2024-2025 Virology
Virology
Introduction
What is a virus? Where do they originate?
What are viruses?
• Where can we find them? Everywhere
o More viruses in a liter of sea water than people on earth
o Human virome and the global virome
• Most abundant biological entities on the planet
• Major roles in global ecology and evolution of the biosphere
• All organisms on the planet harbor distinctive repertoires of viruses
• We breathe and eat billions of virus particles
• Human DNA consists partly of ancestral viral genetic material
• Obligate intracellular parasites that package their genomes in tiny protein/lipid
particles (when a virus cannot infect a cell, it will go extinct)
o Viruses are found to infect each life form: archaea, bacteria, eukaryotes,
plants and animals
o DNA or RNA, ss or ds, protein coat, +/- lipid envelope
Viruses are small and diverse in structure
• Virion = genome packed into lipid particles (‘like a seed that comes alive when
entering the cell’ = obligate intracellular)
• Viruses are small
o At the edge of what we can see with the LM: better visible with EM
o Mimivirus (400nm) and pandoravirus (1000nm) are unusually large viruses
§ Recently discovered, approach the size of a bacteria
§ They live on amoeba à they were first thought to be bacteria
§ Both dsDNA viruses
§ Pandora has a mouth used to attack the cell and release its genome in
the cell
• Latency = ‘sleeping virus’ à survival strategy. There are 2 possibilities for a virus to
be able to survive when it cannot directly infect another host:
o Be resistant (stay infectious for a very long time à not many viruses do this)
o Continuously infecting hosts with subclinical infections (you don’t even
notice you are infected so you will spread the virus) à many viruses are just
‘passengers’ and don’t cause disease because our immune system has
learned to deal with it = co-evolution.
o Long lasting/ chronic infections = latency
• Viruses provide a gene-pool
o By infecting cells, viruses will insert their genomic material in the genome of
the host, contributing to the human genome (transposable elements are
genes we have acquired from viruses; retrotransposons = from retroviruses)
1
,2024-2025 Virology
• There is variability in the genome of viruses: they have high mutation rates!
o They don’t have a DNA-repair mechanism, nor proofreading
§ Thus, most of the replication have a lot of mutation resulting in a virus
that cannot infect = junk-viruses
o This results in some viruses with high variability (e.g. coronavirus: alpha, beta,
delta, gamma, omicron)
o The variability in virus genome is important to be able to evade immune
system host (= survival of the fittest)!!!
• Viruses are important disease-causing agents, but not all viruses make us sick
o Many viruses are just passengers through our body
o Our IS has learned to deal with (some) viruses
• Viruses diaer in structure, but minimal components (very small viruses don’t fit a big
genome):
o Many particles are spherical = round shapes à can package a lot of material
in a round shape, other structures are more complex = bullet shape,
philomentous and more complex structures (variola and pox)
o Genome: DNA/RNA and ss/ds and (+) stranded /(-) stranded
o Capsid protein = capsid around genome of virus
o Capsid + genome = nucleocapsid = virion
o All viruses have capsid proteins, but not all of this form a very stable crystal-
like capsid structure!!!
o Virion + things that come to expression when a virus infects a cell = virus
à all viruses need to ‘become/make’ mRNA to make proteins; they are all
parasites of the host protein synthesis machinery
• Some viruses also have a lipid envelope
o Lipid envelope is not encoded in genome
o Lipid envelope ‘stolen’ from eukaryotic cell (membrane of cell/ ER/ GA)
o Viruses do not only rely on the host cell for their lipid envelope, but on a lot of
things: energy production, protein synthesis, reproduction
• !!! Bacteria replicate exponentially while viruses don’t!
o First viruses do Brownian movement à (bacteria
has flagella and goes in a specific direction)
o By chance the virus binds to receptor of cells
o Virus is internalized in the cell and degraded in a
controlled manner so the genome can be released.
