[還不清楚是否和疾病有關]
Changing View on Viruses: Not So Small After All
Chantal Abergel and Jean-Michel Claverie
Electron microscopy image of a Pandoravirus particle. The virus is 1,000 times bigger than the flu virus and has nearly 200 times as many genes.
By CARL ZIMMER
Published: July 18, 2013
There was a time not that long ago when it was easy to tell the difference between viruses and the rest of life. Most obviously, viruses were tiny and genetically simple. The influenza virus, for example, measures about 100 nanometers across, and has just 13 genes.
Those two standards, it’s now clear, belong in the trash. Over the past decade, scientists have discovered a vast menagerie of viruses that are far bigger, and which carry enormous arsenals of genes. French researchers are now reporting the discovery of the biggest virus yet. The pandoravirus, as they’ve dubbed it, is 1,000 times bigger than the flu virus by volume and has nearly 200 times as many genes — 2,556 all told.
Making the discovery all the more startling is the fact that, of all the genes that pandoraviruses carry, only six percent match any gene known to science.
“We believe we’re opening a Pandora’s box – not so much for humanity but for dogma about viruses,” said Dr. Jean-Michel Claverie of the University of Mediterranée, co-author of the paper that was published online Thursday in the journal Science. “We believe we’re touching an alternative tree of life.”
Giant viruses would be important enough simply for the way they have blurred the line between viruses and the rest of life. But they excite scientists for another reason. Utterly unknown a decade ago, they turn out to be everywhere, including in our own bodies. What effect they have on the world’s ecosystem — or our own health — is anyone’s guess right now.
It was the very giant-ness of giant viruses that allowed them to be overlooked for so long. Scientists first discovered viruses in the late 1800s when they were puzzled by a disease that beset tobacco plants. They mashed up wilted tobacco leaves with water and passed the mixture through fine porcelain filters that trapped bacteria and fungi. The clear liquid could still make healthy tobacco leaves sick. The Dutch botanist Martinus Beijerinck dubbed it “a contagious living fluid.”
In the 1930s, the invention of powerful microscopes finally allowed scientists to see viruses. They found that viruses were unlike ordinary cells: they didn’t generate their own fuel; they didn’t grow or divide. Instead, viruses invaded cells, hijacking their biochemistry to make new copies of themselves. Being small and simple seemed like part of the viral way of life, allowing them to replicate fast.
It wasn’t until 2003 that a team of French researchers discovered the first giant virus. They had been puzzling over sphere-shaped objects that were the size of bacteria but contained no bacterial DNA. Eventually they realized that they were looking at a monstrously oversized virus, containing 979 genes.
Those first giant viruses were isolated from amoebae living in water from a cooling tower. Once scientists realized that viruses could be so large, they changed their search parameters and started finding other species in all manner of places, from swamps to rivers to contact lens fluid.
And along the way the biggest viruses got bigger. In 2011, Dr. Claverie and his colleagues set a new record with megaviruses, a type of giant virus with 1,120 genes they discovered in sea water off the coast of Chile. They then dug into the sediment below that sea water and discovered pandoravirsues, with more than twice as many genes.
Dr. Claverie speculates that pandoraviruses and other giant viruses evolved from free-living microbes that branched off from other life several billion years ago. “The type of cells they may have evolved from may have disappeared,” he said.
The idea that giant viruses represent separate branches on the tree of life is a controversial one that many other experts aren’t ready to embrace. “They provide no evidence for that notion, so it seems a distraction to me,” said T. Martin Embley, a professor of evolutionary molecular biology at Newcastle University.
Despite those reservations, Dr. Embley and other researchers hail pandoraviruses as an important discovery. “I think it’s wonderful that such crazy and divergent lifeforms continue to be discovered,” said Tom Williams, Dr. Embley’s colleague at Newcastle University.
The new study also drives home the fact that giant viruses are far from rare. Shortly after discovering pandoraviruses in sea floor sediment, Dr. Claverie and his colleagues found them in water from a lake in Australia, 10,000 miles away. “It definitely indicates that they must not be rare at all,” said Dr. Claverie.
