P a g e 1 | 107
,1. What are viruses?
✺ Most abundant biological entities on the planet
✺ They are obligate intracellular parasites; while bacteria replicate outside the host, viruses need a living
cell wherein they will replicate
✺ Viruses can also be in a sleeping state, latency, where they are not actively replicating
✺ Viruses are everywhere around and inside of us, even the
human genome consists of viral genetic material
◣ Remnants of retroviruses can be found in LTR
retrotransposons, SINEs, and LINEs
◣ When the genome of a virus is inside of a germline cell, via
infection, it can be passed down generations
✺ On population level viruses are important for maintaining
diversity in the gene pool: if a virus kills 99% of people, then
that 1% survived due to an advantageous mutation and will
create a new group of people carrying that mutation, thus making it common in the new population
✺ There are enormous amounts of viruses/viral particles around us, in one litre sea water are more viruses
than there are people on Earth
◣ Bacteriophages specifically are vital in determining which viruses can survive and which won’t, this is
determined by which viruses are targets for bacteriophages and which aren’t
✺ Aside from the human microbiome consisting of bacteria, there is also a human virome consisting of
viruses
✺ The structure of viruses....
◣ Viruses have a size of between 50-100 nm and are
invisible in the light microscope
⤿ There are exceptions such as the recently
discovered Pandoravirus that has a size of
~1000nm/1 μm
◣ Their shapes can also vary from icosahedral to helical
to snake-like
◣ Their composition too can vary from having an
envelope to only having a capsid and so on
✺ All viruses are obligatory parasites...
◣ They infect all lifeforms: archaea, bacteria,
eukaryotes, plants, and animals
◣ They always have a genome consisting of either DNA or RNA that can be single or double stranded (ss
or ds) and is surrounded by a protein coat named the capsid
⤿ The capsid will thus protect the genetic material as well
as transmit the genetic material by facilitating entry into
the host cell via receptor binding
◣ Some viruses can also have a lipid envelope around the
capsid which was stolen from a host cell
◣ They rely on the host of E-production, protein syntheses
and reproduction
P a g e 2 | 107
,✺ There are certain rules regarding viruses...
◣ All viral genomes are obligate molecular parasites that can only function after they replicate in a cell
◣ All viruses must make mRNA (out of RNA or DNA) that can be translated by the host ribosomes; they
hijack the host protein synthesis machinery and use it to translate their own viral proteins
◣ Viruses are important disease-causing agents, but not all viruses make us sick
⤿ Many viruses can’t actually infect our cells (because they are for example infectious to other species)
and will simply pass through our system
⤿ The ones that do infect us are usually cleaned up by our immune system, when that doesn’t happen,
we get sick
◣ Are viruses alive or dead?
⤿ They don’t have energy production, carbon metabolism
⤿ They cannot replicate or evolve by themselves, only within host cells, without a cell they are
considered inanimate complex organic matter
⤿ There are no ancestral viral lineages: there is no single gene that has been identified that is shared by
all viruses, there are common protein motifs in viral capsids but these likely came about from
convergent evolution or horizontal gene transfer
⤿ They don’t have a structure derived from a common ancestor: cells for example get their cell
membrane from other cells during cell division, here the membrane is hereditary, but this doesn’t
occur in viruses
1.1. Origin of viruses
There are currently three hypotheses for the origin of viruses...
1. ‘Primordial virus world’ or ‘virus early’ hypothesis
✺ There were complex RNA and DNA entities who replicated, and viruses came from them
2. Reactive virus origin or regression hypothesis
✺ Ancestral cells (early proto cells) have degenerated and lost their autonomy and transitioned into
intracellular parasites
✺ This can help explain giant viruses that can encode for almost everything but have no cellular
structures
3. Escaped genes hypothesis
✺ Extracellular vesicles derived from cells have evolved into viruses after acquiring a genome
P a g e 3 | 107
, 1.2. Virus replication – a quick overview
✺ Viruses replicate differently than bacteria and eukaryotic cells
◣ Eukaryotic cells will use mitosis to divide
◣ Bacteria use binary fission to divide
◣ Viruses use the following replication mechanism...
◣ Viruses have a small genome size; they encode for very few proteins including but not limited to the
capsid as well as a polymerase (in RNA viruses this polymerase cannot proofread)
◣ As visible by the graph, we can see that a small genome size equals a high mutation rate (of the
enzyme responsible for copying the genome)
⤿ Because larger genomes usually encode
polymerases with proofreading as well as other DNA
repair proteins, whilst smaller genomes encode for
the bare minimum (such as the capsid in viruses)
⤿ Viruses that cause epidemics and pandemics are
thus usually RNA viruses: their mutation rate is high,
there will be a lot of variation, and some variants will
be able evade the immune system
⤿ Quasispecies: the difference between the virus that enters a host cell and the virus that exits the
host cell due to the high mutation rate, the virus will undergo mutations within the host cell and leave
as a virus with a different genome, so virus species are determined using sequencing rather than
structure
◣ Viruses will thus undergo a lot of mutations
1.3. A typical virus genome
✺ They genome consists of either ss or ds DNA and/or RNA
✺ The genome contains at least two core modules that
consists of genes encoding for proteins required for
genome replication (non-structural proteins) and proteins
involved in virion formation (structural proteins)
✺ There is also a chimeric origin of virus hypothesis that
states that the replication machinery may have risen
from primordial pool of genetic elements whereas the
structural proteins may have been acquired from hosts
at different stages of evolution
P a g e 4 | 107
,1. What are viruses?
