Many of the deadly viruses that affect humans—including Ebola and HIV—have animal origins. These infectious agents cross species barriers and establish themselves in their new human hosts with devastating consequences.
Take Ebola, for example. Bats were thought to be the original reservoirs for the viruses, which transmitted the pathogens to other animals, including apes and monkeys. During what's known as a spillover event, humans became infected when they hunted and ate sick animals. Subsequently, outbreaks of Ebola virus disease spread rapidly among vulnerable communities, killing tens of thousands.
In search of new clinical interventions against such infections, virologists are taking a closer look at these viruses' original hosts and making remarkable discoveries. A team of researchers from the University of Utah Health and Rockefeller University teamed up to examine how monkeys' immune systems help resist viral attacks.
The team, led by an evolutionary geneticist, Nels Elde, discovered a monkey gene called retroCHMP3 that acts as a security checkpoint, blocking certain viruses from exiting infected cells. This action prevents the infection from ravaging healthy tissues. The team reported their findings in the journal Cell.
After entering a cell and depositing its genetic material inside, some viruses slip into cell membranes to make a stealthy exit towards neighboring cells. Elde and colleagues discovered that retroCHMP3 stalls the virus' departure, keeping it trapped within the already infected cell.
The team genetically engineered human cells to express a modified version of monkey retroCHMP3. They found that when they infected these engineered cells with HIV, the virus stayed put, unable to bud off and spread. This virus 'trapping' occurred without any observable side effects on normal cell physiology and cell signaling.
According to Elde, this was an unexpected find with important implications on warding off viral infections in humans therapeutically. "We were surprised that slowing down our cell biology just a little bit throws virus replication off its game," Elde commented.
The researchers had previously shown that this viral escape strategy, known as the ESCRT pathway, was the modus operandi of several enveloped viruses. This work led the scientists to hypothesize that cells might adapt to acquire means of defending themselves against viral spreading. The discovery of retroCHMP3 has affirmed their suspicions, paving the way for drugs that mimic this pathway, keeping dangerous viruses localized within the boundaries of already compromised cells.