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So, we ask that you stay engaged
and participate fully today.
And with that, I just want to now go ahead
and introduce our presenter.
We have Huy Tu from
the UVM Vaccine Center.
And I'm just gonna read Huy's,
I always say you, Huy's bio.
Huy is a PHD student at the
UVM Vaccine Testing Center,
which is a division
of the Microbiology and
Molecular Genetics Department.
His research focuses on
how human develops defense and memory
against dengue and Zika infections.
These works contribute
to our understanding
of protective immunity to
these viral infections,
and can be applied to the
development of immunization
strategies against these viruses.
So, I wanna take this
opportunity to welcome Huy,
and I'm gonna stop sharing my screen,
and I'm gonna turn it over to Huy.
And I'm excited to learn
all about pandemics,
virology, and immunology.
- Let's see.
Thank you Lauren.
Hi everyone, thanks for tuning in today.
Let's see, do you see my screen?
- Yes, you just need to go
into your slide show view.
- (mumbles)
All good.
Thank you.
So I am super excited that
Lauren asked me to come back
to talk with this group
about what I study.
And many of you might
have come to the workshop
that we did in November
about how to combat infectious disease.
And I didn't plan it, but the month after,
we had an outbreak that last till today,
and so now that we are in the
middle and maybe, hopefully,
at the end of the outbreak,
I thought it would be appropriate
to talk a little bit more
about the fundamentals, the basics,
of what I study as apposed to
going too much into details
of Zika infection and that sort of things.
So today we are looking at virology,
so we're gonna go through some
basics about what a virus is,
the virology of a virus.
And then we'll move on to immunology,
which focuses on understanding
how the human body mount
a defense against infections,
and in this case, we're
dealing with a virus infection,
coronavirus.
So, the first thing I wanna
do is, there's a poll,
poll number one, and this
is not of great importance,
but this is something fun that
we always like to bring up
at any virology class
or even if you go to
a virology conference,
this is something that people
toss around quite a bit.
And the question is, is virus alive?
So, I'm not gonna go into
the details of what the correct answer is
because this is a very contentious topic
and the answer always
seems to be split between,
split 50, 50 really, if you
ask any expert in the field.
And I hope at the end
of this portion today,
you may be able to come up with an opinion
for yourself as to why
it is alive or it is not.
And if you are able to justify your answer
'cause that's really how science operate,
you give answer, you need
evidence to back up your answer.
- The poll is launched.
If for some reason you didn't see it,
'cause for some reason
not everyone can see
when we launch polls,
you can always put your
answer in the chat box.
But I'm gonna end this poll now.
And you can see that just like Huy said,
it was almost split.
Little bit more on the yes than the no.
- Awesome, so that's the
answer we usually see.
So what is a virus?
Hold on, where am I?
What is a virus?
So, here I have several images of viruses,
and some of these might
look familiar to you
and some may be not,
but these are the images
of influenza virus, so
your seasonal flu there.
The corona, which is
very popular these day,
and the reason why it's named corona
is because of all of the spikes
around the perimeters of the virus
that create the image of a crown or a halo
and that's what corona means.
And then you have the very
distinctive looking Ebola virus
which just creeps me
out every time I see it,
but it makes for a very good effect.
So viruses is classified as a micro.
What it means is it's a
tiny, tiny biological agent.
And I have a website right here,
which I'm not gonna go
into since I've got to like
switch back and forth
between different screens
and that just creates more
issue with my terrible internet.
But you can go to that website scale
and I have it at the end for you.
And I'm sure Lauren can
send out the information
to all of you.
You can see how big
the viruses is compared
to your, say you start coffee beans
and then you go to a grain of rice
and you keep zooming in and you will see,
like for example, your
skin cell is about this big
and then E. coli cell is tiny bit,
and then the virus is
even smaller than that.
So virus is one of the
smallest microbial agents
that we know of.
So one is tiny, it's a micro,
two, it's a obligate intracellular agent.
And it's a fancy term for
the virus being dependent
on the host cells.
So as with any biological creatures
the goal is to pass on
your genes, your genetics.
And it's the same with the virus.
The virus needs to pass on its gene,
even if you consider it alive or not.
It's not thinking, "I
need to pass on my gene."
That's just what it does.
So it needs to be inside a host cell
in order to pass on its gene,
it needs to be inside a
cell in order to reproduce.
And so that's why we call
it an intracellular micro.
And it's obligated to be in there.
And so that's why it's called obligates.
So those are the three items
that I wanted to talk about
when we think about what is a virus.
It's different from a bacteria
or a parasitic worm for example,
due to size and due to what
it can do inside our cells.
Many bacteria don't require
to go inside our cells
in order to reproduce.
And so let's look at
the poll number two.
So I just told you that virus needs
to be inside host cell to reproduce.
And to reproduce or to make more viruses
it's gonna need material
and then cellular machinery
to make all these new viruses.
So the question for you is,
which of these components
come from the host cell?
You have viral proteins,
which are building blocks for the virus.
You have the viral genome,
which is the genetic
material for the virus.
And some virus are covered
by a lipid membrane,
which is a fat, it's like a cell membrane.
In this case, it covers the virus.
