Viral Replication

Hi. It's Mr. Andersen and welcome to Biology Essentials video 35. This is on
viral replication and this is a painting of Benjamin Franklin. Benjamin Franklin was always
puzzled by things that he didn't understand and one thing he didn't understand was the
common cold and what caused it. And so this is something he wrote where he's talking about
what causes the cold. "Travelling in our severe winters I have suffered Cold sometimes to
an Extremity only short of Freezing, but this did not make me catch Cold. I have been in
the River every Evening two or three Hours for a Fortnight together, when on should suppose
I might imbibe enough of it to take Cold if Humidity could give it; but no such effect
followed." And so what he's testing is this idea that colds are caused by being cold.
And what he found, just like I did growing up is that doesn't really, that's not really
what causes cold. And so what he settled on was it was, I love the wording here, it was
"the frowzy corrupt Air from animal Sub stances, and there perspired matter from our Bodies."
And so Benjamin had settled on this idea that there was something passed between us that
causes cold. Now this was before the whole germ theory, before we even identified bacteria,
yet alone viruses. He was starting to hint at this idea of a cold. What does a cold look
like? Well we now know that a cold, or a rhinovirus is going to look like this. This is a picture
of a typical rhinovirus. It's called rhinovirus because it's going to infect this upper portion
of our respiratory tract. This is what it looks like. Inside it there's going to be
genetic material. The genetic material is injected into the cells in the upper respiratory
tract and it just hijacks them, to make copies of itself. To make more of the cold virus
which we then pass on to somebody else. Now what's interesting about rhinoviruses is that
there are actually 99 different types of rhinoviruses, so almost 100 different types of rhinoviruses.
Each of them are very different. So even though you might never get the same cold twice, there's
still a lot of colds out there and they're going to mutate as well. And so in this podcast
I am going to talk about viral replication, how viruses make copies of themselves. They
mainly do this through a cycle called the Lytic Cycle where they actually assemble the
parts of a virus. And then those will eventually leave the host cell. Two things that I'll
add to that is sometimes related viruses or viruses that are around at the same time can
actually swap genetic material. And then I want to talk about briefly about RNA viruses.
A perfect example of that is HIV and how they actually make copies of themselves. It's a
little bit different. And then finally I'll talk about this, the lysogenic cycle. So in
some viruses they'll make copies of themselves, but also they can hide out in a lysogenic
cycle where they can eventually go back to the lytic cycle. What we're finding is that
when they enter into the lysogenic cycle, especially in bacteria, you can actually change
the virulence of those bacteria. In other words you can make them more or less pathogenic
or dangerous. Now this is my kids version of the lytic cycle or how viruses make copies
of themselves. So it's not super accurate. I wish viruses looked like that, but they
don't. And so what do you need to be a virus? Well you need to have some genetic material,
DNA or RNA, you have to have something to put it in so there's usually a protein coat. And
then a lot of them will have membranes around the outside that will allow them to fuse with
a host cell better. And sometimes they'll actually take those membranes with them when
they leave. So what happens in the lytic cycle is that that virus will actually drop off
some of its DNA. That DNA will move into the nucleus where the machinery of the cell will
make a copy of it. And so this process right here is called DNA replication. So if you're
were paying attention, what did I say they drop off? Well really all they have to drop
off is the genetic material. So how do they make copies of the DNA if they're just dropping
of the genetic material? Well the cell's machinery will actually do that. Watch what happens
next. That DNA will make copies of itself called RNA. That's called transcription. So
transcription is the creation of RNA from a DNA template. And then what happens next
well each of those mRNAs will go to a ribosome where they'll actually convert the message
of the mRNA to proteins of the virus. So what do we call that? That's called translation.
And so what they're using is using the machinery of the cell to not only duplicate the DNA
but to transcribe that into mRNA and then eventually to make the proteins of the virus.
And so it's pretty insidious. And you can see why we don't call viruses alive because
they really don't have the machinery of a live cell. They're using the machinery of
a cell to actually make copies of themselves. So let me get that out of the way. What happens
next, well this is why we call it the lytic cycle. The lytic cycle, or to lyse means to
break. And so usually when the virus actually escapes it will it will lyse the cell. It
will destroy the cell and it will spread that virus out. And so what's happening is you
only get a few viruses into a few cells in your upper respiratory tract. They make millions
and millions of copies which infect cells, just like a computer virus, it grows exponentially.
