By all evidence, researchers say, viruses like Ebola have been parasitising living cells since the first cells arose on earth nearly four billion years ago. Some say viruses actually invented cells
Behind the hellish Ebola epidemic ravaging west Africa lies an agent that fittingly embodies the mad contradictions of a nightmare. It is alive yet dead, simple yet complex, mindless yet prophetic, seemingly able to anticipate our every move.
For scientists who study the evolution and behaviour of viruses, the Ebola pathogen is performing true to its vast, ancient and staggeringly diverse kind. By all evidence, researchers say, viruses have been parasitising living cells since the first cells arose on earth nearly four billion years ago.
Some researchers go so far as to suggest that viruses predate their hosts. That they essentially invented cells as a reliable and renewable resource they could then exploit for the sake of making new viral particles.
It was the primordial viral ‘collective’, says Luis P Villarreal, director of the Center for Virus Research at the University of California, Irvine, “that originated the capacity for life to be self-sustaining”.
“Viruses are not just these threatening or annoying parasitic agents,” he adds. “They’re the creative front of biology, where things get figured out, and they always have been.”
Researchers are deeply impressed by the depth and breadth of the viral universe, or virome. Viruses have managed to infiltrate the cells of every life form known to science. They infect animals, plants, bacteria, slime mould, even larger viruses. They replicate in their host cells so prodigiously and stream out into their surroundings so continuously that if you collected all the viral flotsam afloat in the world’s oceans, the combined tonnage would outweigh that of all the blue whales.
Not that viruses want to float freely. As so-called obligate parasites entirely dependent on host cells to replicate their tiny genomes and fabricate their protein packages newborn viruses, or virions, must find their way to fresh hosts or they will quickly fall apart, especially when exposed to sun, air or salt.
“Drying out is a death knell for viral particles,” says Lynn W Enquist, a virologist at Princeton.
How long shed virions can persist if kept moist and unbuffeted—for example, in soil or in body excretions like blood or vomit—is not always clear, but may be up to a week or two. That is why the sheets and clothing of Ebola patients must be treated as hazardous waste and surfaces hosed down with bleach.
Viruses are masters at making their way from host to host and cell to cell, using every possible channel. Whenever biologists discover a new way that body cells communicate with one another, sure enough, there’s a virus already tapping into exactly that circuit in its search for new meat.
Reporting recently in Proceedings of the National Academy of Sciences, Karla Kirkegaard, a professor of microbiology and genetics at Stanford University School of Medicine, and her colleagues described a kind of ‘unconventional secretion’ pathway based on so-called autophagy, or self-eating, in which cells digest small parts of themselves and release the pieces into their surroundings as signaling molecules targeted at other cells—telling them, for example, that it’s time for a new round of tissue growth.
The researchers determined that the poliovirus can exploit the autophagy conduit to cunning effect. Whereas it was long believed that new polio particles could exit their natal cell only by bursting it open and then seeking new cells to infect, the researchers found that the virions could piggyback to freedom along the autophagy pathway.
In that way, the virus could expand its infectious empire without destroying perfectly good viral factories en route. The researchers suspect that other so-called naked or non-enveloped viruses (like the cold virus and the enteroviruses that have lately plagued children in Asia) could likewise spread through unconventional secretion pathways.
For their part, viruses like Ebola have figured out how to slip in and out of cells without kicking up a fuss by cloaking themselves in a layer of greasy lipids stolen from the host cell membrane, rather as you might foist a pill down a pet’s throat by smearing it in butter.
According to Eric O Freed, the head of the virus-cell interaction section at the National Cancer Institute, several recent technological breakthroughs have revolutionised the study of viruses.
Advances in electron microscopy and super-resolved fluorescence microscopy—the subject of this year’s Nobel Prize in chemistry—allow scientists to track the movement of viral particles in and between cells, and to explore the fine atomic structure of a virus embraced by an antibody, or a virus clasped on to the protein lock of a cell.
Through ultrafast gene sequencing and targeted gene silencing techniques, researchers have identified genes critical to viral infection and drug resistance. “We’ve discovered viruses we didn’t even know existed,” Freed says. And that could prove important to detecting the emergence of a new lethal strain.
Gene sequencing has also allowed researchers to trace the deep background of viruses, which, at an average of a few billionths of an inch across, are far too minuscule to fossilise. In fact, viruses were first identified in the 19th century by size, as infectious agents able to pass through filters that trapped all bacteria.
Through genomic analysis, researchers have identified ancient viral codes embedded in the DNA of virtually every phyletic lineage. The unmistakable mark of a viral code? Instructions for making the capsid, the virus’s protective protein shell, which surrounds its genetic core and lends the viral particle its infectious power.
“It turns out there are not many ways to make the pieces that will snap together into an effective package,” says Enquist, of Princeton. “It’s an event that may have occurred only once or twice” in evolutionary history.
Viruses are also notable for what they lack. They have no ribosomes, the cellular components that fabricate the proteins that do all the work of keeping cells alive.
Instead, viruses carry instructions for co-opting the ribosomes of their host, and repurposing them to the job of churning out capsid and other viral proteins. Other host components are enlisted to help copy the instructions for building new viruses, in the form of DNA or RNA, and to install those concise nucleic texts in the newly constructed capsids.
“Viruses are almost miraculously devious,” Freed says. “They’re just bundles of protein and nucleic acid, and they’re able to get into cells and run the show.”
“On the one hand, they’re quite simple,” Enquist says. “On the other hand, they may be the most highly evolved form of genetic information on the planet.”
Viruses also work tirelessly to evade the immune system that seeks to destroy them. One of the deadliest features of the Ebola virus is its capacity to cripple the body’s first line of defense against a new pathogen, by blocking the release of interferon.
“That gives the virus a big advantage to grow and spread,” says Christopher F Basler, a professor of microbiology at Mount Sinai School of Medicine.
At the same time, says Aftab Ansari of Emory University School of Medicine, the virus disables the body’s coagulation system, leading to uncontrolled bleeding. By the time the body can rally its second line of defense, the adaptive immune system, it is often too late.
Yet the real lethality of Ebola, Ansari says, stems from a case of mistaken location, a zoonotic jump from wild animal to human being. The normal host for Ebola virus is the fruit bat, in which the virus replicates at a moderate pace without killing or noticeably sickening the bat.
“A perfect parasite is able to replicate and not kill its host,” Ansari says. “The Ebola virus is the perfect parasite for a bat.”