And then D, all of these item above
are coming from the host cell.
So let me know what you think.
- I'm launching the poll.
If you see it, take it,
if not, type your answer into the chat.
- And while you're working with the poll,
I see a question,
is it possible to engineer a virus
that combats all the viruses?
Very interesting thoughts.
I don't think we can do it at this point.
Because each virus interact really,
the interaction is between
the individual virus
and the host cell.
There has been no study
to see if this one virus
can interact with another virus
because if they're by themselves,
they don't really do anything,
they're just like a flock of
genetic material and protein.
When they're in the cell,
that's a little bit tricky to study
because when one cell is
infected with one virus,
the virus is able to change
the behavior of that cell
to make it less or resistant
to further infection.
So this is something interesting
that we have not looked at.
But maybe one of you can
pursue this in the future.
So now all of the above wins out.
And I agree.
I agree, good job everyone.
Yeah, so a virus needs to be in the cell
and it needs the resources,
the material to make new viruses,
and all of those materials are
provided by the host cells.
So it's just mooching off the cells.
So now let's look at
the structure of the virus.
So here, I wanna talk
about the components,
what makes a virus.
So here is an image of the influenza virus
and you can see a gray background
and then there are a ton of little spots
on this gray background.
And if you slice this in half,
cut it in half, like
cracking open a coconut,
you see a little bit
more complexity there.
So the gray background on the
outside is now a gray layer.
That's actually a lipid layer.
It's a membrane that when
the flu virus infects a cell,
when it get released from that cell,
it takes away the lipid
layer of that host cell.
And then next we have a yellow layer,
and that's the matrix protein.
So these are usually
considered structure protein
because they form the
structure of the virus.
They are the infrastructure,
they form the support
of the viral particle.
And then in here, the coil,
what you're looking at
are genetic material.
So genetic material can
be DNA, it can be RNA.
Those are different kinds of molecules
that can carry instruction
on how to pass on this virus,
this gene.
And usually the genetic
material is packaged
with other proteins.
So they're not just loosey
loosey yet all tangled up,
they're actually organized
in a very complex way.
And this is important for the virus too,
because for example, influenza,
there are eight pieces
of the genetic material
and if you just let them flow
around and get all tangled up,
it's really difficult to
make a good infectious virus
if those eight pieces
of the genetic material
are not bundled together.
So there's a reason why
genetic material need
to be organized very, very well.
I haven't talked much about
the, so hold on that's the...
So here again, are the
component of the virus.
On the outside, you
have the lipid membrane
and the glycoprotein, which
I have not talked about.
And those glycoproteins
are the green pieces
around the virus here.
Inside you have protein and DNA or RNA.
And then some viruses, they
also travel with luggage.
So these luggages are usually
enzymes that the virus
take along with it,
and the goal is so that
when a virus infects a cell,
these enzymes can actually help kickstart
the reproduction process
a little bit early
so the virus can lay a
bit low key a little bit
before it recruits other cellular proteins
who come and help it make more viruses.
And there might be an advantage to that.
If you can lay low,
then it's less likely that
you're gonna get detected.
But here, the glycoprotein, I saved it
because now we're gonna
talk about the idea
of how a virus chooses a host.
What makes a virus infect that
and then another day it
can go and infect a human.
That's what usually happens
when we have a disease outbreak
like the COVID-19 right here.
So coronavirus are usually circulating
in a population of bats and
a mutation occur in the virus
and allow it to jump from one
species to another species.
And that it depends on the glycoprotein
that you're looking at here.
So if you think about
a lock and key model,
imagine the glycoprotein
on a virus as the key,
and imagine on your host cells
you have a ton of proteins
covering the surface of your cell.
And some of those proteins can be a lock
that can be unlocked by the viral key
when there's that unlock event happening,
there's a potential for an infection.
So for example the flu, this
flu right here for example,
let's call it an influenza
that will affect the human population.
This key right here can actually bind
to a receptor on the surface of your cell
and that is key-lock event
and when that happens,
the virus can infect the cell.
So that's how the virus chooses a host,
you need a compatibility
between the virus and the host.
And when it chooses a host,
where does the infection really occur?
So for example thinking
about the virus that I study,
dengue or Zika virus,
these are the viruses that
are transmitted by mosquito.
So the mosquito come
and bite me right here,
and the infection doesn't
really happen right there,
the mosquito bite will allow the virus
to go into my blood stream,
but then those viruses
don't infect the skin cell
at the bite location, they
actually infect a blood cell.
So they will travel
through my blood stream
until they see a cell that has
the lock that they can open.
So the point I'm trying to make here is
the infection is really tissue specific.
So for example, hepatitis
A or hepatitis B,
those viruses are specific to your liver,
they can only infect your
liver, the cells in your liver.
Flu infects the cells in
your respiratory tract.
HIV infects your blood cells specifically.
So that is where the infection occurs.
Let me check Q and A
to see if there's any.
Compared to say MERS, SARS
or the Spanish flu outbreak,
how serious and dangerous
is the current coronavirus pandemic?
That is a good question.
And that's something that we
continue to monitor because we.
The last literature I read,
the rate of transmission
for coronavirus is not as,
let's see, not as great,
no, a little bit greater
than the seasonal flu.