With replication and translation, new virus particles
can be produced.
o New virus particles are released (gradually or in a burst)
• Are viruses dead/alive à dead
o They cannot produce their own energy (no carbon metabolism)
o They cannot reproduce/ evolve by themselves (obligate intracellular)
o There are no ancestral viral lineages: no single gene has been identified that is
shared by all viruses
o Viruses don’t have a structure derived from a common ancestor, like cells are
all derived from a common ancestor cell because there is ‘membrane
heridity’: during cell division, cells obtain membranes from other cells
2
,2024-2025 Virology
Origin of viruses
• There are 3 scenarios for the origin of viruses:
o Primordial virus world/ virus early hypothesis: the whole world started with
DNA floating around that could replicate
o Escaped genes hypothesis: some genes where present in ancestor cells/
bacteria and just escaped from cells, they were the products of degeneration
of ancestral cells that lost their autonomy (this theory become a thing again
when large viruses were found)
o Reductive virus origin/ regression hypothesis: viruses are remnants of a
degraded cell; it needed another cell to replicate
o Probably a combination of these three!
Di3erent kinds of genome in viruses
• dsDNA à use the DNA-polymerase of cells to replicate à proofreading à less
mutations à less variability à less chance to infect another species because of this
low mutation rate (Herpes is a dsDNA virus, thus Herpes of your cat will probably not
infect you)
• RNA-virus à uses RNA-dependent-RNA-polymerase to replicate à it is not from the
human cells since it does not exist here, so the virus encodes for it à no
proofreading à more mutations à more variability à more chance to cross
species-barrier (SARS-COV-2 is an RNA virus and thus crosses species barriers and
can cause pandemics)
o RNA viruses can be linear/circular or segmented (diaerent RNA-strands next
to each other)
o RNA-viruses don’t need a nucleus to replicate and can stay in cytoplasm
(most of them will still go in nucleus tho)
o + stranded ssRNA will be in cytoplasm (for translation) and – stranded RNA in
cytoplasm or nucleus
o Viruses don’t care about +/- stranded, they mostly are ambisense: you can
read the genome from both sides
• Genome of virus always consists of 2 core modules:
o Encodes for genome replication = non-structural proteins
§ This is used to group diaerent virus families:
• RNA-viruses
o RNA-dependent-RNA-polymerase (RdRp)
o Reverse transcriptase
• DNA-viruses
o Protein primed family B DNAP
o Rolling circle replication endonucleases
o Superfamily 3 helicase
§ The replication machinery might have arisen from the primordial pool
of genetic elements
3
, 2024-2025 Virology
§ 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 diaerent nucleic acid types & non-viral
mobile genetic elements
• RdRp (RNA-dependent RNA polymerase) universally conserved
across all RNA viruses à needed for replicationand 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 diaerent DNA-dependent DNA polymerases
• Retroviruses have reverse transcriptase
o Encodes for structural proteins (capsid)
§ Often: virus makes polyproteïns that are cut by proteases into smaller
proteins
§ Capsids have limited diversity and have the same structural backbone
in every virus = 60% of viruses have an icosahedral structure (looks like
a cristal). Other common capsid structures are rod-
shaped/filamentous or helical
§ Capsid can consist of lipid parts or proteins
§ Every virus had genes that encode for capsid. Some viruses have
genes encoding for receptor-binding proteïns (but sometimes, the
receptor binding proteins van be found on capsid proteïns)
§ The structural proteins may have been acquired from hosts at diaerent
stages of evolution à sequence and structure comparison indicate
that many capsid proteins evolved from ancestral cellular
carbohydrate-binding or nucleic acid-binding capacity and genome
protection
o Viruses can also have other genes than only these 2 core modules:
§ Regulation and timing of replication cycle
§ Modulation of host defense mechanism (this is not immune invasion
because it is not absolute: it will just block the immune response long
enough for virus to replicate)
• Genes that are not encoded in the viral genome
o The genome of viruses does not have telomeres/ centromeres like in
chromosomes
o The viral genome does not have genes encoding protein synthesis machinery
(ribosomes, tRNA)
o The viral genome does not have genes encoding for the membrane synthesis
• Chimeric origin of viruses
o The structural proteins may have been acquired from hosts at diaerent stages
of evolution
o The replication machinery might have arisen from the primordial pool of
genetic elements
4
Virology
Introduction
What is a virus? Where do they originate?