Giant viruses may be so common, in fact, that they may be hiding inside of us, too. In a paper published online on July 2 in The Journal of Infectious Diseases, French researchers offered evidence that giant viruses dwell in healthy people. They isolated a new giant virus from blood donated by a healthy volunteer, and then found antibodies and other signs of the virus in four other donors.
Giant viruses may lurk harmlessly in our bodies, invading the amoebae we harbor. Whether they can make us sick is an open question. “I don’t believe we have the proof at the moment that these viruses could infect humans,” said Dr. Claverie.
“But again,” he added, “never say never.”
That’s wise advice when it comes to giant viruses.
Giant viruses, more than twice as big as the last largest known viruses, have now been unearthed from sludge across the world, researchers say.
Even more titanic viruses might await discovery, the scientists said, and they may have features that could blur the lines between life and viruses, which are not considered to be living things.
Ten years ago, researchers accidentally discovered mimivirus, what until now was the biggest, most complex virus known. Mimivirus — a name derived from "mimicking microbes," chosen because the viruses were nearly the size of some bacteria — and its relatives the megaviruses can reach sizes of more than 700 nanometers (a nanometer is one billionth of a meter), and possess more than 1,000 genes, features typical of parasitic bacteria. Typical viruses are maybe 20 to 300 nanometers large, and many viruses, such as influenza or HIV, get along very well with 10 or fewer genes.
Now the research team that discovered those giant viruses have unearthed two more that are even bigger. The shape of these new viruses, which resemble ancient Greek jars, reminded the scientists of the myth of Pandora's box, giving the germs their name — pandoraviruses.
"The opening of the box will definitively break the foundations of what we thought viruses were," researcher Chantal Abergel, research director at the French National Center for Scientific Research in Marseille, told LiveScience.
The new record-breaking viruses are visible with a traditional light microscope, being a full micrometer or millionth of a meter in size, or approximately a hundredth the width of a human hair. They also each possess a whopping roughly 2,500 genes.
"We were prepared to find new viruses in the 1,000-gene range, but not to more than double that figure," Abergel said. "This really indicates than we don't know what are the possible limits anymore."
Megaviruses, which initially were mistaken for bacteria, were discovered in amoebas, and the investigators found pandoraviruses by also looking at amoebas. One virus, named Pandoravirus salinus, was unearthed at the mouth of the Tunquen River off the coast of central Chile, while the other, called Pandoravirus dulcis, dwelled at the bottom of a shallow freshwater pond near Melbourne, Australia. (Pandoravirus-like particles were actually first observed about 13 years ago, but were not recognized as viruses at the time.)
Two to four hours after amoebas engulf these pandoraviruses, the nucleus of the amoebas begins transforming radically, ultimately vanishing. When the amoebas finally die, they each unleash about 100 pandoraviruses. [Tiny Grandeur: Stunning Photos of the Very Small]
The amoebas the researchers used in their experiments are probably not the natural hosts for these viruses; rather, the main targets of these viruses may be protozoa or algae that are typically very difficult to grow and maintain in labs.
The scientists used amoebas instead because they can grow in labs, and gorge on their surroundings in a very indiscriminate way, sweeping most anything into themselves as they look for potential food. "This is why they are a very good target for capturing giant viruses," Abergel said.
More than 93 percent of pandoravirus genes resemble nothing known. This makes their origins a mystery — analysis of their genomes suggests pandoraviruses are not related to any known virus family.
"These viruses have more than 2,000 new genes coding for proteins and enzymes that do unknown things," Abergel said. "Elucidating their biochemical and regulatory functions might be of tremendous interest for biotech and biomedical applications. We want to propose a full large-scale functional genomics project on the pandoravirus genomes."
The fact that pandoraviruses are totally different from the previously known family of giant viruses may suggest even more families of giant viruses remain to be discovered, said researcher Jean-Michel Claverie, head of the Structural and Genomic Information Laboratory in Marseille, France.
"Our knowledge of the microbial biodiversity on this planet is still very partial," Claverie said. "Huge discoveries remain to be made at the most fundamental level that may change our present scenario about the origin of life and its evolution."
It remains a mystery why pandoraviruses have more than 2,500 genes while most viruseshave far less, the researchers said. One controversial suggestion the researchers make is that giant viruses and other viruses that depend on DNA as their genetic material may be the shrunken descendants of living, cellular ancestors.