I haven't really compared
it with the the Spanish flu.
It is definitely more
contagious than MERS and SARS
in the past few years.
But we have to answer
this question considering
all of the measures that
public health officials
are implementing.
We have a stay at home order
and that really dampens
the rate of transmission for COVID-19.
This is a virus that we just,
even though it's related
to the coronavirus that we
have learned about before,
this is somewhat new to us.
So I know my friends at
UVM, it might require us
to do doing the modeling work every week
to see how much COVID-19
is being transmitted
in the State of Vermont
compared to other states
and also globally.
Let me see.
Go back to my slide,
and then we're gonna go to the next slide
and then well that's happening.
I'll look at more questions.
So now we know what a virus is.
We know how it is made.
Poll number three,
it's a true and false.
And the question is, a virus
needs to be endocytosed,
big word, but what it means
is, it needs to be taken up,
it needs to be swallowed by a cell
in order for it to start replication.
Is that true or false?
And I told you before that a
virus needs to be in the cell
to replicate.
While you're polling, I'm
gonna go back to the question,
could CRISPR be used on viruses?
The short answer is yes, but
it's a very complex system.
What we can do is we can put
the genetic material of the virus
onto a bigger piece of DNA for example.
And then usually is
you can put it in a DNA of a bacteria
and then you can modify the
viral gene using that platform
and hope to be able to get
a good virus out of that.
It's easier said than done
as with anything in science.
So if you get a virus out of that,
you have to see if it behaves
the way you want it to.
So there are a way to
modify the genetics of virus
and you don't have to use CRISPR for that,
we have a lot of molecular
genetic tools that will help.
Let's see.
So let's come back
and then I'll look at the questions again.
So a virus needs to be endocytosed.
So you agree that it needs to be taken up.
That's a reasonable answer,
but really technically
some virus doesn't need
to be taken inside a cell.
Some virus can just
sit on the cell surface
and inject its genetic
material inside a cell.
And that's all it needs
to establish an infection.
So now we're gonna look
at the viral life cycle.
What happens when the
virus get inside the cell?
So here is a very nice
diagram or pictogram I found.
So here, you have the virus with its keys,
those are the yellow knobs,
and then the cells locks are
the purple proteins right here.
That's the lock and key opening up,
and that will allow the
cell to form a pouch
and that can wrap itself
up around a virus,
and that way the virus is
now pulled inside a cell.
And then what you have is
viral fusion in this assembly.
And what that means is that
the coding of the virus
is gonna open up
and when that happens, it can
release the genetic material
into the cytoplasm of the cell.
That's the word cytoplasm.
And that just means it's the
environment inside your cell.
When the viral DNA or
RNA is inside a cell,
it can be made into protein.
Protein as building blocks
to build new viruses.
And then the genetic
material is also replicated.
So at the end you're gonna
have a ton of new viral protein
and a ton of viral RNA in this case,
and those components are
gonna assemble together
and then you get an immature virus.
So this is the brief
cursor like of a new virus.
And as it travels or the
technical term is being trafficked
through the system right here
back to the surface of the cell,
and as it goes through the
system, the virus become mature.
And at the end it gets released
from the infected cell.
Some virus can mature
outside the cell too,
and by that reasoning, a lot of people say
it doesn't need to be in the cell
to become a real mature infectious virus.
It can do that outside the cell,
therefore we can consider
it a live organism.
And as you can see the immature virus
has all of these blue knobs on it
and then the pair of scissor,
imagine that's an enzyme
that will clean up all
of those blue knobs,
and now you have again, a
yellow infectious virus.
So let's recap our step there.
You have attachment, endocytosis,
uncoating, protein and genome production,
assembly and then release.
Poll number four.
So now we will, so like
stepping outside of
variety and walking into
the human system to see
how virus creates disease
in human for today.
So my question is,
disease symptoms caused
by viral infections
are the result of,
A, viral products and new virions,
virions is just another
word for virus particles.
Disease symptoms is also
caused by immune response.
That's your B.
And then C, all of the above.
- The poll's been launched.
Let's see what you think.
- So I see A.
I'm looking at your questions now and
what is your opinion on whether
a virus is alive? (laughs)
It changes.
But I am inclined all the
time to say that it is alive.
Does getting a virus change
your body DNA permanently?
Yes and no.
Some virus will get clear from your system
and you'll see no trace of it except
for an immune response
generated from that virus.
Some virus can actually integrate itself
into your genome, but
not all over your body,
only specific cell type.
And one of those virus is the chicken pox.
Chicken pox integrates its
genetic material into your cell.
And it just lays there
quietly, very low key,
and once in a while you have shingles.
All of the above is the right answer.
And I also agree with higher majority
of people choosing immune response.
And let me show you why.
Just look at this pictogram.
So what I'm showing you
is a person experiencing
a ton of symptoms.
And this is from dengue infection.
So dengue, again is a
virus transmitted by mosquitoes.
Usually dengue is in the
tropical area of the world.
And when you get dengue,
you get a very specific type
of body pain and muscle pain,
and usually it's referred to as bone break
or breakbone disease.
That just means that
you feel like your bone
has been stabbed.
