A Huge Discovery in the World of Viruses

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Your mouth is currently teeming with giant viruses that, until very recently, no one knew existed.

Unlike Ebola or the new coronavirus that’s currently making headlines, these particular viruses don’t cause disease in humans. They’re part of a group known as phages, which infect and kill bacteria. But while many phages are well studied, these newly discovered giants are largely mysterious. Why are they 10 times bigger than other phages? How do they reproduce? And what are they up to inside our bodies? “They’re in our saliva, and in our gut,” says Jill Banfield of the University of California, Berkeley, who led the team that discovered the new phages. “Who knows what they’re doing?”

From what Banfield and her team have been able to tell, though, these giants defy some fundamental ideas about how viruses usually work. And, even if it’s not yet clear how, they are likely affecting us.

Banfield’s team found the huge phages by accident. She and her colleagues were studying the gut bacteria of Bangladeshi people who live near arsenic-contaminated groundwater, to see whether those microbes can detoxify arsenic. They can’t. But among the bacterial DNA, the team also noticed the unexpectedly massive genomes of several new phages. An average phage carries about 52,000 “letters” worth of DNA, but these giants carried more than 540,000. And though the team first noticed them in Bangladeshi guts, they also found them in people from Tanzania, in pigs from Denmark, and in baboons from Kenya.

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Though common, these big phages would have been completely missed by traditional lab techniques. It used to be that scientists could only discover viruses by first growing them—and they often filtered out anything above a certain size. In science, you tend to find what you look for. The huge phages don’t fit the standard conception of what a virus should be, so no one went looking for them. But Banfield used a different method, which she pioneered in the 1990s: Her team took environmental samples—scoops of soil or drops of water—and simply analyzed all the DNA within to see what popped out. And once Banfield realized that the huge phages existed, it wasn’t hard to find more.

Her team, including researchers Basem Al-Shayeb and Rohan Sachdeva, identified huge phages in French lakes, in Tibetan springs, and on the Japanese seafloor. They found the viruses in geysers in Utah, salt from Chile’s Atacama Desert, stomach samples from Alaskan moose, a neonatal intensive-care unit in Pittsburgh, and spit samples from Californian women. All of these phages have at least 200,000 DNA letters in their genome, and the largest of them has 735,000.

The team included researchers from nine countries, and so named the new viruses using words for “huge” in their respective languages. Hence: Mahaphage (Sanskrit), Kaempephage (Danish), Kyodaiphage (Japanese), and Jabbarphage (Arabic), but also Whopperphage (American English).

These huge phages have other strange characteristics. With so much DNA, the viruses are probably physically bigger than typical phages, which means that they likely reproduce in unusual ways. When phages infect bacteria, they normally make hundreds of copies of themselves before exploding outwards. But Banfield says that an average bacterium doesn’t have enough room to host hundreds of huge phages. The giant viruses can probably only make a few copies of themselves at a time—a strategy more akin to that of humans or elephants, which only raise a few young at a time, than to the reproduction of rodents or most insects, which produce large numbers of offspring.

Giant phages also seem to exert more control over their bacterial hosts than a typical virus. All viruses co-opt their hosts’ resources to build more copies of themselves, but the huge phages seem to carry out “a much more thorough and directed takeover,” Banfield says. Their target is the ribosome—a manufacturing plant found in all living cells, which reads the information encoded in genes and uses that to build proteins. The huge phages seem equipped to fully commandeer the ribosome so that it ignores the host’s genes, and instead devotes itself to building viral proteins.

This takeover involves an unorthodox use of CRISPR. Long before humans discovered CRISPR and used it to edit DNA, bacteria invented it as a way of defending themselves against viruses. The bacteria store genetic snippets of phages that have previously attacked them, and use these to send destructive scissorlike enzymes after new waves of assailants. But Banfield’s team found that some huge phages have their own versions of CRISPR, which they use in two ways. First, they direct their own scissors at bacterial genes, which partly explains why they can so thoroughly take over the ribosomes of their hosts. Second, they seem to redirect the bacterial scissors into attacking other phages. They actually boost their hosts’ immune system to take out the competition.

All these behaviors are intriguing because they complicate the already heated debate about whether viruses should count as living things. Viruses share the same genetic material—DNA and RNA—that’s used in living cells, but cannot reproduce on their own and are completely dependent on their hosts. But in the complexity of their genomes, the giant phages certainly dwarf many organisms that are clearly alive—including bacteria that are also completely dependent on hosts for survival. Plus, the phages carry “all these bits of machinery that work with the ribosome and wouldn’t normally be in a nonliving thing,” Banfield says.

There are several reasons to find out more about these large viruses. For a start, phages have medical uses. In recent years, doctors have repeatedly used phages to treat bacterial infections that resisted all conventional antibiotics and seemed incurable. Beyond that, much of what we know about how genes work, and many technologies for altering and cloning said genes, came about through studying a phage called lambda. “Intensive research on phages founded the field of modern molecular biology,” says Bonnie Bassler of Princeton University. “I bet these megaphages house a treasure trove of new biological functions, which can be tinkered with to make applications that are useful for medicine, industry, or the environment.”

Future potential aside, the huge phages are almost certainly affecting us already. Phages control the communities of bacteria living in our bodies. They might defend us against dangerous microbes, or they could spread genes for resisting antibiotics among those microbes. Good or bad, parasite or mutualist, animate or inanimate: Phages seem to resist any possible classification. And they are clearly capable of more than scientists once expected. Just in the past few years, researchers have found phages that can eavesdrop on their hosts, and phages that protect their genes inside a capsule that looks uncannily like the nucleus of living cells.

“Every time we make new discoveries about the virosphere,” Mya Breitbart, of the University of South Florida, says, “it changes our perspective on what even constitutes a virus and how blurry the lines can be between viruses and cellular life.”