Now if you're paying attention you noticed somebody else snuck in here as well. So this
guy looks a little bit different, but he happened to be inside the cell at the same time so he could
take some of his genetic material with him or some of this new genetic material. And
so we can get variation in viruses as well. Now some cells are actually, or some viruses
ares what are called RNA viruses. Or sometimes we call them retro viruses. What do they have?
Well their genetic material you can see is not DNA. It's going to be RNA. They'll also
usually have an enzyme that goes along with them. In this case they have something called
reverse transcriptase. So if you don't know what that is, let's watch what happens in
the animation. So they inject RNA and reverse transcriptase in. And what does reverse transcriptase
do? Well it does the opposite of transcription. In other words, it takes RNA and actually
makes DNA out of it. Now why is that bad? Well, there's not going to be a lot of error
checking with in there and so in RNA viruses you have mutation rates that are just crazy.
They're not scanning the DNA to make sure there are no mistakes. The RNA constantly
has mistakes. And in fact RNA viruses will actually live on the mistakes that are made
in the copying of that. So what happens in a RNA virus, same thing as in the last slide.
They'll make RNA and they'll make proteins and then eventually that leads on its way,
along with reverse transcriptase. So here's and example of a RNA virus. This is called
HIV. And so we can see in here that they've got the RNA, so they've got this genetic material
inside here, but they also have reverse transcriptase, that enzyme that looks like that. They also
have proteins around the outside. And they also have a membrane around the outside. And
so HIV is an example of a RNA virus. And what I said just a second ago is that RNA viruses
love mistakes. They love high mutation rates. And so the problem with HIV is that we can
start to make a vaccine but they'll mutate so quickly that it's not going to work. And
so RNA viruses is kind of a double edged sword. On the one side, being RNA as their genetic
material makes it harder to attack them and find medication for them. On the good side,
this reverse transcriptase has been a target that we can actually use to make most of our
anti-AIDS or anti-HIV drugs. And so it's kind of a different virus. Mutates really really
quickly, but also allows us to treat it as well. Last thing I want to talk about is the
Lysogenic Cycle, and so I've kind of walked you through this which is the lytic cycle.
That's where a virus injects its DNA. It makes copies of itself. It makes the machinery of
the virus and then eventually this would be that lysing or that release of the viruses
to go infect more cells. But there's also a different cycle and that's called the lysogenic
cycle. Lysogenic means creating lytic is the best way to think about it. It can give birth
to the lytic cycle. So what happens here is they'll inject their DNA in. It'll actually
sit in the bacteria and then as the bacteria copies itself, it'll be copied over and over
and over again. So that's pretty cool. In a lysogenic cycle, which is not in all viruses,
they're actually getting the bacteria to copy themselves over and over and over again. They
can eventually jump back into the lytic cycle and then this continues. So cold sores are
an example of that. If you have cold sores, or those big sores on the outside of your
lip, you'll have those forever. You have the DNA inside the cells inside your body. They're
sitting in the lysogenic cycle and then they can jump into the lytic cycle when your immune
system is suppressed. So it's pretty cool, at least cool from the side of the virus way
to pass themselves. But the other thing that's interesting about the lysogenic cycle is that
when bacteriophages and bacteriophages remember are going to be viruses that infect
bacteria, when they enter into the lysogenic cycle they can actually change the virulence
of the bacteria. And so cholera is an awful disease. It's a diarrheal disease, so you
die, this is a person with cholera, you die of severe dehydration. It's caused by a bacteria,
Vibrio cholerae and it's been around for thousands and thousands of years. But what we've discovered
is that cholera itself is actually not that bad. It's not very virulent. It won't give
off toxins until it's infected by this virus. And once it's infected by this specific CTX
virus then it becomes virulent and can lead to these awful cholera outbreaks. What we
find though is that natural selection is not always our enemy. And in cholera outbreaks
if we can clean up the water supply we can actually force the cholera bacteria to evolve
less tolerance, a tolerance where they don't have the phages and they can't pass them on.
So we're actually using that for good. And so that's how viruses make copies of themselves.
Remember all they have to have is a little bit of genetic material, a protein to carry
them in, maybe a membrane and then they use the machinery of us to copy themselves. And
so those are viruses and I hope that's helpful.