Viruses

Considering that I have a cold
right now, I can't imagine a

more appropriate topic to make
a video on than a virus.

And I didn't want to
make it that thick.

A virus, or viruses.

And in my opinion, viruses are,
on some level, the most

fascinating thing in
all of biology.

Because they really blur the
boundary between what is an

inanimate object and
what is life?

I mean if we look at ourselves,
or life as one of

those things that you know
it when you see it.

If you see something that,
it's born, it grows, it's

constantly changing.

Maybe it moves around.

Maybe it doesn't.

But it's metabolizing things
around itself.

It reproduces and
then it dies.

You say, hey, that's
probably life.

And in this, we throw most
things that we see-- or we

throw in, us.

We throw in bacteria.

We throw in plants.

I mean, I could-- I'm kind of
butchering the taxonomy system

here, but we tend to know
life when we see it.

But all viruses are, they're
just a bunch of genetic

information inside
of a protein.

Inside of a protein capsule.

So let me draw.

And the genetic information
can come in any form.

So it can be an RNA, it could
be DNA, it could be

single-stranded RNA,
double-stranded RNA.

Sometimes for single stranded
they'll write these two little

S's in front of it.

Let's say they are talking about
double stranded DNA,

they'll put a ds
in front of it.

But the general idea-- and
viruses can come in all of

these forms-- is that they have
some genetic information,

some chain of nucleic acids.

Either as single or double
stranded RNA or single or

double stranded DNA.

And it's just contained inside
some type of protein

structure, which is
called the capsid.

And kind of the classic
drawing is kind of an

icosahedron type
looking thing.

Let me see if I can
do justice to it.

It looks something like this.

And not all viruses have to
look exactly like this.

There's thousands of
types of viruses.

And we're really just scratching
the surface and

understanding even what viruses
are out there and all

of the different ways that they
can essentially replicate

themselves.

We'll talk more about
that in the future.

And I would suspect that pretty
much any possible way

of replication probably
does somehow exist

in the virus world.

But they really are just these
proteins, these protein

capsids, are just made up
of a bunch of little

proteins put together.

And inside they have some
genetic material, which might

be DNA or it might be RNA.

So let me draw their
genetic material.

The protein is not necessarily
transparent, but if it was,

you would see some genetic
material inside of there.

So the question is, is
this thing life?

It seems pretty inanimate.

It doesn't grow.

It doesn't change.

It doesn't metabolize things.

This thing, left to its
own devices, is just

going to sit there.

It's just going to sit there the
way a book on a table just

sits there.

It won't change anything.

But what happens is,
the debate arises.

I mean you might say, hey Sal,
when you define it that way,

just looks like a bunch of
molecules put together.

That isn't life.

But it starts to seem like life
all of a sudden when it

comes in contact with the
things that we normally

consider life.

So what viruses do, the classic
example is, a virus

will attach itself to a cell.

So let me draw this thing
a little bit smaller.

So let's say that this
is my virus.

I'll draw it as a
little hexagon.

And what it does is, it'll
attach itself to a cell.

And it could be any
type of cell.

It could be a bacteria cell, it
could be a plant cell, it

could be a human cell.

Let me draw the cell here.

Cells are usually far larger
than the virus.

In the case of cells that have
soft membranes, the virus

figures out some way
to enter it.

Sometimes it can essentially
fuse-- I don't want to

complicate the issue-- but
sometimes viruses have their

own little membranes.

And we'll talk about
in a second where

it gets their membranes.

So a virus might have its
own membrane like that.

That's around its capsid.

And then these membranes
will fuse.

And then the virus will be able
to enter into the cell.

Now, that's one method.

And another method,
and they're seldom

all the same way.

But let's say another method
would be, the virus

convinces-- just based on some
protein receptors on it, or

protein receptors on the cells--
and obviously this has

to be kind of a Trojan
horse type of thing.

The cell doesn't want viruses.

So the virus has to somehow
convince the cell that it's a

non-foreign particle.

We could do hundreds of videos
on how viruses work and it's a

continuing field of research.

But sometimes you might have a
virus that just gets consumed

by the cell.

Maybe the cell just thinks it's
something that it needs

to consume.

So the cell wraps around
it like this.

And these sides will
eventually merge.

And then the cell and the
virus will go into it.

This is called endocytosis.

I'll just talk about that.

It just brings it into
its cytoplasm.

It doesn't happen
just to viruses.

But this is one mechanism
that can enter.

And then in cases where the cell
in question-- for example

in the situation with bacteria--
if the cell has a

very hard shell-- let me
do it in a good color.

So let's say that this is
a bacteria right here.

And it has a hard shell.

The viruses don't even
enter the cell.

