VIROLOGY
CHAPTER 1: AN INTRODUCTION TO VIROLOGY
1 What are viruses? Where do they originate? (ppt 1/3)
1.1 Introduction
What are viruses?
• Most abundant biological entities on the planet
• Major roles in global ecology & evolution of the biosphere
• Obligate intracellular parasites that package their genomes into tiny protein/lipid particles
• All organisms on the planet harbour distinctive repertoires of viruses
• We breathe & eat billions of virus particles
• Human DNA consists partly of ancestral viral genetic material (transposable elements: ancestral viral material)
• A lot of viruses have a zoological background & comes over to humans
Astonishing number of viruses on earth:
• > 1016 HIV particles on Earth
• Viruses on plants, in oceans, on animals, in hot water, …
• More viruses in 1l sea water than people on earth à most abundant organisms
• In biomass: a very small part à viruses are minimal structures.
• > 1030 bacteriophages (living on bacteria) in our seas
The human microbiome:
• Bacteria are living on our skins & in major organ systems
• Bacteria: also covered by viruses (= virome) à viruses that feed on bacteria = bacteriophages
• The human virome and the global virome: each anatomical system mapped out which viruses are where and
which ones cause diseases à minimal fractur of viruses infect humans, only a fraction leads to disease.
The human genome contains remnants of viral genetic material:
• Bacteria regulate processes in our body, another layer keeps control of these bacteria: bacteriophages.
• A lot of our own human genome is ancestral viral genetic material
• Only 1,5% of human genome are protein coding genes à a lot of transposable items had relics of ancestral
viruses (functions at this moment is unknown)
Viruses are small:
• Bacteria: with light microscope
• Virus: at the edge of what we can see with the light microscope à
better visible with electron microscope
• Effect of virus on cell is visible
• Different microscopical approaches can be used (angstrom level)
• Mimivirus (400nm) & pandoravirus (1000nm): unusually large viruses:
o Recently discovered
o Approach the size of bacteria
o They live on amoeba à first thought they were bacteria, but not the typical build/organistaion of bacteria
o Pandora has a ‘mouth’ that it uses to attack the cell & release genome in the cell
o They have dsDNA
1
,Viruses are diverse in structure:
• Many particles are spherical = round shapes à can package a
lot of material in a round structure
• Other structures are more complex:
o Bullet shape
o Philomentous viruses
o Variola & pox viruses: more complex structures
Viruses are obligatory parasites:
• Found to infect each life form: plants, animals, eukaryotes, bacteria
• DNA or RNA, ss or ds, protein coat, with or without lipid envelope
• Rely on host cell for energy production, protein synthesis & reproduction
• All viral genomes are obligate molecular parasites à can only function after
replicating in a cell
• All viruses must make mRNA that can be translated by host ribosomes à they are
parasites of the host protein synthesis machinery
• Virion = infectious viral particle à must fuse the membrane of the virus with cellular membrane à release
genetic material in the cell à must be compatible with the protein synthesis machinery à new viral particle
that has to be released from the cell.
• Viruses are important disease-causing agents, but not all viruses make us sick
o Many viruses are just passengers through our body (food intake, breathing)
o Our immune system has learned to deal with (some) viruses
Virus replication:
• Not comparable to bacterial replication = binairy fision.
• Look at the timeline of replication cycle: virus attaches to the cell
à virus goes silent: no trace of any virus à replicate, make
protein material in the cell à burst phase: one cell produces a
lot of virus particals à often the cells will die because they
release a huge amount of virus particals.
Viruses have high genome evolution rates:
• Viruses evolve rapidly à for example corona virus: there are a lot
of variants (alpha, beta, delta, gamma, omicron)
• Eukaryotes: large genomes, so a lot of energy needed for copying
this without mistakes à exact copy of genetic material is required
• RNA viruses: smaller genome
• All viruses typically have higher mutation rates than bacteria à
they have no proofreading à lot of mistakes
• Coronavirus is an RNA virus with largest genome we know (30kb)
(RNA molecules can tolerate a max. of 30 kb genome)
• HIV: virus that is divers à accumulates a lot of mutations over its lifetime à every time a mutation is
incorporated à a variant arises à large diversity of variants that exist in 1 patient
2
,1.2 Are viruses dead or alive?
• Comparison of cellular and viral traits:
• Cells that we see today have old membranes, carried over by mother cells during cell division à viruses don’t
have this common structure that is inherited
• Most important reasons to exclude viruses from the tree of life
o Viruses are more dead than alive:
§ Viruses lack any form of energy, carbon metabolism & cannot replicate/evolve by themselves
§ They are reproduced only within cells & they also evolve within cells à they are cell depended
§ Without cells, viruses are ‘inanimate complex organic matter’
o There are no ancestral viral lineages:
§ No single gene has been identified that is shared by all viruses
§ There are common protein motifs in viral capsids, but these have likely come about through
convergent evolution or horizontal gene transfer
o Viruses don’t have a structure derived from a common ancestor:
§ Cells obtain membranes from other cells during cell division
§ According to this concept of ‘membrane heredity’, today’s cells have inherited membranes
from the first cells that evolved & provides evidence that cells are derived from a common
ancestor à viruses have no such inherited structure.
