Posted on May 3, 2018
“Cell-cell communication is one of the most ancient mechanisms that makes us who we are,” said Leonid Margolis, a Russian-born virologist at the National Institutes of Health. “Since vesicles resemble viruses, the question of course is whether the first extracellular vesicles were primitive viruses and the viruses learned from extracellular vesicles or vice versa.”
Whether cells started using vesicles for communication first and viruses copied them, or cells stole the idea from viruses, or both evolved the strategy in tandem is currently impossible to determine: Sending information in extracellular vesicles must have first appeared billions of years ago because even bacteria do it. “This idea of using a membrane-bound sac of information to transport between cells has been around a long time,” said David Meckes, Jr., a virologist at Florida State University.
For cells, continues Carrie Arnold in Quanta Magazine, communication is a matter of life and death. The ability to tell other members of your species — or other parts of the body — that food supplies are running low or that an invading pathogen is near can be the difference between survival and extinction. Scientists have known for decades that cells can secrete chemicals into their surroundings, releasing a free-floating message for all to read. More recently, however, scientists discovered that cells could package their molecular information in what are known as extracellular vesicles. Like notes passed by children in class, the information packaged in an extracellular vesicle is folded and delivered to the recipient.
The past five years have seen an explosion of research into extracellular vesicles. As scientists uncovered the secrets about how the vesicles are made, how they package their information and how they’re released, it became clear that there are powerful similarities between vesicles and viruses.
A small group of researchers, led by Margolis and Robert Gallo, the HIV pioneer at the University of Maryland School of Medicine, has proposed that this similarity is more than mere coincidence. It’s not just that viruses appear to hijack the cellular pathways used to make extracellular vesicles for their own production — or that cells have also taken on some viral components to use in their vesicles.
Extracellular vesicles and viruses, Margolis argues, are part of a continuum of membranous particles produced by cells. Between these two extremes are lipid-lined sacs filled with a variety of genetic material and proteins — some from hosts, some from viruses — that cells can use to send messages to one another.
“There are fundamental differences between viruses and vesicles: Viruses can replicate and vesicles cannot,” Margolis said. “But there are many variants in between. Where do viruses start, and where do extracellular vesicles start?”
One of the most striking pieces of evidence supporting Margolis and Gallo’s hypothesis is the recent discovery, widely reported in January, that a mammalian protein called Arc, which is implicated in learning and memory, is actually a repurposed retroviral protein. More important, Arc appears to be secreted from the synapses of neurons in extracellular vesicles. “These vesicles may be acting like a viral envelope,” said Cedric Feschotte, a retrotransposon expert at Cornell University.
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The image at the top of the page shows HERVs, the name for the ancient infectious viruses that inserted a DNA-based copy of their own RNA genetic material into our ancestors' genomes.
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