They just hang out outside
of the cell like this.

Not drawing to scale.

And they actually inject
their genetic material.

So there's obviously a huge--
there's a wide variety of ways

of how the viruses
get into cells.

But that's beside the point.

The interesting thing is that
they do get into the cell.

And once they do get into the
cell, they release their

genetic material
into the cell.

So their genetic material
will float around.

If their genetic material is
already in the form of RNA--

and I could imagine almost every
possibility of different

ways for viruses to work
probably do exist in nature.

We just haven't found them.

But the ones that we've already
found really do kind

of do it in every
possible way.

So if they have RNA, this RNA
can immediately start being

used to essentially-- let's
say this is the

nucleus of the cell.

That's the nucleus of the cell
and it normally has the DNA in

it like that.

Maybe I'll do the DNA in
a different color.

But DNA gets transcribed
into RNA, normally.

So normally, the cell, this a
normal working cell, the RNA

exits the nucleus, it goes to
the ribosomes, and then you

have the RNA in conjunction with
the tRNA and it produces

these proteins.

The RNA codes for different
proteins.

And I talk about that in
a different video.

So these proteins get formed and
eventually, they can form

the different structures
in a cell.

But what a virus does is it
hijacks this process here.

Hijacks this mechanism.

This RNA will essentially go and
do what the cell's own RNA

would have done.

And it starts coding for
its own proteins.

Obviously it's not
going to code for

the same things there.

And actually some of the first
proteins it codes for often

start killing the DNA and the
RNA that might otherwise

compete with it.

So it codes its own proteins.

And then those proteins start
making more viral shells.

So those proteins just start
constructing more and more

viral shells.

At the same time, this
RNA is replicating.

It's using the cell's own
mechanisms. Left to its own

devices it would
just sit there.

But once it enters into a cell
it can use all of the nice

machinery that a cell has around
to replicate itself.

And it's kind of amazing, just
the biochemistry of it.

That these RNA molecules
then find themselves

back in these capsids.

And then once there's enough
of these and the cell has

essentially all of its resources
have been depleted,

the viruses, these individual
new viruses that have

replicated themselves using all
of the cell's mechanisms,

will find some way
to exit the cell.

The most-- I don't want to
say, typical, because we

haven't even discovered all the
different types of viruses

there are-- but one that's, I
guess, talked about the most,

is when there's enough of
these, they'll release

proteins or they'll construct
proteins.

Because they don't
make their own.

That essentially cause the cell
to either kill itself or

its membrane to dissolve.

So the membrane dissolves.

And essentially the
cell lyses.

Let me write that down.

The cell lyses.

And lyses just means that
the cell's membrane just

disappears.

And then all of these guys can
emerge for themselves.

Now I talked about before that
have some of these guys, that

they have their own membrane.

So how did they get
there, these

kind of bilipid membranes?

Well some of them, what they
do is, once they replicate

inside of a cell, they exit
maybe not even killing-- they

don't have to lyse.

Everything I talk about, these
are specific ways that a virus

might work.

But viruses really kind of
explore-- well different types

of viruses do almost every
different combination you

could imagine of replicating
and coding for proteins and

escaping from cells.

Some of them just bud.

And when they bud, they
essentially, you can kind of

imagine that they push
against the cell

wall, or the membrane.

I shouldn't say cell wall.

The cell's outer membrane.

And then when they push against
it, they take some of

the membrane with them.

Until eventually the cell
will-- when this goes up

enough, this'll pop together
and it'll take some of the

membrane with it.

And you could imagine why that
would be useful thing

to have with you.

Because now that you have this
membrane, you kind of look

like this cell.

So when you want to go infect
another cell like this, you're

not going to necessarily look
like a foreign particle.

So it's a very useful way to
look like something that

you're not.

And if you don't think that this
is creepy-crawly enough,

that you're hijacking the DNA
of an organism, viruses can

actually change the
DNA an organism.

And actually one of the most
common examples is HIV virus.

Let me write that down.

HIV, which is a type of
retrovirus, which is

fascinating.

Because what they do is, so
they have RNA in them.

And when they enter into a cell,
let's say that they got

into the cell.

So it's inside of the
cell like this.

They actually bring along
with them a protein.

And every time you say, where
do they get this protein?

All of this stuff came from
a different cell.

They use some other cell's amino
acids and ribosomes and

nucleic acids and everything
to build themselves.

So any proteins that they
have in them came

from another cell.

But they bring with them, this
protein reverse transcriptase.

And the reverse transcriptase
takes their RNA and

codes it into DNA.

So its RNA to DNA.

Which when it was first
discovered was, kind of,

people always thought that you
always went from DNA to RNA,

but this kind of broke
that paradigm.

