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Summary Virology - introduction lectures (3)
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Samenvatting voor het vak virology - de inleiding (3 lessen)
[Meer zien]Voorbeeld 4 van de 52 pagina's
Voorbeeld 4 van de 52 pagina's
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Voorbeeld van de inhoud
VirologyAn introduc on to virology
1. What are viruses?
Most abundant biological en es on the planet
Major roles in global ecology and evolu on of the biosphere
- By infec ng other organisms, they put stress on them. If these organisms don’t have a good
defence system they will be eradicated (uitgeroeid) and they force these organisms also to
change (this has happened in the past)
E.g. Spanish invaders in America: they did not only invade but also brought some
diseases with them (like pox virus). There was no immunity in those popula ons
and the popula on got wiped out
Obligate intracellular parasites that package their genomes into ny protein/lipid par cles (a
virion)
- Obligate intracellular parasites they MUST be intracellular
- It is like a seed with a genome that will come alive when it enters a cell
All organisms on the planet harbour dis nc ve repertoires of viruses
- So all organisms on the planet have viruses that will infect them
We breathe and eat billions of virus par cles
Human DNA consists partly of ancestral viral gene c material
- Big part of our genome contains ancestral viral gene c material
- Latency: we all have viruses, we all are infected (for example with HERPES viruses as a child)
but then these viruses will go to sleep (= long-las ng infec ons)
Virus cannot reproduce on itself it always needs a host (like a bacteria or a eukaryo c cell)
- In these lectures we will not discuss bacteriophages (bacterial viruses) we will only
discuss viruses infec ng eukaryo c cells
Key difference between bacteria and viruses if we have a agar plate, a broth or something
else, bacteria will grow in there Viruses need cells to grow (cannot grow in a medium like
a bacteria)
Viruses aren’t living organisms but if it is not a living organism, why do we get sick of it? How
can it reproduce? How can it have a genome?
Astonishing number of viruses on Earth Viruses are everywhere
>1016 HIV par cles on Earth
- All the par cles have a genome that are slightly different form each other. So you have a
lot of varia on even between one sort of virus! Why is the variability important between
a specific virus? Why are not all HIV genomes basically the same? What is the benefit for
the virus? !!! survival of the fi est this way they can evade/avoid immune responses
(this is not fully correct, because the virus doesn’t do anything, it is not alive). Virus just
infects & creates a gene pool of progeny viruses with some variability in there. Depending
on the host and the circumstances you will get selec on, and the most fit variant of the
virus will be “chosen”, the one that is most adapted to infect in certain condi ons.
More viruses in a liter of sea water than people on earth
- >1030 bacteriophages in our seas (on the whole planet: >1031 bacteriophages)
- Bacteriophages are 150 nm long, which means that if you put them all from head to tail
and you align them, you have a distance of 1 hundred million light years (this is larger than
the size of the galaxy)
What’s cri cal for viruses is that they not only infect bacteria and eukaryo c cells, but they also
provide a gene pool
, = huge variability of sequences of genomic material that is present on earth which is covered
by viruses. By infec ng other cells some mes there is a recombina on event and you have
parts of that gene c material that will get inserted in the genomic material of the infected host
this drives evolu on, especially for eukaryo c cells. Our DNA consists for a big part of viral
genomic sequences that have been entered out of pre-ancestor cells million years ago. For
some of them, we know that they have an essen al func on like a memory forma on (there
is an ancient viral protein essen al), or placenta evolu on during pregnancy (where are also
viral proteins, which are cri cal).
The biomass of viruses is low but their abundance is very high and this is the gene c pool that is
important.