1.3 Origin of viruses
Three traditional scenarios:
• ‘Primordial virus world’ or ‘virus early’ hypothesis:
Viruses are direct descendants of the first replicons that existed during the pre-cellular stage of the evolution
of life. Cells (protocells) did not exist yet, replicate system was able to make copies. Not with formal structure
that contained these processes.
• ‘Reductive virus origin’ or ‘regression’ hypothesis:
Viruses are the ultimate products of degeneration of ancestral cells that lost their autonomy and transitioned
to obligate intracellular parasitism (e.g. giant viruses). During the early cell life, some split of as viruses. This
theory became a thing again when large viruses were found.
3
, • ‘Escaped genes’ hypothesis:
Viruses evolved on multiple, independent occasions in different cellular organisms from host genes that
acquired the capacity for (quasi)autonomous, selfish replication and infectivity. Modern cells that have
evolved and for which specific set of genes split of in particles.
à truth: probably a combination of these 3!
A typical virus genome:
• ss or ds RNA, ss or ds DNA
• Two core modules that consist of genes encoding proteins required for genome replication (non-structural
proteins) and proteins involved in virion formation (structural proteins)
A chimeric origin of viruses:
• The replication machinery might have arisen from the
primordial pool of genetic elements (old replicon
systems)
• The structural proteins may have been acquired from
hosts at different stages of evolution (already developed)
Five hallmark viral replication genes:
• Viruses don’t have specific genes that classifies them as viruses (unlike mammalians/humans)
• No close homologues in cellular life, but shared by diverse viruses
• Links viruses with different nucleic acid types & non-viral mobile genetic elements
• RdRp (RNA-dependent RNA polymerase) universally conserved across all RNA viruses à needed for replication
and translation
o RNA recognition motif (RRM) = 1 of the most common RNA-binding domains à occurs in all forms of
cellular life à structurally related domains are widespread in many viruses & mobile genetic elements
• DNA viruses have different DNA-dependent DNA polymerases
• Retroviruses have reverse transcriptase
4
CHAPTER 1: AN INTRODUCTION TO VIROLOGY
1 What are viruses? Where do they originate? (ppt 1/3)
1.1 Introduction
What are viruses?
• Most abundant biological entities on the planet
• Major roles in global ecology & evolution of the biosphere
• Obligate intracellular parasites that package their genomes into tiny protein/lipid particles
• All organisms on the planet harbour distinctive repertoires of viruses
• We breathe & eat billions of virus particles
• Human DNA consists partly of ancestral viral genetic material (transposable elements: ancestral viral material)
• A lot of viruses have a zoological background & comes over to humans
Astonishing number of viruses on earth:
• > 1016 HIV particles on Earth
• Viruses on plants, in oceans, on animals, in hot water, …
• More viruses in 1l sea water than people on earth à most abundant organisms
• In biomass: a very small part à viruses are minimal structures.
• > 1030 bacteriophages (living on bacteria) in our seas
The human microbiome:
• Bacteria are living on our skins & in major organ systems
• Bacteria: also covered by viruses (= virome) à viruses that feed on bacteria = bacteriophages
• The human virome and the global virome: each anatomical system mapped out which viruses are where and
which ones cause diseases à minimal fractur of viruses infect humans, only a fraction leads to disease.
The human genome contains remnants of viral genetic material:
• Bacteria regulate processes in our body, another layer keeps control of these bacteria: bacteriophages.
• A lot of our own human genome is ancestral viral genetic material
• Only 1,5% of human genome are protein coding genes à a lot of transposable items had relics of ancestral
viruses (functions at this moment is unknown)
Viruses are small:
• Bacteria: with light microscope
• Virus: at the edge of what we can see with the light microscope à
better visible with electron microscope
• Effect of virus on cell is visible
• Different microscopical approaches can be used (angstrom level)
• Mimivirus (400nm) & pandoravirus (1000nm): unusually large viruses:
o Recently discovered
o Approach the size of bacteria
o They live on amoeba à first thought they were bacteria, but not the typical build/organistaion of bacteria
o Pandora has a ‘mouth’ that it uses to attack the cell & release genome in the cell
o They have dsDNA
1
,Viruses are diverse in structure:
• Many particles are spherical = round shapes à can package a
lot of material in a round structure
• Other structures are more complex:
o Bullet shape
o Philomentous viruses
o Variola & pox viruses: more complex structures
Viruses are obligatory parasites:
• Found to infect each life form: plants, animals, eukaryotes, bacteria
• DNA or RNA, ss or ds, protein coat, with or without lipid envelope
• Rely on host cell for energy production, protein synthesis & reproduction
• All viral genomes are obligate molecular parasites à can only function after
replicating in a cell
• All viruses must make mRNA that can be translated by host ribosomes à they are
parasites of the host protein synthesis machinery
• Virion = infectious viral particle à must fuse the membrane of the virus with cellular membrane à release
genetic material in the cell à must be compatible with the protein synthesis machinery à new viral particle
that has to be released from the cell.
