, altered version of human CHMP3 successfully prevented HIV from budding off cells. But the modified protein also disrupted important cellular functions, causing the cells to die.
Further, using genetic tools, the team coaxed human cells to produce the version of retroCHMP3 found in squirrel monkeys. Then, they infected the cells with HIV and found that the virus had difficulty budding off from the cells, essentially stopping them in their tracks. And this occurred without disrupting metabolic signalling or related cellular functions that can cause cell death.
Elde believes this represents a new type of immunity that can arise quickly to protect against short-lived threats.