"Parasites of any kind are submitted to the universal process of 'genome reduction' — that is, they may lose genes without harm, because the host can always provide the missing function," Claverie said. DNA viruses small and giant may all have degenerated from the same or similar cellular ancestors, "but only differ by the rate by which they lost genes from the starting ancestral genome," he said.
Future research could turn up "even more intermediary life forms between viruses and cells, establishing a continuity between the two," Abergel said. "How should we define the boundaries between cells and viruses?"
The scientists detailed their findings in the July 19 issue of the journal Science.
Making the discovery all the more startling is the fact that, of all the genes that pandoraviruses carry, only six percent match any gene known to science.
“We believe we’re opening a Pandora’s box – not so much for humanity but for dogma about viruses,” said Dr. Jean-Michel Claverie of the University of Mediterranée, co-author of the paper that was published online Thursday in the journal Science. “We believe we’re touching an alternative tree of life.”
Giant viruses would be important enough simply for the way they have blurred the line between viruses and the rest of life. But they excite scientists for another reason. Utterly unknown a decade ago, they turn out to be everywhere, including in our own bodies. What effect they have on the world’s ecosystem — or our own health — is anyone’s guess right now.
It was the very giant-ness of giant viruses that allowed them to be overlooked for so long. Scientists first discovered viruses in the late 1800s when they were puzzled by a disease that beset tobacco plants. They mashed up wilted tobacco leaves with water and passed the mixture through fine porcelain filters that trapped bacteria and fungi. The clear liquid could still make healthy tobacco leaves sick. The Dutch botanist Martinus Beijerinck dubbed it “a contagious living fluid.”
In the 1930s, the invention of powerful microscopes finally allowed scientists to see viruses. They found that viruses were unlike ordinary cells: they didn’t generate their own fuel; they didn’t grow or divide. Instead, viruses invaded cells, hijacking their biochemistry to make new copies of themselves. Being small and simple seemed like part of the viral way of life, allowing them to replicate fast.
It wasn’t until 2003 that a team of French researchers discovered the first giant virus. They had been puzzling over sphere-shaped objects that were the size of bacteria but contained no bacterial DNA. Eventually they realized that they were looking at a monstrously oversized virus, containing 979 genes.
Those first giant viruses were isolated from amoebae living in water from a cooling tower. Once scientists realized that viruses could be so large, they changed their search parameters and started finding other species in all manner of places, from swamps to rivers to contact lens fluid.
And along the way the biggest viruses got bigger. In 2011, Dr. Claverie and his colleagues set a new record with megaviruses, a type of giant virus with 1,120 genes they discovered in sea water off the coast of Chile. They then dug into the sediment below that sea water and discovered pandoravirsues, with more than twice as many genes.
Dr. Claverie speculates that pandoraviruses and other giant viruses evolved from free-living microbes that branched off from other life several billion years ago. “The type of cells they may have evolved from may have disappeared,” he said.
The idea that giant viruses represent separate branches on the tree of life is a controversial one that many other experts aren’t ready to embrace. “They provide no evidence for that notion, so it seems a distraction to me,” said T. Martin Embley, a professor of evolutionary molecular biology at Newcastle University.
Despite those reservations, Dr. Embley and other researchers hail pandoraviruses as an important discovery. “I think it’s wonderful that such crazy and divergent lifeforms continue to be discovered,” said Tom Williams, Dr. Embley’s colleague at Newcastle University.
The new study also drives home the fact that giant viruses are far from rare. Shortly after discovering pandoraviruses in sea floor sediment, Dr. Claverie and his colleagues found them in water from a lake in Australia, 10,000 miles away. “It definitely indicates that they must not be rare at all,” said Dr. Claverie.
Giant viruses may be so common, in fact, that they may be hiding inside of us, too. In a paper published online on July 2 in The Journal of Infectious Diseases, French researchers offered evidence that giant viruses dwell in healthy people. They isolated a new giant virus from blood donated by a healthy volunteer, and then found antibodies and other signs of the virus in four other donors.
Giant viruses may lurk harmlessly in our bodies, invading the amoebae we harbor. Whether they can make us sick is an open question. “I don’t believe we have the proof at the moment that these viruses could infect humans,” said Dr. Claverie.
“But again,” he added, “never say never.”