• Viruses are important disease-causing agents, but not all viruses make us sick
o Many viruses are just passengers through our body (food intake, breathing)
o Our immune system has learned to deal with (some) viruses
Virus replication:
• Not comparable to bacterial replication = binairy fision.
• Look at the timeline of replication cycle: virus attaches to the cell
à virus goes silent: no trace of any virus à replicate, make
protein material in the cell à burst phase: one cell produces a
lot of virus particals à often the cells will die because they
release a huge amount of virus particals.
Viruses have high genome evolution rates:
• Viruses evolve rapidly à for example corona virus: there are a lot
of variants (alpha, beta, delta, gamma, omicron)
• Eukaryotes: large genomes, so a lot of energy needed for copying
this without mistakes à exact copy of genetic material is required
• RNA viruses: smaller genome
• All viruses typically have higher mutation rates than bacteria à
they have no proofreading à lot of mistakes
• Coronavirus is an RNA virus with largest genome we know (30kb)
(RNA molecules can tolerate a max. of 30 kb genome)
• HIV: virus that is divers à accumulates a lot of mutations over its lifetime à every time a mutation is
incorporated à a variant arises à large diversity of variants that exist in 1 patient
2
,1.2 Are viruses dead or alive?
• Comparison of cellular and viral traits:
• Cells that we see today have old membranes, carried over by mother cells during cell division à viruses don’t
have this common structure that is inherited
• Most important reasons to exclude viruses from the tree of life
o Viruses are more dead than alive:
§ Viruses lack any form of energy, carbon metabolism & cannot replicate/evolve by themselves
§ They are reproduced only within cells & they also evolve within cells à they are cell depended
§ Without cells, viruses are ‘inanimate complex organic matter’
o There are no ancestral viral lineages:
§ No single gene has been identified that is shared by all viruses
§ There are common protein motifs in viral capsids, but these have likely come about through
convergent evolution or horizontal gene transfer
o Viruses don’t have a structure derived from a common ancestor:
§ Cells obtain membranes from other cells during cell division
§ According to this concept of ‘membrane heredity’, today’s cells have inherited membranes
from the first cells that evolved & provides evidence that cells are derived from a common
ancestor à viruses have no such inherited structure.
1.3 Origin of viruses
Three traditional scenarios:
• ‘Primordial virus world’ or ‘virus early’ hypothesis:
Viruses are direct descendants of the first replicons that existed during the pre-cellular stage of the evolution
of life. Cells (protocells) did not exist yet, replicate system was able to make copies. Not with formal structure
that contained these processes.
• ‘Reductive virus origin’ or ‘regression’ hypothesis:
Viruses are the ultimate products of degeneration of ancestral cells that lost their autonomy and transitioned
to obligate intracellular parasitism (e.g. giant viruses). During the early cell life, some split of as viruses. This
theory became a thing again when large viruses were found.
3
, • ‘Escaped genes’ hypothesis:
Viruses evolved on multiple, independent occasions in different cellular organisms from host genes that
acquired the capacity for (quasi)autonomous, selfish replication and infectivity. Modern cells that have
evolved and for which specific set of genes split of in particles.
à truth: probably a combination of these 3!
A typical virus genome:
• ss or ds RNA, ss or ds DNA
• Two core modules that consist of genes encoding proteins required for genome replication (non-structural
proteins) and proteins involved in virion formation (structural proteins)
A chimeric origin of viruses:
• The replication machinery might have arisen from the
primordial pool of genetic elements (old replicon
systems)
• The structural proteins may have been acquired from
hosts at different stages of evolution (already developed)
Five hallmark viral replication genes:
• Viruses don’t have specific genes that classifies them as viruses (unlike mammalians/humans)
• No close homologues in cellular life, but shared by diverse viruses
• Links viruses with different nucleic acid types & non-viral mobile genetic elements
• RdRp (RNA-dependent RNA polymerase) universally conserved across all RNA viruses à needed for replication
and translation
o RNA recognition motif (RRM) = 1 of the most common RNA-binding domains à occurs in all forms of
cellular life à structurally related domains are widespread in many viruses & mobile genetic elements
• DNA viruses have different DNA-dependent DNA polymerases
• Retroviruses have reverse transcriptase
4
