“There is a cult of ignorance in
the United States, and there always has been. The strain of
anti-intellectualism has been a constant thread winding its way through our
political and cultural life, nurtured by the false notion that democracy means
that 'my ignorance is just as good as your knowledge.'”
—Isaac
Asimov
Years
ago, I had an idea to put a blog together to discuss some of the interesting
stories from the field in which I work, Microbiology. More specifically, there
is a gap between the scientific community and the public at large that has been
growing wider and wider as time has passed. This gap is incredibly damaging,
and has played a fundamental role in allowing a number of current health crises
(the anti-vaccination movement leading to a resurgence of measles, over- and inappropriate-use
of antibiotics leading to the development of strains of bacteria that are
resistant to all of the drugs we would use to treat them, etc. etc.) The
reasons for the creation of the gap are numerous, stemming from the quote I
placed above, to the failure of science media to convey the findings of
research to the public in a meaningful way, to the all-too-frequent ease with
which researchers have dismissed the need for public relations with their work.
This is a growing problem, and one that worries me personally. I can’t do my
part to fix this from the lab bench, however. I’m hoping I can do my part
through MicrobeReel.
My goal
with this blog is to present new and interesting research in Microbiology in a
way that is understandable and approachable to folks like you, the laymen. I
want this to be a resource for readers to learn about the honestly amazing and
miraculous advancements science is making EVERY DAY in the fight against microbes.
I’ll keep my eyes out for the interesting stuff, and I’ll do what I can to
break them down and make them easier for those who haven’t spent decades
learning enough jargon to understand them. I hope I succeed, and I hope you’ll
join me in the effort.
***
In a
way, I picked the subject of this post because it combines what will likely be the two
stars of the show for MicrobeReel: bacteria and viruses. More specifically,
the paper I’m presenting represents a novel mechanism by which certain species
of viruses can jump onto the outside of bacteria in our gut and
use them as a vehicle to deliver them to the cells they want to infect as a
group, rather than individually. By doing so, they solve an underappreciated
problem that many viruses routinely face.
We’re
used to thinking of a living thing’s genetic material being pretty stable.
Mutations, for the most part, are a bad thing for organisms like us. Four and a
half billion years of evolution have slowly directed the development of traits
to work in the optimal way for us, and most of the time it’s bad if something
causes the way those traits are expressed to change. For viruses, particulary
viruses that use a different sort of genetic material called RNA (as opposed to
our DNA), a healthy amount of variation is actually critical for their
survival. They’re caught in a constant arms race between viral infection and
the immune system of their hosts, with the stakes being their ability to
survive and reproduce themselves. One of the best ways to win that race is
to change themselves faster than the immune system can adapt, by having a much higher mutation rate than that seen in DNA-based organisms. In some
viruses, this even leads them to develop what scientists refer to as a “quasispecies,”
where trying to describe the HIV viruses infecting a certain individual as one
type of virus is technically inaccurate, since the patient is actually infected
with a cloud of mutants that all differ in slight ways from each other. This is
also one of the reasons why eradicating diseases like AIDS, flu, or the common
cold is so difficult: by the time you’ve made a drug that’s effective against
one strain, you find out that it doesn’t work against a different one and,
usually, the strain it DID work against evolves rapidly to get become
resistant. It’s a pain in the butt for virologists and drug companies, but it
also carries a cost.
The same
rules about the danger of mutation apply to viruses as us: their genes have
gone through a lot of rounds of evolution to become the optimized versions of
themselves that they can be. Introducing mutations into a “perfect” gene can end up making them much less efficient or even totally non-functional, and
for a virus there is no way to test and make sure your genes work before you’re
trying to infect a cell. You’re made. You’re packaged. You’re released. And
when you get to a new host cell, the proteins you need to initiate an infection
either work or they don’t. One of the theoretical methods by which viruses get
around this is called superinfection. Put simply, two different virus particles
get into the same cell and, before they move on to initiate the full infection, there’s
a chance they get together and swap some of their genetic material back and
forth through a process called recombination. Through recombination, two virus
particles with defective or suboptimal mutations have a chance to correct their
errors by exchanging for non-mutated copies. This presumably happens relatively frequently in a
host that’s well into their infection, as they’re full of virus. But what about
when the virus finds a new host and has to establish a new infection?
