FBNSV is
one of several “multipartite viruses” that split their genes among different
capsules. These oddballs were first discovered in the 1940s, and though they
account for about 20 percent of known viral species, they’re still rather
obscure. Blanc thinks that’s because they almost always infect plants and
fungi, and only two have been found in animals—one in a moth and one in a
mosquito.
“I lecture on several virology courses, and even people in Ph.D. programs
haven’t heard of them,” he laments. “They’re everywhere, but because they’re
mainly on plants, no one cares.”
These viruses have always been baffling, even
to virologists who knew about them. Everyone assumed that they could only
reproduce if all the segments infected the same host cell. But the risk of
losing a piece, and so dooming the others, skyrockets as the number of pieces
goes up. In 2012, two researchers
calculated
that the odds of successfully getting every segment in the same
cell become too low with anything more than three or four segments. FBNSV, with
its
eight segments, “should never
have evolved,” Blanc says. Its mere existence suggests “that something must be
wrong in the conceptual framework of virology.”
Perhaps, he realized, these viruses don’t
actually need to unite their segments in the same host cell. “If theory was
saying that this is impossible, maybe the viruses just don’t do it,” he says.
“And once we had this stupid idea, testing it was very easy.”
His colleagues Anne Sicard and Elodie Pirolles
labeled pairs of FBNSV’s genes with molecules that glowed in different
colors—red for one segment, for example, and green for another. Then, they
simply looked down a microscope to see whether the colors overlapped in the
same cells. They almost never did. When the team first saw that, “we were
jumping and running around the lab,” Blanc says. “But we were also scared about
it being a [mistake]. We took six years to verify it.”
For example, they showed that the levels of one
segment aren’t tied to the levels of another, as you would expect if they were
replicating in the same host cell. Instead, in any one infected plant, the
different segments seem to accumulate at different rates.
But that discovery raised another problem. Each
of the eight segments carries a gene with its own vital role. One makes the
proteins that copy the virus’s DNA once it gets inside its hosts. Another
creates the proteins that form the virus’s capsules. See the problem? If these
segments end up in different cells, the DNA-copying
one shouldn’t be able to make capsules, the capsule-making gene shouldn’t be
able to copy itself, and both of them would be stuck.
That
doesn’t happen, the team discovered, because the virus’s genes might be stuck
in neighboring cells, but the proteins created by those genes can move. The
capsule-making protein can get into a cell
with the DNA-copying gene, and cover it. The DNA-making protein can get into a cell
with the capsule-making gene, and copy it. Think of the eight segments as
factories in different cities, shipping assembly robots to one another so that
each site can manufacture its own separate product. It is within this expansive
trade network that the distributed virus truly exists.
Read: The
oldest virus ever sequenced comes from a 7,000-year-old tooth
It’s not clear
how this
network operates, but many scientists have found that plant proteins can voyage
between
cells, even
over
long distances from root to shoot. Some researchers who study
multipartite viruses have
even
suggestedthat they could make use of these botanical highways. But
Blanc’s team has now found clear and unambiguous evidence that they do.
Perhaps, he says, “this is why multipartite viruses don’t exist so much in
animals. Maybe it’s harder for our proteins to travel between cells.”
“The work is very important … and very
carefully done,” says
Marilyn
Roossinck of Pennsylvania State University. For decades, she
has been studying a different multipartite virus that affects cucumbers, and
though she has seen some of the patterns that Blanc’s team did, “these were
never published, as their significance wasn’t clear,” she says.
“This report challenges a fundamental
assumption of virology,” adds
Rodrigo
Almeida of the University of California at Berkeley, who
studies plant diseases. “I am not aware of any similar example in biology,
where genetic information appears to be split among host cells.”
The closest example I can think of exists in
cicadas. These noisy insects
rely
on a bacterium called Hodgkinia,
which lives inside their cells and provides them with nutrients. But this one
bacterium has fractured into several daughter species, each of which contains
just a few of
Hodgkinia’s full set of genes. None
of these partial microbes can survive on its own; they only function as a set.
But these daughter species are all still locked within the same cell, so
they’re not truly distributed as the virus is. They are also problematic: If
any of them were to disappear, the rest would also die out, as would their
cicada host.
Hodgkinia’s fragmented existence is
a looming disaster—“a slow-motion extinction event,” according to John
McCutcheon, who described it.
By contrast, multipartite viruses are clearly
very successful, so their bizarre distributed existence must have some benefit.
And Blanc thinks he knows what that might be.
His team has shown that when FBNSV infects a
plant, the frequency of each segment is very predictable. Some of them are
common and others are rare, but their relative proportions are constant, at
least within a given species of plant. If the virus infects a different plant
species, those proportions change—to a different, but still predictable,
pattern. Blanc calls these “
genome
formulas”—ratios of genes that FBNSV uses for different hosts.
The
virus’s use of these formulas reminds Blanc of the ways in which animals and
other complex organisms adapt to different environments by tweaking the
numbers
of important genes. In very rough terms, the more copies you have,
the more effectively that gene can do its thing. But viruses are tiny entities,
whose capsules only have room for small genomes. There’s not enough space for
them to just wantonly double their gene counts.
Multipartite
viruses don’t have to. If they want to emphasize the use of a certain gene,
they just need to get the segment carrying it into more host cells. “This
lifestyle allows the virus to adjust its gene copy number without mutating,”
Blanc says. It’s as if FBNSV has found a way to have the flexibility of a much
larger and more complex genome, while still keeping the unflinching efficiency
of a virus.
These discoveries could also change our understanding of other
more traditional viruses. Influenza’s genome is split into eight segments, and
unlike FBNSV, all of these are packaged into the same capsule. Researchers
typically assume that every capsule contains the full octet, but in 2013,
Christopher Brooke of the University of Illinois showed that
90
percent of them are missing at least one segment. Influenza
virus “exists primarily as a swarm of complementation-dependent,
semi-infectious virions,” Brooke wrote.
Three years later, a different team showed that
the
same is true for the virus behind Rift Valley fever: Only a minority
contain all three of the virus’s gene segments, and most are missing one.
“Perhaps the boundary between these viruses and the multipartite ones isn’t so
clear,” Blanc says.
Many viruses also produce capsules called “
defective
interfering particles,” which … well, the clue’s in the name.
They’re defective because, for some reason, they’ve lost part of their full
genome. They’re interfering because, though they’re defective, their parent
viruses will still make copies of them, flooding the total pool of capsules
with noninfective deadbeats. “These things have been known for a century, and
they’ve long been considered as junk,” Blanc says. “But they are very
efficiently maintained in any viral infection. Maybe they can profit from the
system we have identified.”
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