You get eye pain, a lot of headache,
you get a rash all over your body.
So it's really unpleasant.
And then in severe cases,
you have hemorrhagic fever,
your lung is filled up with fluid
because your vasculature
is now compromised.
So that's dengue.
What happens to your body
when you first get infected with dengue.
So the bear that you see right
there, that's a blood cell.
This blood cell is the
target for dengue infection.
So when dengue infect this guy,
this guy is called a monocyte
and that's a type of white blood cell.
Dengue gets in,
it will make,
so what happens is
dengue gets in the cell,
it will start reproduction,
so now you have a ton of
dengue within that cell
and the cell recognizes that
and it goes into an emergency mode.
And when that happens, the
cell makes a ton proteins
and those are called cytokine.
So cytokines are just a way
for the cell to communicate
with one another.
So for example, I have dengue right here,
that's my mosquito bite,
the monocyte in this area is
now making a lot of cytokines
and these cytokines are gonna diffuse
and travel through my bloodstream
to like all over my body
and that can trigger other blood cell
to respond to that emergency.
And one way that they do that
is to make more cytokines.
So much that sometimes
people refer to that
as the cytokine storm.
It's a fun word.
It's a very fancy word to say
but it's a very serious
condition because in that stage,
your body is in constant inflammation.
You get really, really bad fever
and some people can die from that.
So the point I'm trying
to make for this slide
is that cytokines is one
way that the immune response
react to viral infection
and that might lead to the
symptoms of the disease.
Let me check Q and A.
Where does your research take place
and how long do you store,
how do you store a virus?
Viruses are stored in a freezer.
Negative 80 degree, very cold
because we know that low
temperature can preserve
the structure and the
function of the virus.
Do you see anything in
the chat box Lauren,
that I need to answer?
- No. All the questions are coming
into the Q and A as Huy said.
Good job guys.
- Bacteriophages be used in
treatment of bacteria infection.
Interesting idea.
Interesting idea.
I'm not quite sure, but I
can imagine that's possible.
But I don't think we have
that many bacteriophages.
The one that we work in the lab
usually target very common
bacteria like E. Coli,
I don't know if there's bacteriophage
for like salmonella or listeria.
But at the same time bacterial infections
aren't as common now
as they are decades ago
because we have very good sanitation
and hygiene practice these days.
Bacterial infections aren't
on the top of the list,
so they don't really
have that much attention,
which is unfortunate
because bacteria are fascinating to study.
What are some example of diseases
caused by viral infections?
I can say,
disease caused by viral infection?
So for example, dengue
causes hemorrhagic fever,
Zika infection can cause
congenital syndrome
like microcephaly, when you
see babies with like tiny head
during the Zika outbreak,
that causes that.
HIV is interesting because what it does
it weakens your immune system
and that makes you susceptible
to many other infectious diseases.
And then there's a lot,
there's the flu that cause
the seasonal flu, et cetera.
Let's move on.
And then I'm gonna go back
to more questions later.
So now we started talking
about the immune response,
which is the focus of my study.
And this is an interesting
topic and it's very complex.
But if you go to immunology class,
the first thing that you learn
is the layers of immunity
or the layers of defense that
we have to protect ourselves.
And if you can tell me,
like take a guess and
put it in the chat box
to see what you think is
the first layer of defense
that we have.
And then I think Lauren can help me.
- So some people are writing
the first layer is skin.
- Good job.
What else, what else besides skin?
- Nose hair.
- That's also a very good idea.
- Isolation.
(laughing)
- Well, the biological defense.
A few weeks back I was like,
"My nose is getting too long,
"it's getting itchy, should I trim it?"
- We got mucus and macrophage, T cells,
surface proteins and oils.
- Good.
So the first layer is
actually the physical barrier,
so your skin and your mucosa layer,
so like the fluid that you have
in your nostril, in your mouth.
And so those are the layers
that are designed by our body
to slow down the movement
of microbial pathogen.
So because think about
your booger is quite thick.
Because it's so thick bacteria
have a really hard time moving through it
to get to the cells that
they want to attack.
So that's your physical barrier.
And then when you go all the
way down to the cellular layer,
then we have two arms
of the immune system,
and the first arm is the
innate immune response.
Oh my hands are funky.
- I was gonna let you know
it's a mirror image. Sorry.
- Because I was trying to, mirror image
'cause of the same thing.
Anyway.
So the innate immune response
and the way to think about
the innate immune response
is it's natural, it's general.
So, for example, if I have
someone breaking into my house
and I'm sitting in the kitchen,
I'm gonna defend myself
by throwing whatever
I have around me at that person,
I can throw them a muffin, I
can throw my chicken at them.
So those are not really weapons.
Those are food.
The innate immune system is
like an emergency response
that we're gonna throw whatever
we have at the invader.
And in that case, we have
these cells right here,
the basophil, the
neutrophil, the eosinophil,
and you can see they have a lot of
these middle spots in them.
And what those are, are actually pockets,
I mean, packets of chemicals.
They could be the cytokines.
So when there's an invader,
B cells are gonna release those cytokines
and those chemicals into the blood stream.
And that's the innate immune response.
