1
SAMENVATTING VIROLOGIE
INTRODUCTION
WHAT IS A VIRUS?
• Obligate intracellular parasites
• Virion = genome packed into lipid particles (‘like a seeds that comes alive when entering the cell’ =
obligate intracellular)
• 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 wille 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)
• There is variability in the genome of viruses
o They don’t have a DNA-repair mechanism, thus most of the replication have a lot of mutation
resulting in a virus that cannot infect = junk-viruses.
o The variability in virus genome is important to be able to evade immune system host (=
survival of the fittest) !!!
• Viruses differ in structure, but minimal components: (very small viruses don’t fit a big genome: only
codes for capsid protein, so they rely on the host genome for the rest) (all viruses must ‘make’ mRNA
to make proteïns)
o Genome: can be dsDNA/ ssDNA/ dsRNA/ ssRNA à + stranded RNA/ - stranded RNA
o Capsid protein = capsid around genome of virus
o Capsid + genome = nucleocapsid = virion
o All viruses have capsid proteins, but not all of these form a very stable crystal like capsid
structure!!!
o Virion + things that come to expression when a virus infects a cell = virus
• 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 don’t only rely on host cell for lipid envelope but on a lot of things: energy production,
protein synthesis, reproduction
, 2
• !!! Bacteria replicate exponentially while viruses don’t!
o First viruses do Brownian movement. (bacteria has flagella
and goes in a specific direction)
o By chance the virus binds to receptor of cells
o Virus in 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: they cannot produce their own
energy (no carbon metabolism) & they cannot reproduce/ evolve by
themselves (obligate intracellular) & there are no ancestral viral lineages: no single gene has been
identified that is shared by all viruses & 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.)
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.
o Reductive virus origin/ regression hypothesis: viruses are remnants of a degraded cell: it
needed another cell to replicate.
DIFFERENT 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 (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 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 thus crosses species
barriers and can cause pandemics.)
o RNA viruses can have a linear/ circular or segmented: different 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 of
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 different virus families:
• RNA-viruses
o RNA-dependent-RNA-polymerase (RdRp)
, 3
o Reverse transcriptase
• DNA-viruses
o Protein primed family B DNAP
o Rolling circle replication endonucleases
o Superfamily 3 helicase
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
= icosahedral structure (looks like a cristal). Thus the structural genes are most likely
derived from cells.
§ 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)
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
KOCH’S POSTULATES (VOOR DE ZOVEELSTE KEER DEZE STUDIE)
• Koch’s postulates used to affirm the causes of infectious diseases (mogelijk examen!)
o Causative agent is present is all diseased, but absent in all healthy species
o Causative agent must be isolated from organism and grown in pure culture
o Causative agent must cause the same disease when inoculated in healthy organism
o Causative agent must be re-isolated from inoculated diseased organism
• But not all diseases could be explained this way, some ‘causative agents’ would pass through the
filters and still cause disease. It was first thought that it was the fluid that caused the disease =
poison à latin for poison = virus
• 21st century revised postulates of Koch: 3 critical changes
o We don’t look if pathogen can grow or not, we look at nucleic acid
o We don’t look at if something is absent/ present, but we look at relative values
o We don’t look at organism as a whole, but at the cells/ tissue that is diseased
VIRUS CLASSIFICATION
• ICTV-classification = international committee of taxonomy of viruses = Needed to talk about same
virus worldwide, however, the classification changes a lot.
• ICTV-classification uses following taxonomic units:
o Order (not all viruses are assigned an order) (orders end with -virales)
o Family (ends with -viridae)
, 4
o Genus (ends with -virus)
o Species
• There also is a functional classification system = Baltimore classification system:
• 7 classes of viruses depending on how they make mRNA and replicate their genome
o Class I: dsDNA
§ Need DNA-polymerase (DdDp) from cell to replicate (has proofreading)
§ Needs RNA-polymerase from cell to make mRNA (+ stranded)
§ Example: adenovirus & Herpes virus (has special form of assembly)
o Class II: ssDNA
§ Needs DNA-dependent-DNA-polymerase (DdDp) to form dsDNA from ssRNA. DdDp
is only present in rapidly dividing cells: rapidly dividing cells express DdDp when they
divide.
§ From the dsDNA the RNA-polymerase from cell kan make mRNA (+ stranded)
§ Example: parvoviruses
o Class III: dsRNA
§ Has both + stranded and – stranded RNA (only + stranded RNA can be used for the
translation to proteïns)
§ There are not much dsRNA viruses: probably because our immunesystem reacts
very violently to dsRNA. Thus, these viruses will not release their genome in the cell
but will protect their dsRNA with their capsid. There are small pores in the capsid
that will allow the ssRNA to escapte to cytoplasm for translation.
§ To form a new virion, the capsid is first partially formed befored the dsRNA is
inserted.
§ These are seen as the ancestors that preceed other RNA-viruses: In most
vertebrates these dsRNA viruses are extinct.
§ Example: Rotavirus
o Class IV: ssRNA + stranded
§ The + stranded mRNA can be used directly by the cellular ribosomes to produce
proteins: It codes for polymerase complex (for replication) and for double membrane
vesicles (DMV) (discussed later) that can protect the replicating RNA and that will
assemble the polymerase complex.
§ The + stranded mRNA must be replicated to form a new genome: to do this is must
first be converted to – stranded RNA before + stranded RNA can be made again. This
is done using RdRp
§ Example: flaviviruses & alfaviruses (alfaviruses is special, see later)
o Class V: ssRNA – stranded
§ This cannot be used by the ribosomes for translation: it must be replicated to +
stranded RNA using RdRp.
