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Haroldo Toro- Understanding Natural Selection Is Essential for Viral Disease Control

Haroldo Toro- Understanding Natural Selection Is Essential for Viral Disease Control


Good morning everybody. Thank you very much, Jennifer,
for inviting me here. It’s a privilege to be here. My talk will be slightly different. I would like to share with
you some thoughts about, thesises of poultry. Our laboratories at the vet school, Dr. Van Santen and I, we work on trying to produce knowledge to protect poultry so that it is still, well and it remains, the most important protein source for human consumption worldwide. Indeed, we eat a lot of
chicken and eggs in the world. There are several diseases
affecting the poultry industry. And as I said before, we try to create knowledge
to prevent these diseases. One of the most important diseases, according to this report, is Infectious Bronchitis Virus. As you see here 60%, this thing doesn’t work. But the one that says IBV, it’s Infectious Bronchitis Virus. This is the most, economically,
most important disease. And the agent is shown right there. These virus particles, which look like crown. Those are coronaviruses. Those are responsible for that disease. And today I would like to explain you why is this virus so successful. The immune system works similar as the police system in our country. If the police has a good
picture of the bandit, they will catch him very quickly. If they don’t have a good picture, it’s gonna be more difficult. The immune system exactly the same thing. When we vaccinate, we provide the immune system
with a picture of the virus. And it will be destroyed. How does this virus
escape immune responses induced by vaccination? This is what I wanted to
talk to you today about. So, it’s interesting how the immune system is really the same as the police system. Because you know we
have the border control that’s innate immune response where they just check the Visas, if you have a passport. But then you have criminal police. They will go for the terrorists. If they have a picture of them they will immediately catch them. So there are several strategies by viruses to escape the immune responses. And this is probably the
most fascinating one. There are other strategies, for example, to be extremely resistant. Then you can’t destroy the virus. Or to be transmitted from
the mother to the progeny, which happens of course
in many animal species. But changing the look of the virus is probably the most amazing. And this is what avian
influenza viruses do, and coronaviruses do. Just to understand how this works, I will try to explain something very basic that most of you know. So proteins are the most
important structural units of animals and everything, plants and bacteria and viruses. The smaller units of the
proteins are called amino acids. And the sequence of those amino acids, which will determine what
type of a protein we have, depends on the DNA. And so, if you change the sequence of the DNA, you change the amino acids, and you change the protein. Again, so, this virus is what they
do is change their face. They change that feature of them that will be recognized
by the immune system. You know, if you change your face, if you are an outlaw, you will not be found by the police. You know if the police
gets a portion of you that is very conserved among humans, like a picture of your liver, that won’t help them. It helps to find the face. That is what actually varies. And as I was saying before, if you change the amino acid sequence,
this doesn’t work either. Then you change the protein, then you have different structures. And I’m just showing you
this different phenotypes which are called different structures of the same species. In this case, peach trees. Some of you will recognize
some of these as peach trees. Some of you may not. In this virus, we have the same. But we can’t see those flowers. We just can’t. So we can’t differentiate between these two different strains
you are seeing here. IBV QX and IBV Ark. They look the same for us. So because we can’t see those differences, we do the sequencing of
some proteins of this virus. And for example, here it shows you, this is how we do it, this sequence chromatogram. We see that the first
amino acid is leucine, and the second is tyrosine, and the third is glycine. We see then that they will hae a particular shape. And this is because of
this different nucleotides having those peaks in the
sequence chromatogram. In this coronavirus, what changes is the spike, which is this corona-like structures on the envelope of the virus. Those are the ones that really change. So if we were able to look very closely, we’d be able to see differences
between these viruses. And indeed, this is a model that shows that by changing these few amino acids, shown below in the chart, in the table, changes actually the structure or the phenotype of the spike. So the police, the immune system, will not be able to recognize. By just changing a few amino acids. And the mechanism behind this was discovered long time ago when Charles Darwin
proposed a principle that the preservation of favorable variations and the rejection of injurious variations he called Natural Selection. That’s how these viruses work and every species, by the way. Trying to show you how it works for this virus. So evolution by Natural Selection can be divided into two steps. One is the generation
of genetic diversity, which is independent of selection. And the second is the selection process. The generation of genetic
diversity in bronchitis virus is by two mechanisms. One is mutations, and the second is recombination
of the genetic material. So we have a genetically
diverse population as shown in that picture. The first mechanism, mutations, happens when the enzyme is producing, it’s putting nucleotides
one after the next so that distinct amino
acids will be encoded, and the protein will look
like a particular thing. But sometimes it looks like
this machine right here, which is putting bricks in line. Sometimes that machine
will not find a brick and we will have a deletion. The protein will look then different. If the machine picks a
block instead of a brick, we’ll have a substitution. And if it picks a brick
that has a different color, it will also be a substitution. So that changes the
genetics of the population, by mutation. The second mechanism is when two different strains infect the same host cell. Then the progeny of these viruses… One will be exactly
like one parent, like A. The second will be same as
the other parent, like B. But there will be some viruses sharing features of both parents, just like in human populations. Because with combination, there’s sort of a way similar
to sexual reproduction. There will be exchange of genes. And, by the way, genetically diverse populations are the ones that are stronger. Those are the ones that
will be able to adapt to changes in the environment. This is true for this virus. Yes indeed it is. This is three different viruses that originate from the
same original viruses. Actually these are three vaccines. They all come from exactly the same virus. But as you see here in vaccine A, there is two peaks right there. So you have a major population encoding tyrosine, and a minor coding histidine. Vaccine B has only tyrosine there. And vaccine C has a
major population coding for histidine, and a minor coding for tyrosine, even though they come from
exactly the same original virus. So we have a genetically
diverse population, just like other populations. That was step one. The second step of natural selection is the actual selection process where the genetic endowment
of the few survivors during reproduction, and thus abundant new genotypes, are tested in the next generation. Individuals favored by selection will contribute genotypes to the gene pool that were apt to spread
in future generations and thus enhance adaption of
the population as a whole. So we start with a genetically
diverse population, like that one, we apply selective pressure, and we may have this result for example, that that particular
individual was more fit in the environment. Or we may have this population which is a mixed population, where two individuals were
more fit in the environment. That’s the same with other species, with all kinds of species. For example, white skin color, for example, is an adaptation to
low levels of sunlight. Because white skin will allow the sunlight to go through. And you will be able to produce vitamin D. So people living in areas where there was dark areas in the world, Norway, Finland, Northern Europe, you would be better adapted
if you have white skin. In contrast, black skin will block the sunlight. If you live in areas where
there’s lots of sunlight, you want to have black skin because then there will enough
vitamin D production in your skin cells. If you put a black person
in a low sunlight area, you will have more risk of deficiency of vitamin D. If you put a white person
in lots of sunlight, you will have skin cancer. Is this true for viruses? Here we put a virus into these chickens by eye drop. And you see, the sequence of that virus shows two pigs in the middle. One codes for serine, and the other for alanine. When we rescue this virus out
of the chickens afterwards, we find that just one
population was more fit, was more successful in that environment. It codes only for alanine. So selection works. This is why we have all
these outbreaks of disease everywhere in the world with different strains
of bronchitis virus. And the greatest
challenge for IBV vaccines is to protect against a
continuously changing target. Thank you very much for your attention. (audience clapping)

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