And sometime is strong enough
to clear the infection.
Sometimes it's not.
That's the major part of
the innate immune response.
And you have someone mention macrophages.
These are macrophages.
And the reason why
they're depicted this way
is because their job is to roam
around in your blood stream
and they take a sample
here, a sample there,
and if it happens that they
sample a bacteria or a virus,
then they will also set
up an immune response
by releasing the cytokines, et cetera.
Dendritic cells also does that,
they will also go and sample
and engulf invaders and other molecules.
But what's really cool
is when they do that,
they will chop up,
whatever they swallow,
they will digest that
and then they throw it up
and they hold those little
fragments, if you will, a virus.
So if they eat a virus, they're
gonna chop up that virus
and then they're gonna
present the viral fragments,
say "Hey, I ate this
and now I'm presenting
"the viral fragments to you."
And they are really
cool because they bridge
the innate immune system with
the adaptive immune system.
Adaptive immune system.
And the adaptive system is
consisted of these T cells,
CD4 T cells, CD8 T cells,
you usually hear about those,
you have regulatory T cells and B cells.
So these dendritic cells are gonna show
this viral fragment to
this T cell and say,
"Hey, look at this, it's
from a virus, I think."
And these T cells are gonna
recognize that fragment and say,
"Oh, that doesn't belong here.
"That must come from a viral
invader or a bacterial invader.
"So now we need to start working."
So now you see this T cell
dressed as a superhero
and what it does is it goes and it helps.
Usually they're referred
to as helper T cell
because they go and they help
and who they help is B cell.
So CD4 T cell is gonna
come and nudge B cell say,
"Hey, we have an invader, do something."
And what B cells does is that
you see all of these molecules
on the outside of the B cell?
Those are antibodies.
We've heard a lot about antibodies lately.
So antibodies are simply molecules
that can bind to the virus.
We'll talk about B cell later.
So when T cell go and activate B cell,
B cells are gonna start
releasing those antibodies.
And then you have this CD8 T cell here
who dresses as a ninja.
It is also called cytotoxic T cell.
What it does, it kills infected cells.
So when say this T cell
see this dendritic cells
with that viral fragment,
it's going to kill this dendritic cell.
The advantage of that is if
there is viral replication
happening in this dendritic cell,
then killing it will stop
the viral reproduction cycle,
therefore you will lower the
amount of virus in your system.
So before we move onto the next question,
have a good look at all
of these for a moment
while I'm looking at your questions.
Can COVID-19 end before we have a cure?
Maybe, maybe not.
It takes a long time
to come up with a cure.
There's talk about how
to safely reopen society
and that's the topic of debate.
I'm not sure.
We're doing really well
as a State to control
the transmission of the disease,
but if we are not able to
control people coming in and out
our state or in and out of the country,
then it might be a very long period before
it really goes away.
Is it possible to engineer a
virus similar to a zombie virus
that targets the brain and
disables thing like reaction
to pain and proper functioning
of the nervous system?
Very good question.
We know that some infection by parasite
can alter the brain of animal.
And I forget, forgive me for this,
but when a mouse is infected with
Toxoplasma gondii, which is a parasite,
this mouse infected will
then go seek out cat urine.
They become attracted to urine of a cat.
Why? Because this mouse is
now carrying the parasite
and this cat is going to eat this mouse
and therefore become
infected with the parasite.
And this parasite needs to be in the cat
in order to go through
its life cycle completely.
So yes, there are way to,
well, it's far-fetched,
but there may be ways you
alter how the brain function
upon an infection.
But the tricky part is to translate
what we learn in an animal
model to a human model
because we're very different
species and there's
a lot of ethical issue
regarding testing on human.
So it's a really interesting idea.
There's a lot of discussion
that should come out of it,
but to really get there,
it's gonna take a long time.
So now I'm gonna go to my next poll,
which is regarding vaccine.
So we've been talking about
getting a COVID vaccine
and the question is, which
component of the immune system
is engaged or should be engaged
to build longterm immunity
when a person is vaccinated?
So what I didn't tell you,
I think I did not tell you
is that the adaptive
immune response is engaged.
It's thought of as the memory component
when you become infected with something,
with a virus, with a bacteria.
So here, we try to build longterm
immunity with vaccination.
So, which of these components
do you want to engage
in order to build durable,
longterm immunity?
(laughs)
- The poll's been launched.
And if you for some reason don't see it
right in the chat box,
it looks like most of you
are seeing the polls today.
- So I see a question that's been there
for a little bit long.
What is the difference
between viruses and bacteria?
They are simply different organisms.
One, we know bacteria are alive.
We're still debating whether
a virus is alive or not.
Bacteria can function,
most of them can function
outside of a host cell.
Virus can't.
So those are two differences.
Size, bacteria are usually
magnitudes bigger than viruses.
Bacteria genetics is much more complex.
Bacteria genomes can have thousands
to hundred thousands of genes.
Virus genome usually
contain about handful,
you can count 10, 20 genes.
So I would say virus is
much more evolutionary
advanced compared to bacteria
because it can propagate,
it can reproduce with
very minimal instruction
where bacteria need a lot more.
So those are some of the differences.
How easy is it to engineer a virus?
