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.
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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.