Well,
the answer is that a lot of the time these mutants just don’t work. One of the
little known facts about HIV is that it’s actually not very efficient at infecting
new hosts. The minimum infectious dose (how many particles you may have to be
exposed to in order to actually get the disease) for HIV ranges wildly, but is
estimated to be as high as 65,000 copies of the virus(1)!
The reason is this: a lot of the HIV virus particles in an
infected person have mutated to the point that they really aren’t that good at
starting a new infection in a new patient (that doesn’t mean you should be
risky, though. It still only takes one incredibly lucky virus particle to give
you AIDs. Practice safe sex and don't share needles, kids!) And, because the amount of virus that gets
into the new host to establish the new infection is so much lower than it is
relative to an infected host, the opportunities for superinfection to happen by
random chance to allow for recombination is also, presumably, quite low. So how
do the viruses get over this hump?
 |
| Electron microscope images of viruses stuck to the outside of various bacteria. |
An open
access paper (so you can go read it for yourself, if you want.) from the
journal Cell Host & Microbe presents one potential mechanism(2).
The laboratory of Julie K Pfeiffer from the University of Texas Southwestern
Medical Center endeavored to show how viruses that infect your gut, called
enteric viruses, can grab onto the outside of the bacteria that live there and hitch a ride to a host cell. They use Poliovirus as their model enteric
virus, and they use some methods that are actually pretty straight forward,
mixing the virus strains with various types of bacteria and using a number of
assays to measure which combinations lead to increased ability to infect cells,
induce superinfection, and potentially increase the rate at which recombination
happens. Recombination can be measured by taking two strains that are both defective for replicating in one specific condition (in this case, temperature or presence of a drug called gentamycin), and seeing if they can succesfully infect cells where both of the conditions are present. The only way that can happen is for them to recombine, making a virus that can survive both selections.
 |
| Graphical schematic of how the viruses can use the bacteria to get in the cells together. © 2017 Elsevier Inc. |
The authors determined that not all species of bacteria are created equal for this task, and different virus genes can also play a role in determining their ability to stick to bacteria. Despite what you might think, bacteria that are able to
actually able to get into the cells themselves weren’t better at inducing
superinfection, suggesting that it’s more a matter of the viruses jumping onto the
outside of a bacteria and then riding to the gut cells, whereupon they hop off
and get into the cell together. By doing it in a group, this lets those
viruses concentrate themselves on infecting individual or small groups of cells
rather than scattershot throughout the whole gut tract, increasing the chance
for superinfection and, thus, giving themselves a better chance at recombining
and correcting for any mutations that may be reducing their chance to establish
a new infection. All of the work in this paper is done in cell culture rather
than in an animal (as those experiments would be MUCH more difficult and
expensive), but it at least suggests a mechanism that could end up being pretty
critical for viruses to establish new infections, particularly those of the gut
which have a flourishing population of bacteria to exploit. Learning how these
mechanisms work (and how to screw them up) could offer a whole new avenue for
the development of anti-viral treatments.
***
Thanks
for giving MicrobeReel a read. If you like it, share it and follow the blog for
future stories. See you next time!
1. Reid
S, A Juma O. 2009. Minimum infective dose of HIV for parenteral dosimetry, vol
20.
2. Erickson AK, Jesudhasan PR, Mayer
MJ, Narbad A, Winter SE, Pfeiffer JK. Bacteria
Facilitate Enteric Virus Co-infection of Mammalian Cells and Promote Genetic
Recombination. Cell Host & Microbe 23:77-88.e5.
Comments
Post a Comment