But it codes from RNA to DNA.

And if that's not bad enough,
it'll incorporate that DNA

into the DNA of the host cell.

So that DNA will incorporate
itself into the

DNA of the host cell.

Let's say the yellow is the
DNA of the host cell.

And this is its nucleus.

So it actually messes with
the genetic makeup

of what it's infecting.

And when I made the videos on
bacteria I said, hey for every

one human cell we have twenty
bacteria cells.

And they live with us and
they're useful and they're

part of us and they're 10% of
our dry mass and all of that.

But bacteria are kind of
along for the ride.

They don't change who we are.

But these retroviruses, they're
actually changing our

genetic makeup.

I mean, my genes, I take
very personally.

They define who I am.

But these guys will
actually go in and

change my genetic makeup.

And then once they're part of
the DNA, then just the natural

DNA to RNA to protein
process will code

their actual proteins.

Or their-- what they need to--
so sometimes they'll lay

dormant and do nothing.

And sometimes-- let's say
sometimes in some type of

environmental trigger,
they'll start coding

for themselves again.

And they'll start
producing more.

But they're producing it
directly from the organism's

cell's DNA.

They become part of
the organism.

I mean I can't imagine a more
intimate way to become part of

an organism than to become
part of its DNA.

I can't imagine any
other way to

actually define an organism.

And if this by itself is not
eerie enough, and just so you

know, this notion right here,
when a virus becomes part of

an organism's DNA, this
is called a provirus.

But if this isn't eerie enough,
they estimate-- so if

this infects a cell in my nose
or in my arm, as this cell

experiences mitosis, all of
its offspring-- but its

offspring are genetically
identical-- are going to have

this viral DNA.

And that might be fine,
but at least my

children won't get it.

You know, at least it won't
become part of my species.

But it doesn't have to just
infect somatic cells, it could

infect a germ cell.

So it could go into
a germ cell.

And the germ cells, we've
learned already, these are the

ones that produce gametes.

For men, that's sperm and
for women it's eggs.

But you could imagine, once
you've infected a germ cell,

once you become part of a germ
cell's DNA, then I'm passing

on that viral DNA to my
son or my daughter.

And they are going to pass
it on to their children.

And just that idea by itself
is, at least to my mind.

vaguely creepy.

And people estimate that 5-8%--
and this kind of really

blurs, it makes you think about
what we as humans really

are-- but the estimate is 5-8%
of the human genome-- so when

I talked about bacteria I just
talked about things that were

along for the ride.

But the current estimate, and
I looked up this a lot.

I found 8% someplace,
5% someplace.

It's all a guess.

I mean people are doing it based
on just looking at the

DNA and how similar it is to
DNA in other organisms. But

the estimate is 5-8% of the
human genome is from viruses,

is from ancient retroviruses
that incorporated themselves

into the human germ line.

So into the human DNA.

So these are called endogenous
retroviruses.

Which is mind blowing to me,
because it's not just saying

these things are along for the
ride or that they might help

us or hurt us.

It's saying that we are--
5-8% of our DNA

actually comes from viruses.

And this is another thing
that speaks to

just genetic variation.

Because viruses do something--
I mean this is called

horizontal transfer of DNA.

And you could imagine, as a
virus goes from one species to

the next, as it goes from
Species A to B, if it mutates

to be able to infiltrate these
cells, it might take some--

it'll take the DNA that
it already has, that

makes it, it with it.

But sometimes, when it starts
coding for some of these other

guys, so let's say that this
is a provirus right here.

Where the blue part is
the original virus.

The yellow is the organism's
historic DNA.

Sometimes when it codes, it
takes up little sections of

the other organism's DNA.

So maybe most of it was the
viral DNA, but it might have,

when it transcribed and
translated itself, it might

have taken a little bit-- or at
least when it translated or

replicated itself-- it might
take a little bit of the

organism's previous DNA.

So it's actually cutting parts
of DNA from one organism and

bringing it to another
organism.

Taking it from one member of a
species to another member of

the species.

But it can definitely
go cross-species.

So you have this idea all of
a sudden that DNA can jump

between species.

It really kind of-- I don't
know, for me it makes me

appreciate how interconnected--
as a species,

we kind of imagine that we're
by ourselves and can only

reproduce with each other and
have genetic variation within

a population.

But viruses introduce this
notion of horizontal transfer

via transduction.

Horizontal transduction is just
the idea of, look when I

replicate this virus, I might
take a little bit of the

organism that I'm freeloading
off of, I might take a little

bit of their DNA with me.

And infect that DNA into
the next organism.

So you actually have this
DNA, this jumping,

from organism to organism.

So it kind of unifies
all DNA-based life.