So viruses infect all living organism even thermophilic bacteria, plants and so on…
We all have heard about the human microbiome, but we can also speak about the human virome and
the global virome
Slide 7: list of examples of every part of the body where you have or can have viruses
The human genome contains remnants of viral gene c material
Approximately half of the human genome is made of transposable elements derived form
viruses
- transposable elements = elements within our genome that can jump around meaning that
they have some aspects of virions
For example retrotransposons are remnants of retroviruses (e.g. HIV)
- DNA-transposons: you have a sequence of DNA; these fragments can be cut out the
genome and can then be placed on the other side of the genome
These ‘muta ons’ happen randomly, and can change the func on of a protein
this helps a species to evolve, to create more variability
Viruses are small
Eukaryo c cell = 50-100 μm
Bacteria = 1-2 μm
Virus = in nanometer’s (20 – 200 nm)
An body = around 15 nm not too many an body’s can bind to a virus-par cle (
HERPES is around 200 nm, so here more an body’s can bind)
Viruses are diverse in structure
, This are all different viruses that can infect humans or animals & they are all to scale
Some of them are circular, some of them are pleomorphic
You can have a bullet shaped virus like rabies or you have viruses like a mini snake = filoviruses
= thread-forming viruses
Some are quite organised, other are less organised
Some are very small, some are very big
A lot of variability
Mimivirus and pandoravirus – unusually large viruses infec ng amoebae (we will not discuss them
any further, because they are not interes ng for eukaryo c cells)
All viruses are obligatory parasites (they need to get into a cell !)
found to infect each life form: archaea, bacteria, eukaryotes, plants, animals (so we have
viruses everywhere)
Viruses always have a genome, but it is not always DNA, it also can be RNA. dna or rna, ss
or ds, protein coat, +/- lipid envelope
- ds or ss DNA
- ds or ss RNA
This can be posi ve stranded, or nega ve stranded or even double stranded RNA
o Posi ve stranded: RNA has the same polarity as messenger RNA that
makes the protein this type of genome can be recognized by ribosomes
and can be directly translated into proteins
o Nega ve stranded RNA: not recognized by ribosomes (it has to change into
posi ve stranded RNA)
So all viruses have a genome (DNA or RNA, single stranded of double stranded) and all of them
have a kind of protein coat = capsid protein. Some viruses form a very nice capsule around the
genome those two together = nucleo-capsid.
- Minimal structure that all viruses consist of = genome + capsid (capsid protein is encoded
in the genome + expressed by the infected cell)
- Some viruses have an addi onal layer, consis ng of a lipid envelope (this is stolen form the
infected cell)
rely on host cell for energy produc on, for protein synthesis and for reproduc on they use
all the components from the infected cell (they use proteases, other enzymes and so on…)
All viral genomes are obligate molecular parasites that can only func on a er they replicate in
a cell
All viruses must make mRNA that can be translated by host ribosomes: they are all parasites
of the host protein synthesis machinery
- Even DNA viruses must make mRNA to make viral proteins
- Viruses are very small, but they are wonderful molecular machines, meaning they can
infect our cell highjack our cells with only 5 proteins. They can escape immunity; we have
evolve to be such complex organisms with innate/adap ve immunity, with all the
complexity and 10 thousands of protein structures and so on to act against infec ons and
s ll a simple virus with a coding capacity of 10 000 base pairs and only 3-4 proteins, can
evade all of this and can completely highjack that system
Viruses are important disease-causing agents, but not all viruses make us sick
- Many viruses are just passengers through our body (food intake, water, environment,
breathing)
- Our immune system has learned to deal with (some) viruses
, Virus replica on
So bacteria replicate by division of the mother cell; it is the same as with eukaryo c cells =
exponen al replica on
This does not happen with viruses. If you look at the hours a er infec on with the virus and
the number of infec ous virus-par cles that are produced, it will go like this
- A virus needs to bind to a cell the virus moves around (it has no flagella like bacteria), it
has no inten on to go in a specific direc on = Brownian movement = random
- We have receptors at the surface of cells some viruses have a specificity for certain
receptors and when they by random chance occur this receptor, they will bind to it (key-
lock)
- Then the will be internalized and the genome will be transported into the cell
- So 1 virus-par cle will infect the cell virus par cle will be degraded = broken down in a
controlled manner and genome will be released.
- Once the genome is released, we will get new virus par cles + some viral proteins will be
produced
- On a certain moment, all the new produced virus par cles will be released from the
infected cell
This is 1 virus life cycle
Viruses have high genome evolu on rates
Higher eukaryotes = 10-11 muta on rate = if this organisms copies the genome that only a 10-11
base pairs will be wrongly copied we have polymerases with very good copy mechanisms (!
also proofreading capacity + error correc on mechanisms) = very low muta on rate
The bigger the genome size, the more important this is
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