Viruses
Have a Secret, Altruistic Social Life
Researchers are beginning to
understand the ways in which viruses strategically manipulate and cooperate
with one another.
[[Everything
is always much more complicated than we thought.]]
Viruses might seem like the
ultimate selfish parasites to their hosts, but researchers are discovering that
they can have extensive social interactions with one another, including some
behaviors that seem like altruism.
April 15, 2019
Social organisms come in all
shapes and sizes, from the obviously gregarious ones like mammals and birds
down to the more cryptic socializers like bacteria. Evolutionary biologists
often puzzle over altruistic behaviors among them, because self-sacrificing
individuals would at first seem to be at a severe disadvantage under natural
selection. William D. Hamilton, one of the 20th century’s most prominent
evolutionary theorists, developed a mathematical theory to explain the
evolution of altruism through kin selection — for instance, why most individual
ants, bees and wasps forgo the ability to reproduce and instead pour all their
efforts into raising their siblings. Bacteriologists developed game-theory
models to explain why bacteria in groups produce metabolites for their
neighbors, even though some cheaters take advantage of the situation.
But until recently, no one had
considered that simple viruses, too, have social lives that influence their
fitness and their evolution. “From a theoretical perspective, there is clearly
huge potential for viruses to interact socially, leading to possibilities for
cooperation and conflict,” wrote Stuart West, a biologist at Oxford University who
studies the evolution of social behaviors, in an email to Quanta.
“However, there has been relatively little attempt to tackle this empirically.”
In a recent study published
in Nature Microbiology, Rafael Sanjuán, an
evolutionary geneticist at the University of Valencia in Spain, and his
colleagues used a combination of theory and experiments to explore viral
cooperation and conflict. They found that the spatial structure of a viral
infection — the way that different sets of viruses can be isolated in
separate compartments of the infected body — matters tremendously. In an
evenly mixed system, altruistic viruses fall victim to “cheaters” that take
advantage of their sacrifices, but if pockets in the body can isolate and
shelter the altruists, they have a shot at survival.
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Consider
the vesicular stomatitis virus (VSV), a less dangerous member of the same viral
family as rabies. Viral infections usually stimulate the cells of their
mammalian hosts to produce interferons, the signaling proteins that raise
neighboring cells’ antiviral defenses and interfere with viral replication. The
wild-type VSV has evolved ways to suppress its host’s innate immune system, but
at the cost of reproducing more slowly. Still, that ability enables the
population of suppressive viruses to thrive — unless a “cheater” variant comes
along.
The cheater does not have the
ability to suppress its host’s defenses; in fact, its presence stimulates the
release of interferons. But it still reaps the benefit of a lowered immune
response because of the nearby VSVs that suppress interferon release. Because
the cheaters don’t pay the reproductive cost of interferon suppression, they
can outcompete the wild-type virus in the short term. From a social behavior
standpoint, as Sanjuán and his colleagues pointed out in their paper, the
wild-type VSV’s suppression of interferon qualifies as an altruistic act
because in effect the wild type sacrifices itself for the cheater.
Eventually, the host’s interferon
response overwhelms both types of viruses and kills them. It might seem like
natural selection would therefore always weed out the ability to suppress
interferon because its altruism would perversely leave viruses that had it at a
disadvantage.
Sanjuán’s modeling study shows,
however, that is not necessarily the case: The altruistic
interferon-suppressing virus can still evolve and thrive if it and the cheater
are physically segregated. Structures and barriers in the body can create
havens where the interferon-suppressing viruses can survive, safe from the
damage that cheaters would otherwise bring down upon them.
From a theoretical perspective,
there is clearly huge potential for viruses to interact socially, leading to
possibilities for cooperation and conflict.
Stuart West
To
model the specific conditions in which innate immune suppression can occur, the
researchers used the theoretical framework that Hamilton developed. According
to Hamilton’s rule, altruism evolves when r × B > C,
where B is the benefit to the recipient, ris the
recipient’s relatedness to the giver, and C is the cost to the
giver.
The researchers also used a
parameter to indicate that the benefit, B, depends on whether a
virus is surrounded by wild-type or cheater neighbors. Applying Hamilton’s rule
to well-mixed and spatially segregated combinations of the two VSV variants,
they could empirically estimate the parameters in Hamilton’s equation.
“For innate immune suppression to
evolve, you need spatial structure,” Sanjuán said. Because both the virus and
the host’s interferon response spread out from cell to cell, it’s actually
quite difficult to avoid the emergence of spatial structures during infection.
Limitations on the rate of diffusion of viral particles and interferon
molecules, as well as physical barriers in the body’s tissues, easily create
spatial heterogeneity, thus allowing for the evolution of innate immune
suppression.
In animals with complex behaviors
and in bacteria with relatively complex communication systems, the outcomes of
evolutionary scenarios are influenced by many factors. In the case of viruses,
“it’s much simpler,” Sanjuán said. “Everything is dictated by spatial
structure. There is no other known process that can affect the outcome of the
system. If the viruses are mixed, then this altruism cannot evolve, and if they
are segregated, then the altruism can evolve.”
Another aspect of social
evolution of viruses that Sanjuán is investigating is why multiple viral
particles sometimes gather and infect a cell together. The trade-off is that,
if the viral particles assemble, there are fewer units to infect different
cells. So “in principle, this is costly because it limits diffusion
capability,” Sanjuán said. But his team found, to their surprise, that the
aggregated viruses grow faster and produce more progeny. This result was
dependent on cell type: In tumor cells that have no innate immunity, being
aggregated was costly. But in normal cells, which do mount an innate immune
response, being aggregated was beneficial for the viruses because it allows the
viruses to overwhelm the innate immune response, Sanjuán suggested.
Although the strategy of
aggregation for infection seems beneficial for the virus, it too can lead to
the evolution of cheaters. For example, if one virus in the aggregate loses a
few genes, then it can replicate more quickly, and with that advantage it can
outcompete the other viruses in the aggregate. These
gene-deficient viruses are known as defective interfering particles
(DIPs): Many of them lack about 90 percent of the viral genome and survive as
just a small piece of RNA that can replicate very quickly inside a host (they
cannot ordinarily infect a new host because they are so incomplete). In cell
cultures with a high density of viral infections, the DIPs take over and soon
represent more than 99 percent of the viral population, Sanjuán said.
The existence of DIPs may touch
on another puzzle: Do viruses adjust their manipulations of one another in
keeping with the needs of their life cycle? Raul Andino, a virologist at the University of
California at San Francisco, points out that early in its invasion of a host, a
virus might want lots of company because multiple simultaneous infections would
increase its odds of success.“But then they want to reduce the possibility of
high multiplicity of infection at a later stage, to reduce the possibility of
production of these defective particles,” he said. “This is something we don’t
fully understand, but it is a really interesting problem.”
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