Do we know of any engineered virus?
It's relatively easy to mess
with the genetics of a virus.
I'm not sure if you've
heard about a few years ago,
I forgot where it is, but a lab was able
to engineer an influenza virus
that allow it to be
super easy to aerosolize
and that causes a massive problem
because flu is transmitted through the air
and if it is so easily aerosolized
that it causes a problem.
That's an issue with engineering virus.
So that's one example.
We have the Zika and dengue
virus I'm working with,
some of those engineered as well.
So we'd go in, we modify it a
little bit to make it weaker
and we can try to use that weakened virus
as a vaccine candidate.
It still needs to be tested and all that,
but we can try to make it weaker.
So that's an example.
Let's go back.
So the poll say you need to engage all
these components to make sure
that you have good immunity.
Which I agree.
In the past, adapted immune response
is also a very good option.
For the last 60 to 100 years or so,
we always think about
immunity in terms of B cells
and the antibodies that they produce.
Only recently we also know that T cell
also does a lot of the work.
So it will be good if we can
engage both T cell and B cell,
because if you think about it,
T cell go and help B cells.
So if you can get everyone involved
that will be really good.
For the people who choose
innate immune response,
I'm not sure what your rationale is,
but some vaccine work better if you engage
the innate immune response as well.
So you need that like first
emergency status in order
to set up a really good
immune response for later on.
So if you can do anything,
then you engage B cell.
If you can like engineer your
vaccine a little bit more
then it will be good to get T cell
and innate immune
response involved as well.
Good job, everyone.
So now how does the body fight infection?
So let's go back to the scenario
where I have my blood
cell infected with dengue.
So they create a bunch of these cytokines
and then they release these
cytokines into the blood stream.
And some of these cytokines
actually come and bind
to B cells, and the B
cells now will know that,
"Oh, this is an emergency signal.
"So I need to start working."
And as I told you earlier that B cells,
its job is to make antibodies.
So now this B cell is throwing
all of these antibodies out
and these antibodies are
going to bind to the virus.
Several things can happen.
They can cover the entire
surface of the virus
and now so the keys aren't
available for the virus
to go and unlock other cells anymore.
So that's one way you win by number.
You just cover these
viruses and you gum them up
and then eventually
the virus gets degraded
by proteins and other
factors in your blood.
Another way in the case
of bacterial infection,
these antibodies can
actually bind to the bacteria
and a bunch of them are
gonna bind to the bat
and eventually set up a signal for protein
to come and put holes on the bacteria.
And when that happen, you
can't just live with holes
on your body all over,
the bacteria will die.
So that's like several
ways that antibodies
can prevent infection by
or fight the infection
by preventing these microbes
from infecting other cells.
So the point here is B
cell making antibodies.
So we've heard recently in
the past few weeks about
the antibody test for COVID-19
and the people who recover from COVID,
we think that they have
really good antibodies
that can defeat the coronavirus.
So that's why people were
asking to donate the blood.
So in the blood you can
extract the antibodies out
and use the antibodies to treat people
who are not able to fight COVID alone.
So that's one way to help combat COVID-19,
is to use antibodies.
And in our lab, we are also
working with antibodies
that can neutralize or inactivate
Zika virus or dengue virus.
And if you develop that enough,
you can use that as an injection.
So when a person has a
mosquito bite and say,
"Oh, I think I have Zika,"
you can just give them
a shot of the antibodies
and that will help clear the virus.
And that's the thing
that we're trying to do
with COVID-19 right now too.
It just takes a long time
to come up with a good
antibody against the virus.
Question.
Oh, let's go to the next slide.
So now when we think
about longterm immunity,
we think about memory.
So what I'm showing you
here is how B cells develop.
B cell is an umbrella term
for all of these cell types.
So you have the plasmablast,
which are the cells
that show up really early
after the infection.
So in COVID-19 patients,
B cell shows up between seven and 14 days.
And after that they will turn
into different cell types.
So plasmablast can become memory B cells.
So now they have a
memory against COVID-19.
And what memory B cells
do is they circulate
in the blood stream.
With all of these antibodies,
now they can recognize COVID-19.
And when the person is infected again,
we think that these
antibodies are going to bind
to the virus and then the
cell can go to work again
and they will repeat the cycle.
They become plasmablast
and then they'll make more memory B cells
and more long-lived plasma cells.
A long-lived plasma
cells are also B cells.
What they do is they go and
live in your bone marrow
and they're called long-lived
because they live for decades.
They can live for 30 years,
60 years, really long time.
And what they do is they
make antibodies again.
Antibodies are so important.
And these antibodies will then flow out
into your bloodstream and circulate
in case you have another infection.
And the antibodies can
quickly gum up the virus
and then clear the infection.
So that's how you recover.
Now before moving on, let
me look at the questions.
So I answered the zombie virus.
Recent popular Japanese
show called Cells at Work,
how accurate is it?
I haven't seen the series,
so I'm not quite sure.
Why did you wanna study viruses?
I don't quite study virus,
I study the immune response virus rather.
But the thing a lot of
people like about virus
is how transient they are
and they're very small
and they can do so much damage.