✺ Most abundant biological entities on the planet
✺ They are obligate intracellular parasites; while bacteria replicate outside the host, viruses need a living
cell wherein they will replicate
✺ Viruses can also be in a sleeping state, latency, where they are not actively replicating
✺ Viruses are everywhere around and inside of us, even the
human genome consists of viral genetic material
◣ Remnants of retroviruses can be found in LTR
retrotransposons, SINEs, and LINEs
◣ When the genome of a virus is inside of a germline cell, via
infection, it can be passed down generations
✺ On population level viruses are important for maintaining
diversity in the gene pool: if a virus kills 99% of people, then
that 1% survived due to an advantageous mutation and will
create a new group of people carrying that mutation, thus making it common in the new population
✺ There are enormous amounts of viruses/viral particles around us, in one litre sea water are more viruses
than there are people on Earth
◣ Bacteriophages specifically are vital in determining which viruses can survive and which won’t, this is
determined by which viruses are targets for bacteriophages and which aren’t
✺ Aside from the human microbiome consisting of bacteria, there is also a human virome consisting of
viruses
✺ The structure of viruses....
◣ Viruses have a size of between 50-100 nm and are
invisible in the light microscope
⤿ There are exceptions such as the recently
discovered Pandoravirus that has a size of
~1000nm/1 μm
◣ Their shapes can also vary from icosahedral to helical
to snake-like
◣ Their composition too can vary from having an
envelope to only having a capsid and so on
✺ All viruses are obligatory parasites...
◣ They infect all lifeforms: archaea, bacteria,
eukaryotes, plants, and animals
◣ They always have a genome consisting of either DNA or RNA that can be single or double stranded (ss
or ds) and is surrounded by a protein coat named the capsid
⤿ The capsid will thus protect the genetic material as well
as transmit the genetic material by facilitating entry into
the host cell via receptor binding
◣ Some viruses can also have a lipid envelope around the
capsid which was stolen from a host cell
◣ They rely on the host of E-production, protein syntheses
and reproduction
P a g e 2 | 107
,✺ There are certain rules regarding viruses...
◣ All viral genomes are obligate molecular parasites that can only function after they replicate in a cell
◣ All viruses must make mRNA (out of RNA or DNA) that can be translated by the host ribosomes; they
hijack the host protein synthesis machinery and use it to translate their own viral proteins
◣ Viruses are important disease-causing agents, but not all viruses make us sick
⤿ Many viruses can’t actually infect our cells (because they are for example infectious to other species)
and will simply pass through our system
⤿ The ones that do infect us are usually cleaned up by our immune system, when that doesn’t happen,
we get sick
◣ Are viruses alive or dead?
⤿ They don’t have energy production, carbon metabolism
⤿ They cannot replicate or evolve by themselves, only within host cells, without a cell they are
considered inanimate complex organic matter
⤿ There are no ancestral viral lineages: there is no single gene that has been identified that is shared by
all viruses, there are common protein motifs in viral capsids but these likely came about from
convergent evolution or horizontal gene transfer
⤿ They don’t have a structure derived from a common ancestor: cells for example get their cell
membrane from other cells during cell division, here the membrane is hereditary, but this doesn’t
occur in viruses
1.1. Origin of viruses
There are currently three hypotheses for the origin of viruses...
1. ‘Primordial virus world’ or ‘virus early’ hypothesis
✺ There were complex RNA and DNA entities who replicated, and viruses came from them
2. Reactive virus origin or regression hypothesis
✺ Ancestral cells (early proto cells) have degenerated and lost their autonomy and transitioned into
intracellular parasites
✺ This can help explain giant viruses that can encode for almost everything but have no cellular
structures
3. Escaped genes hypothesis
✺ Extracellular vesicles derived from cells have evolved into viruses after acquiring a genome
P a g e 3 | 107
, 1.2. Virus replication – a quick overview
✺ Viruses replicate differently than bacteria and eukaryotic cells
◣ Eukaryotic cells will use mitosis to divide
◣ Bacteria use binary fission to divide
◣ Viruses use the following replication mechanism...
◣ Viruses have a small genome size; they encode for very few proteins including but not limited to the
capsid as well as a polymerase (in RNA viruses this polymerase cannot proofread)
◣ As visible by the graph, we can see that a small genome size equals a high mutation rate (of the
enzyme responsible for copying the genome)
⤿ Because larger genomes usually encode
polymerases with proofreading as well as other DNA
repair proteins, whilst smaller genomes encode for
the bare minimum (such as the capsid in viruses)
⤿ Viruses that cause epidemics and pandemics are
thus usually RNA viruses: their mutation rate is high,
there will be a lot of variation, and some variants will
be able evade the immune system
⤿ Quasispecies: the difference between the virus that enters a host cell and the virus that exits the
host cell due to the high mutation rate, the virus will undergo mutations within the host cell and leave
as a virus with a different genome, so virus species are determined using sequencing rather than
structure
◣ Viruses will thus undergo a lot of mutations
1.3. A typical virus genome
✺ They genome consists of either ss or ds DNA and/or RNA
✺ The genome contains at least two core modules that
consists of genes encoding for proteins required for
genome replication (non-structural proteins) and proteins
involved in virion formation (structural proteins)
✺ There is also a chimeric origin of virus hypothesis that
states that the replication machinery may have risen
from primordial pool of genetic elements whereas the
structural proteins may have been acquired from hosts
at different stages of evolution
P a g e 4 | 107