What are viruses?
• Where can we find them? Everywhere
o More viruses in a liter of sea water than people on earth
o Human virome and the global virome
• Most abundant biological entities on the planet
• Major roles in global ecology and evolution of the biosphere
• All organisms on the planet harbor distinctive repertoires of viruses
• We breathe and eat billions of virus particles
• Human DNA consists partly of ancestral viral genetic material
• Obligate intracellular parasites that package their genomes in tiny protein/lipid
particles (when a virus cannot infect a cell, it will go extinct)
o Viruses are found to infect each life form: archaea, bacteria, eukaryotes,
plants and animals
o DNA or RNA, ss or ds, protein coat, +/- lipid envelope
Viruses are small and diverse in structure
• Virion = genome packed into lipid particles (‘like a seed that comes alive when
entering the cell’ = obligate intracellular)
• Viruses are small
o At the edge of what we can see with the LM: better visible with EM
o Mimivirus (400nm) and pandoravirus (1000nm) are unusually large viruses
§ Recently discovered, approach the size of a bacteria
§ They live on amoeba à they were first thought to be bacteria
§ Both dsDNA viruses
§ Pandora has a mouth used to attack the cell and release its genome in
the cell
• Latency = ‘sleeping virus’ à survival strategy. There are 2 possibilities for a virus to
be able to survive when it cannot directly infect another host:
o Be resistant (stay infectious for a very long time à not many viruses do this)
o Continuously infecting hosts with subclinical infections (you don’t even
notice you are infected so you will spread the virus) à many viruses are just
‘passengers’ and don’t cause disease because our immune system has
learned to deal with it = co-evolution.
o Long lasting/ chronic infections = latency
• Viruses provide a gene-pool
o By infecting cells, viruses will insert their genomic material in the genome of
the host, contributing to the human genome (transposable elements are
genes we have acquired from viruses; retrotransposons = from retroviruses)
1
,2024-2025 Virology
• There is variability in the genome of viruses: they have high mutation rates!
o They don’t have a DNA-repair mechanism, nor proofreading
§ Thus, most of the replication have a lot of mutation resulting in a virus
that cannot infect = junk-viruses
o This results in some viruses with high variability (e.g. coronavirus: alpha, beta,
delta, gamma, omicron)
o The variability in virus genome is important to be able to evade immune
system host (= survival of the fittest)!!!
• Viruses are important disease-causing agents, but not all viruses make us sick
o Many viruses are just passengers through our body
o Our IS has learned to deal with (some) viruses
• Viruses diaer in structure, but minimal components (very small viruses don’t fit a big
genome):
o Many particles are spherical = round shapes à can package a lot of material
in a round shape, other structures are more complex = bullet shape,
philomentous and more complex structures (variola and pox)
o Genome: DNA/RNA and ss/ds and (+) stranded /(-) stranded
o Capsid protein = capsid around genome of virus
o Capsid + genome = nucleocapsid = virion
o All viruses have capsid proteins, but not all of this form a very stable crystal-
like capsid structure!!!
o Virion + things that come to expression when a virus infects a cell = virus
à all viruses need to ‘become/make’ mRNA to make proteins; they are all
parasites of the host protein synthesis machinery
• Some viruses also have a lipid envelope
o Lipid envelope is not encoded in genome
o Lipid envelope ‘stolen’ from eukaryotic cell (membrane of cell/ ER/ GA)
o Viruses do not only rely on the host cell for their lipid envelope, but on a lot of
things: energy production, protein synthesis, reproduction
• !!! Bacteria replicate exponentially while viruses don’t!
o First viruses do Brownian movement à (bacteria
has flagella and goes in a specific direction)
o By chance the virus binds to receptor of cells
o Virus is internalized in the cell and degraded in a
controlled manner so the genome can be released.