So if you can figure out what
gives them so much strength
then you maybe able to
improve our life a lot.
Someone recently read
that the first patient
was cured of HIV, how did the cure work?
I'm not familiar with the study,
but I know that we have
really good therapeutics
who have really good drugs for HIV now.
We're still working on the vaccine,
but treatment is really, really good.
And usually the way that they measure
HIV drugs effectiveness is
to see if they can detect
the virus genetics in your blood.
And so if they can't
see it in a blood test,
then it's assumed that you
have the disease under control.
There are several things
that can mess with the result
if your machine is not sensitive enough
to pick up little bit,
just like a tiny amount
of viral material, then
it will say negative,
but really there might be a little bit
that is lower than you can detect.
But to go back to your question,
usually for viral disease,
if you are able to reduce
the amount of viral
material in your blood,
then that's a positive sign.
So for example, for COVID-19,
people were arguing whether
hydroxychloroquine is effective,
and some study give the drugs and look at
how much viral genome
that they can detect.
And there have been conflicting results.
So that's one way to measure
how the drugs really work.
Loula Gage ask,
if you have had the same
sickness several times,
why isn't your body immune to it yet?
I thought that's how vaccine works.
And really that's how
vaccine is supposed to work.
The reason is why you
might not have immunity
is because viruses are
constantly changing.
It changes quite a lot.
And it's because of the
type of genetic material
that virus has, and also
because it replicates so much.
Every replication, there's
always a little bit
some amount of mistake.
When you make a copy,
making copies of genetic material,
there is always some level of mistake
and maybe that mistake
leads to the formation
of a different strain of the virus.
That's the issue with the flu virus.
It changes every year so
that you're never really
gonna get good immunity
against all seasonal flu.
And that's the reason why
right now we're trying
to work on a universal flu vaccine
so you can just get one
shot and be good for live.
But that's really hard.
The bottom line is the
virus changes so much
that it's really difficult
for the most part
to build a good vaccine
against all the virus.
So now that we've talked about vaccine,
and I want to, let's see,
ask you how long do you think it takes
to produce a vaccine or a drug?
Can we come up with a COVID vaccine before
we let everyone out of their house?
- I just launched that poll.
How long do you think it takes?
- I see 10, five to 10 years.
Reasonable but very optimistic.
- And Huy, I'm just gonna
have you watch the time.
- Okay, yep.
I see that most people
say five to 10 years.
And that's reasonable.
It really varies.
It depends on the disease type.
Do a lot of people have it?
But usually it takes about
10 to 20 years for something
to be a brute and come out
for public consumption.
And the reason for that is because
drug and vaccine development
is a very laborious process.
So what you have to do is
to have preclinical data
and these are data
performed on animal models
that are not human.
So you start with a mouse model
and then you move on to say a
rabbit model, a monkey model.
And when you show that the
drugs are safe in these animals
and they are effective,
only then can you move
the study into the human population.
And we have to be super
careful with human trial.
We start with a very small
number of participants,
just a few tens, less than 100.
And the only thing that we
wanna see here is whether
the drug or the vaccine is
safe when we give it to people.
So if it is safe, we
can move on to phase two
where we give it to several hundred people
and at this point we're
still going to need to know
that it is still safe.
And if it is safe, is it also effective?
If it is effective does
it work on 50% of people,
30% of people, 90% of people?
If the percentage is too low,
it goes back to the phase one
and you need to modify your
study or modify the drug.
But if it is safe and
effective in phase two,
you move to phase three,
several thousand people.
And so for example, the
vaccine that we are working
on right now at UVM for
dengue hemorrhagic fever,
we started that work in the 1990s.
So that's like 30 years ago
and only now it is in
phase three in Brazil,
and phase three itself is
taking five to six years
and we haven't gotten the data back yet.
And if it all goes well,
if it doesn't make the disease worse,
if it is effective, then
you move on to FDA review
and if the FDA approves it,
then you can get it made
by a manufacturing company
and you can start
selling it to the public.
So it takes a long time.
In terms of COVID-19,
it's really hard to say
that we're gonna come up with a vaccine
in a few months or a drug in a few months.
We're still operating by
very conservative numbers
trying to control the
spread of the disease
rather than hoping for
a vaccine to come out
or a doctor to come out
and cure everything.
Phase four is not really crucial,
but if you have a similar drug,
you can go to phase four and
see if this drug is better
or not as effective, then
that's a comparative study.
But if you pass phase three,
the FDA reviews it, approves it
and then you're good to go.
So I think that's the end of my talk.
Here is again to remind you the complexity
of the immune response or the cell type.
Here are the several
resources that I pulled from
when I made this PowerPoint.
So feel free to go and play around.
They have some really
interesting things to look at.
And some really nice read.
- Before we go to questions,
I'm gonna launch one last poll.
I'm just gonna ask for some
feedback from everybody
before we get to the questions.
'Cause I know some folks
might need to hop off.
So I'm gonna launch this poll.
Let us know what you think about today's
just the overall cafe,
and then we would love to
know if you learned anything.
So I'm launching that poll
and while that poll is going,
Huy can start looking at the questions
to decide what he's gonna answer next.
You also can write any
comments you want in the chat,
but it's best if you also take this poll.