Which is all the life that
we know on the planet.

And if all of this isn't creepy
enough-- and actually

maybe I'll save the creepiest
part for the end.

But there's a whole-- we could
talk all about the different

classes of viruses.

But just so you're familiar with
some of the terminology,

when a virus attacks bacteria,
which they often do.

And we study these the most
because this might be a good

alternative to antibiotics.

Because viruses that attack
bacteria might-- sometimes the

bacteria is far worse for the
virus-- but these are called

bacteriaphages.

And I've already talked to you
about how they have their DNA.

But since bacteria have hard
walls, they will just inject

the DNA inside of
the bacteria.

And when you talk about DNA,
this idea of a provirus.

So when a virus lyses it
like this, this is

called the lytic cycle.

This is just some terminology
that's good to know if you're

going to take a biology
exam about this stuff.

And when the virus incorporates
it into the DNA

and lays dormant, incorporates
into the DNA of the host

organism and lays dormant for
awhile, this is called the

lysogenic cycle.

And normally, a provirus is
essentially experiencing a

lysogenic cycle in eurkaryotes,
in organisms that

have a nuclear membrane.

Normally when people talk about
the lysogenic cycle,

they're talking about viral DNA
laying dormant in the DNA

of bacteria.

Or bacteriophage DNA
laying dormant

in the DNA of bacteria.

But just to kind of give you
an idea of what this, quote

unquote, looks like,
right here.

I got these two pictures
from Wikipedia.

One is from the CDC.

These little green dots you see
right here all over the

surface, this big thing you
see here, this is a white

blood cell.

Part of the human
immune system.

This is a white blood cell.

And what you see emerging from
the surface, essentially

budding from the surface of this
white blood cell-- and

this gives you a sense
of scale too--

these are HIV-1 viruses.

And so you're familiar with the
terminology, the HIV is a

virus that infects white
blood cells.

AIDS is the syndrome you get
once your immune system is

weakened to the point.

And then many people suffer
infections that people with a

strong immune system normally
won't suffer from.

But this is creepy.

These things went inside this
huge cell, they used the

cell's own mechanism to
reproduce its own DNA or its

own RNA and these
protein capsids.

And then they bud from the cell
and take a little bit of

the membrane with it.

And they can even leave some
of their DNA behind in this

cell's own DNA.

So they really change what
the cell is all about.

This is another creepy
picture.

These are bacteriaphages.

And these show you what
I said before.

This is a bacteria right here.

This is its cell wall.

And it's hard.

So it's hard to just
emerge into it.

Or you can't just merge,
fuse membranes with it.

So they hang out on the outside
of this bacteria.

And they are essentially
injecting their genetic

material into the
bacteria itself.

And you could imagine,
just looking at the

size of these things.

I mean, this is a cell.

And it looks like a whole
planet or something.

Or this is a bacteria and these

things are so much smaller.

Roughly 1/100 of a bacteria.

And these are much less than
1/100 of this cell we're

talking about.

And they're extremely
hard to filter for.

To kind of keep out.

Because they are such,
such small particles.

If you think that these are
exotic things that exist for

things like HIV or Ebola , which
they do cause, or SARS,

you're right.

But they're also
common things.

I mean, I said at the beginning
of this video that I

have a cold.

And I have a cold because some
viruses have infected the

tissue in my nasal passage.

And they're causing me to have
a runny nose and whatnot.

And viruses also cause
the chicken pox.

They cause the herpes
simplex virus.

Causes cold sores.

So they're with us all around.

I can almost guarantee
you have some virus

with you as you speak.

They're all around you.

But it's a very

philosophically puzzling question.

Because I started with, at the
beginning, are these life?

And at first when I just showed
it to you, look they

are just this protein
with some nucleic

acid molecule in it.

And it's not doing anything.

And that doesn't look
like life to me.

It's not moving around.

It doesn't have a metabolism.

It's not eating.

It's not reproducing.

But then all of a sudden, when
you think about what it's

doing to cells and how it uses
cells to kind of reproduce.

It kind of like-- in business
terms it's asset light.

It doesn't need all of the
machinery because it can use

other people's machinery
to replicate itself.

You almost kind of want
to view it as a

smarter form of life.

Because it doesn't go through
all of the trouble of what

every other form of life has.

It makes you question what life
is, or even what we are.

Are we these things that contain
DNA or are we just

transport mechanisms
for the DNA?

And these are kind of the
more important things.

And these viral infections are
just battles between different

forms of DNA and RNA
and whatnot.

Anyway I don't want to get
too philosophical on you.

But hopefully this gives you a
good idea of what viruses are

and why they really are, in my
mind, the most fascinating

pseudo organism in
all of biology.