With replication and translation, new virus particles
can be produced.
o New virus particles are released (gradually or in a burst)
• Are viruses dead/alive à dead
o They cannot produce their own energy (no carbon metabolism)
o They cannot reproduce/ evolve by themselves (obligate intracellular)
o There are no ancestral viral lineages: no single gene has been identified that is
shared by all viruses
o Viruses don’t have a structure derived from a common ancestor, like cells are
all derived from a common ancestor cell because there is ‘membrane
heridity’: during cell division, cells obtain membranes from other cells
2
,2024-2025 Virology
Origin of viruses
• There are 3 scenarios for the origin of viruses:
o Primordial virus world/ virus early hypothesis: the whole world started with
DNA floating around that could replicate
o Escaped genes hypothesis: some genes where present in ancestor cells/
bacteria and just escaped from cells, they were the products of degeneration
of ancestral cells that lost their autonomy (this theory become a thing again
when large viruses were found)
o Reductive virus origin/ regression hypothesis: viruses are remnants of a
degraded cell; it needed another cell to replicate
o Probably a combination of these three!
Di3erent kinds of genome in viruses
• dsDNA à use the DNA-polymerase of cells to replicate à proofreading à less
mutations à less variability à less chance to infect another species because of this
low mutation rate (Herpes is a dsDNA virus, thus Herpes of your cat will probably not
infect you)
• RNA-virus à uses RNA-dependent-RNA-polymerase to replicate à it is not from the
human cells since it does not exist here, so the virus encodes for it à no
proofreading à more mutations à more variability à more chance to cross
species-barrier (SARS-COV-2 is an RNA virus and thus crosses species barriers and
can cause pandemics)
o RNA viruses can be linear/circular or segmented (diaerent RNA-strands next
to each other)
o RNA-viruses don’t need a nucleus to replicate and can stay in cytoplasm
(most of them will still go in nucleus tho)
o + stranded ssRNA will be in cytoplasm (for translation) and – stranded RNA in
cytoplasm or nucleus
o Viruses don’t care about +/- stranded, they mostly are ambisense: you can
read the genome from both sides
• Genome of virus always consists of 2 core modules:
o Encodes for genome replication = non-structural proteins
§ This is used to group diaerent virus families:
• RNA-viruses
o RNA-dependent-RNA-polymerase (RdRp)
o Reverse transcriptase
• DNA-viruses
o Protein primed family B DNAP
o Rolling circle replication endonucleases
o Superfamily 3 helicase
§ The replication machinery might have arisen from the primordial pool
of genetic elements
3
, 2024-2025 Virology
§ 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 diaerent nucleic acid types & non-viral
mobile genetic elements
• RdRp (RNA-dependent RNA polymerase) universally conserved
across all RNA viruses à needed for replicationand 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 diaerent DNA-dependent DNA polymerases
• Retroviruses have reverse transcriptase
o Encodes for structural proteins (capsid)
§ Often: virus makes polyproteïns that are cut by proteases into smaller
proteins
§ Capsids have limited diversity and have the same structural backbone
in every virus = 60% of viruses have an icosahedral structure (looks like
a cristal). Other common capsid structures are rod-
shaped/filamentous or helical
§ Capsid can consist of lipid parts or proteins
§ Every virus had genes that encode for capsid. Some viruses have
genes encoding for receptor-binding proteïns (but sometimes, the
receptor binding proteins van be found on capsid proteïns)
§ The structural proteins may have been acquired from hosts at diaerent
stages of evolution à sequence and structure comparison indicate
that many capsid proteins evolved from ancestral cellular
carbohydrate-binding or nucleic acid-binding capacity and genome
protection
o Viruses can also have other genes than only these 2 core modules:
§ Regulation and timing of replication cycle
§ Modulation of host defense mechanism (this is not immune invasion
because it is not absolute: it will just block the immune response long
enough for virus to replicate)
• Genes that are not encoded in the viral genome
o The genome of viruses does not have telomeres/ centromeres like in
chromosomes
o The viral genome does not have genes encoding protein synthesis machinery
(ribosomes, tRNA)
o The viral genome does not have genes encoding for the membrane synthesis
• Chimeric origin of viruses
o The structural proteins may have been acquired from hosts at diaerent stages
of evolution
o The replication machinery might have arisen from the primordial pool of
genetic elements
4