I do wanna say we have
a great lineup of cafes
for the month of May and we're scheduling
some into June already.
So we'll send that link out
to you because we definitely
have some really good ones coming up.
So keep taking this poll
and then we're gonna get
to all those questions that are in there.
We know some of you will have
to jump off, so that's okay.
There's some very nice thank yous.
I'm gonna put the chat where you guys can,
I turned it off 'cause there
was too much distraction.
But if you need to say
goodbye to some people.
Huy, why don't you start with
the questions that are there?
- So would you recommend going to UVM
if someone is interested in
biotechnology and immunology
and are there lots of
research opportunities at UVM?
Absolutely, UVM is one of the
best university in our country
in terms of being in the
front line of research.
So we have research from vaccine,
my group is immunology, so
we learn a lot of vaccine,
we learn a lot about how
the human body responds
to infection and if the
vaccine is effective,
that sort of thing.
We have lots of focus specifically
on the biology of virus.
So you can like figure out
why this virus is effective
in transmitting from
one species to another.
We have a good lung program,
so biology of the lung,
we have a really big cancer center.
So there are a lot of
opportunities for research,
interesting research at UVM.
You can go from single molecule,
so study one protein and you
can go across the spectrum
to learn about translational disease
or translational science where
there's more applicability
between your research
and the patient's health.
So I do recommend UVM.
In terms of biotechnology,
I think we are a little bit behind,
but there are people
pushing for our research
to be more translational.
So we don't wanna just like
hanging out and all that,
we want our research
to have radical impact
on people's health.
So there's a push for that.
I definitely recommend UVM,
not just because I go there.
We also have a lot of funding.
UVM is, I would say we're
very well supported.
Could COVID-19 change
every year due to mutation
similar to the flu virus?
Potentially maybe.
I mean, this is the first year we have it,
I would hate to say that let's wait for it
to come back next year
to see if it has mutated.
But viruses are prone to mutation
and so there's always a
chance that it can come back
and we're not gonna be
equipped to deal with it.
Is there a way to test
drugs without using animal?
Unfortunately no.
Right now the common way
to do it, to test drugs
is to start with an animal
model because you have to make
a gradual transition from
a Petri dish to a human.
So jumping from a Petri dish
to a human is just too hasty.
So you need to go through mouse
and then eventually monkey.
I know it raises a lot of
ethical issue and financial issue
for many institutions, but
that's the best way we know.
Were there cases when a bad
vaccine got through the process?
If someone brought, the FDA turned out
to be some negative effects,
I don't think people do that intentionally
because we're dealing
with human health here
and people's wellbeing.
I don't think people,
I believe in general that people are good.
But there are vaccines
that perform really well
in small study, but in a real population
is a little bit more problematic.
One dengue vaccine, it's not
the one that we worked on,
but one that was approved
a couple of years ago,
it's now causing a lot of
problem in the Philippines.
And that's not because of
the bribery at the FDA,
it's just because we
just don't know enough
about this virus.
And from the data that we see, it works,
but in reality it doesn't work.
So that's in phase three and beyond.
And so what we need to
go back is to go back
and to modify the recommendation.
Maybe the vaccine only works well
for people from age nine to 45.
So there are cases that drugs
cause problem, even though
it looks good on paper.
Do elderberries really
improve immune system?
So I've heard, I have not tried
and I cannot attest to that.
Could COVID-19 change?
Yeah, we answered that.
Will some of these steps be rushed
due to circumstances for a vaccine?
Absolutely yes, yes.
So if it's an emergency,
you can push it through
the process rather quickly.
Can a vaccine act on
several viruses at once?
Not likely because
viruses are very different
and vaccines are very
specific to the virus
that it's designed for, so not likely.
If a plant got COVID-19,
would it be affected?
I don't think so.
COVID-19 affects cells of the lung
and plants don't have lungs.
And if it is affected, I
wouldn't know because I,
no, I don't think so.
Could we get virus from an animal?
Yes.
The coronavirus,
older versions of it is
known to come from bats
and it's transmitted
through different kinds
of intermediary animals.
So I think MERS came from bats
and then it's transmitted through camel.
SARS came from bat and
then it's transmitted
through a civet cat.
Could an animal get COVID-19?
I don't think so.
Well, COVID-19 is the name of the disease,
but an animal can
definitely get coronavirus,
but it won't manifest as a
disease like it does in human.
That's all the questions.
- That is a lot.
Can you unshare your screen
and I'm just gonna throw one
last slide up for those of you.
We still have a great
number of you still here.
So I just wanna share with you
all that are still with us,
our final,
sorry.
This is the list of upcoming cafes,
and you can see the
registration link there.
You go there and you're
gonna have to register
for each cafe separately
because we have different
Zoom links every single time.
You can see that we have
lots of other programs,
but I would love for you all
to take the time right now
in the chat to thank Huy for giving us
so much wonderful information today.
Thank you for coming and
telling us all about this.
And your graphics were
so enjoyable to look at.
Who knew that cells were
such happy little creatures.
- Thank you.
- Thank you all for joining us today
and we hope that we see you again.
Just take your mouse and you
can click End Meeting to leave.
