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summary virology
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[Meer zien]Voorbeeld 4 van de 182 pagina's
Voorbeeld 4 van de 182 pagina's
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Door: jonaswinckelmans • 2 weken geleden
Voorbeeld van de inhoud
VirologyAn introduction to virology
1. What are viruses?
• Most abundant biological entities on the planet
• Major roles in global ecology and evolution of the biosphere
- By infecting 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 populations
and the population got wiped out
• Obligate intracellular parasites that package their genomes into tiny protein/lipid particles (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 distinctive repertoires of viruses
- So all organisms on the planet have viruses that will infect them
• We breathe and eat billions of virus particles
• Human DNA consists partly of ancestral viral genetic material
- Big part of our genome contains ancestral viral genetic 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-lasting infections)
• Virus cannot reproduce on itself → it always needs a host (e.g. a bacteria or an eukaryotic cell)
- In these lectures we will not discuss bacteriophages (bacterial viruses) → we will only
discuss viruses infecting eukaryotic 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 particles on Earth
- All the particles have a genome that are slightly different form each other. So you have a
lot of variation 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 fittest → 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 selection, and the most fit variant of the
virus will be “chosen”, the one that is most adapted to infect in certain conditions.
• 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 critical for viruses is that they not only infect bacteria and eukaryotic 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 infecting other cells sometimes there is a recombination event and you have
parts of that genetic material that will get inserted in the genomic material of the infected host
→ this drives evolution, especially for eukaryotic 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 essential function like a memory formation (there
is an ancient viral protein essential), or placenta evolution during pregnancy (where are also
viral proteins, which are critical).
The biomass of viruses is low but their abundance is very high and this is the genetic 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 genetic 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 ‘mutations’ happen randomly, and can change the function of a protein →
this helps a species to evolve, to create more variability
Viruses are small
• Eukaryotic cell = 50-100 μm
• Bacteria = 1-2 μm
• Virus = in nanometer’s (20 – 200 nm)
→ Antibody = around 15 nm → not too many antibody’s can bind to a virus-particle (→
HERPES is around 200 nm, so here more antibody’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 → infecting amoebae (we will not discuss them
any further, because they are not interesting for eukaryotic 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 positive stranded, or negative stranded or even double stranded RNA
o Positive 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 Negative stranded RNA: not recognized by ribosomes (it has to change into
positive 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 additional layer, consisting of a lipid envelope (this is stolen from
the infected cell)
• rely on host cell for energy production, for protein synthesis and for reproduction → 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 function after 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 cells, highjack our cells with only 5 proteins. They can escape immunity; we
have evolve to be such complex organisms with innate/adaptive immunity, with all the
complexity and 10 thousands of protein structures and so on to act against infections
and still 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 replication
• So bacteria replicate by division of the mother cell; it is the same as with eukaryotic cells =
exponential replication
• This does not happen with viruses. If you look at the hours after infection with the virus and
the number of infectious virus-particles 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 intention to go in a specific direction = 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-particle will infect the cell → virus particle will be degraded = broken down
in a controlled manner and genome will be released.
- Once the genome is released, we will get new virus particles + some viral proteins will
be produced
- On a certain moment, all the new produced virus particles will be released from the
infected cell
→ This is 1 virus life cycle
Viruses have high genome evolution rates
• Higher eukaryotes = 10-11 mutation 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 correction mechanisms) = very low mutation rate
→ The bigger the genome size, the more important this is
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