That’s wise advice when it comes to giant viruses.
Largest Viruses Ever Revealed
Even more titanic viruses might await discovery, the scientists said, and they may have features that could blur the lines between life and viruses, which are not considered to be living things.
Ten years ago, researchers accidentally discovered mimivirus, what until now was the biggest, most complex virus known. Mimivirus — a name derived from "mimicking microbes," chosen because the viruses were nearly the size of some bacteria — and its relatives the megaviruses can reach sizes of more than 700 nanometers (a nanometer is one billionth of a meter), and possess more than 1,000 genes, features typical of parasitic bacteria. Typical viruses are maybe 20 to 300 nanometers large, and many viruses, such as influenza or HIV, get along very well with 10 or fewer genes.
Now the research team that discovered those giant viruses have unearthed two more that are even bigger. The shape of these new viruses, which resemble ancient Greek jars, reminded the scientists of the myth of Pandora's box, giving the germs their name — pandoraviruses.
"The opening of the box will definitively break the foundations of what we thought viruses were," researcher Chantal Abergel, research director at the French National Center for Scientific Research in Marseille, told LiveScience.
The new record-breaking viruses are visible with a traditional light microscope, being a full micrometer or millionth of a meter in size, or approximately a hundredth the width of a human hair. They also each possess a whopping roughly 2,500 genes.
"We were prepared to find new viruses in the 1,000-gene range, but not to more than double that figure," Abergel said. "This really indicates than we don't know what are the possible limits anymore."
Megaviruses, which initially were mistaken for bacteria, were discovered in amoebas, and the investigators found pandoraviruses by also looking at amoebas. One virus, named Pandoravirus salinus, was unearthed at the mouth of the Tunquen River off the coast of central Chile, while the other, called Pandoravirus dulcis, dwelled at the bottom of a shallow freshwater pond near Melbourne, Australia. (Pandoravirus-like particles were actually first observed about 13 years ago, but were not recognized as viruses at the time.)
Two to four hours after amoebas engulf these pandoraviruses, the nucleus of the amoebas begins transforming radically, ultimately vanishing. When the amoebas finally die, they each unleash about 100 pandoraviruses. [Tiny Grandeur: Stunning Photos of the Very Small]
The amoebas the researchers used in their experiments are probably not the natural hosts for these viruses; rather, the main targets of these viruses may be protozoa or algae that are typically very difficult to grow and maintain in labs.
The scientists used amoebas instead because they can grow in labs, and gorge on their surroundings in a very indiscriminate way, sweeping most anything into themselves as they look for potential food. "This is why they are a very good target for capturing giant viruses," Abergel said.
More than 93 percent of pandoravirus genes resemble nothing known. This makes their origins a mystery — analysis of their genomes suggests pandoraviruses are not related to any known virus family.
"These viruses have more than 2,000 new genes coding for proteins and enzymes that do unknown things," Abergel said. "Elucidating their biochemical and regulatory functions might be of tremendous interest for biotech and biomedical applications. We want to propose a full large-scale functional genomics project on the pandoravirus genomes."
The fact that pandoraviruses are totally different from the previously known family of giant viruses may suggest even more families of giant viruses remain to be discovered, said researcher Jean-Michel Claverie, head of the Structural and Genomic Information Laboratory in Marseille, France.
"Our knowledge of the microbial biodiversity on this planet is still very partial," Claverie said. "Huge discoveries remain to be made at the most fundamental level that may change our present scenario about the origin of life and its evolution."
It remains a mystery why pandoraviruses have more than 2,500 genes while most viruseshave far less, the researchers said. One controversial suggestion the researchers make is that giant viruses and other viruses that depend on DNA as their genetic material may be the shrunken descendants of living, cellular ancestors.
"Parasites of any kind are submitted to the universal process of 'genome reduction' — that is, they may lose genes without harm, because the host can always provide the missing function," Claverie said. DNA viruses small and giant may all have degenerated from the same or similar cellular ancestors, "but only differ by the rate by which they lost genes from the starting ancestral genome," he said.
Future research could turn up "even more intermediary life forms between viruses and cells, establishing a continuity between the two," Abergel said. "How should we define the boundaries between cells and viruses?"
The scientists detailed their findings in the July 19 issue of the journal Science.
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