SAMENVATTING VIROLOGIE
INTRODUCTION
WHAT IS A VIRUS?
• Obligate intracellular parasites
• Virion = genome packed into lipid particles (‘like a seeds that comes alive when entering the cell’ =
obligate intracellular)
• 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 wille 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)
• There is variability in the genome of viruses
o They don’t have a DNA-repair mechanism, thus most of the replication have a lot of mutation
resulting in a virus that cannot infect = junk-viruses.
o The variability in virus genome is important to be able to evade immune system host (=
survival of the fittest) !!!
• Viruses differ in structure, but minimal components: (very small viruses don’t fit a big genome: only
codes for capsid protein, so they rely on the host genome for the rest) (all viruses must ‘make’ mRNA
to make proteïns)
o Genome: can be dsDNA/ ssDNA/ dsRNA/ ssRNA à + stranded RNA/ - stranded RNA
o Capsid protein = capsid around genome of virus
o Capsid + genome = nucleocapsid = virion
o All viruses have capsid proteins, but not all of these form a very stable crystal like capsid
structure!!!
o Virion + things that come to expression when a virus infects a cell = virus
• 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 don’t only rely on host cell for lipid envelope but on a lot of things: energy production,
protein synthesis, reproduction
, 2
• !!! Bacteria replicate exponentially while viruses don’t!
o First viruses do Brownian movement. (bacteria has flagella
and goes in a specific direction)
o By chance the virus binds to receptor of cells
o Virus in 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: they cannot produce their own
energy (no carbon metabolism) & they cannot reproduce/ evolve by
themselves (obligate intracellular) & there are no ancestral viral lineages: no single gene has been
identified that is shared by all viruses & 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.)
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.
o Reductive virus origin/ regression hypothesis: viruses are remnants of a degraded cell: it
needed another cell to replicate.
DIFFERENT 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 (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 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 thus crosses species
barriers and can cause pandemics.)
o RNA viruses can have a linear/ circular or segmented: different 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 of
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 different virus families:
• RNA-viruses
o RNA-dependent-RNA-polymerase (RdRp)
, 3
o Reverse transcriptase
• DNA-viruses
o Protein primed family B DNAP
o Rolling circle replication endonucleases
o Superfamily 3 helicase
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
= icosahedral structure (looks like a cristal). Thus the structural genes are most likely
derived from cells.
§ 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)
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
KOCH’S POSTULATES (VOOR DE ZOVEELSTE KEER DEZE STUDIE)
• Koch’s postulates used to affirm the causes of infectious diseases (mogelijk examen!)
o Causative agent is present is all diseased, but absent in all healthy species
o Causative agent must be isolated from organism and grown in pure culture
o Causative agent must cause the same disease when inoculated in healthy organism
o Causative agent must be re-isolated from inoculated diseased organism
• But not all diseases could be explained this way, some ‘causative agents’ would pass through the
filters and still cause disease. It was first thought that it was the fluid that caused the disease =
poison à latin for poison = virus
• 21st century revised postulates of Koch: 3 critical changes
o We don’t look if pathogen can grow or not, we look at nucleic acid
o We don’t look at if something is absent/ present, but we look at relative values
o We don’t look at organism as a whole, but at the cells/ tissue that is diseased
VIRUS CLASSIFICATION
• ICTV-classification = international committee of taxonomy of viruses = Needed to talk about same
virus worldwide, however, the classification changes a lot.
• ICTV-classification uses following taxonomic units:
o Order (not all viruses are assigned an order) (orders end with -virales)
o Family (ends with -viridae)
, 4
o Genus (ends with -virus)
o Species
• There also is a functional classification system = Baltimore classification system:
• 7 classes of viruses depending on how they make mRNA and replicate their genome
o Class I: dsDNA
§ Need DNA-polymerase (DdDp) from cell to replicate (has proofreading)
§ Needs RNA-polymerase from cell to make mRNA (+ stranded)
§ Example: adenovirus & Herpes virus (has special form of assembly)
o Class II: ssDNA
§ Needs DNA-dependent-DNA-polymerase (DdDp) to form dsDNA from ssRNA. DdDp
is only present in rapidly dividing cells: rapidly dividing cells express DdDp when they
divide.
§ From the dsDNA the RNA-polymerase from cell kan make mRNA (+ stranded)
§ Example: parvoviruses
o Class III: dsRNA
§ Has both + stranded and – stranded RNA (only + stranded RNA can be used for the
translation to proteïns)
§ There are not much dsRNA viruses: probably because our immunesystem reacts
very violently to dsRNA. Thus, these viruses will not release their genome in the cell
but will protect their dsRNA with their capsid. There are small pores in the capsid
that will allow the ssRNA to escapte to cytoplasm for translation.
§ To form a new virion, the capsid is first partially formed befored the dsRNA is
inserted.
§ These are seen as the ancestors that preceed other RNA-viruses: In most
vertebrates these dsRNA viruses are extinct.
§ Example: Rotavirus
o Class IV: ssRNA + stranded
§ The + stranded mRNA can be used directly by the cellular ribosomes to produce
proteins: It codes for polymerase complex (for replication) and for double membrane
vesicles (DMV) (discussed later) that can protect the replicating RNA and that will
assemble the polymerase complex.
§ The + stranded mRNA must be replicated to form a new genome: to do this is must
first be converted to – stranded RNA before + stranded RNA can be made again. This
is done using RdRp
§ Example: flaviviruses & alfaviruses (alfaviruses is special, see later)
o Class V: ssRNA – stranded
§ This cannot be used by the ribosomes for translation: it must be replicated to +
stranded RNA using RdRp.
