Virology
1. An introduction to virology
What are viruses? Where do they originate?
- Most abundant biological entities on the planet
- Major roles in global ecology and 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 and eat billions of virus particles
- Human DNA consists partly of ancestral viral genetic material (a lot of transposable elements has
ancestral viral material).
- A lot of viruses have a zoological background and comes over to humans.
Staggering number of viruses on Earth:
- > 1016 HIV particles on Earth
- More viruses in a liter of sea water than people on earth (most abundant organisms on the
planet). But in biomass: a very small part. Viruses are minimal structures.
- > 1030 bacteriophages (living on bacteria) in our seas
- Viruses are everywhere: in soils, on animals, in hot water springs, …
The Human Microbiome
- Bacteria are living on our skins and in major organ systems. Bacteria also covered by viruses (=
virome); many viruses live from these bacteria.
- The human virome and the global virome: each anatomical system mapped out which viruses
are where and which ones cause diseases. Only a minimal fractur of viruses infect humans and
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. A lot of
transposable items had relics of ancestral viruses. Functions at this
moment is unknown.
Viruses are small
- Bacteria: with LM
- Virus: at the edge of what we can see with the LM
- EM: here you can see the virus better
- Effect of virus on cell is visible. Also different microscopical
approaches can be used (angstrom level).
- Mimivirus (400 nm) and pandoravirus (1000nm): unusually large
viruses: these giant viruses are recently discovered. They approach
the size of bacteria. These are viruses that live on amoeba; first thought that they were bacteria, but not
the typical build/organistaion of bacteria. They have double stranded DNA.
1
,Viruses are diverse in structure
- Many particles are spherical
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 and
reproduction
- 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
- 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
Viruses have high genome evolution rates
- Viruses evolve rapidly. Think of corona: when it came to Europe, it was a mutant form. 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. An exact copy of genetic material is required.
- RNA viruses: smaller genome.
- All viruses typically have higher mutation rates than bacteria.
- Coronavirus is a RNA virus with largest genome we know.
- RNA molecules can tolerate a max. of 30 kb genome.
Are viruses dead, alive or anything in between?
- Comparison of cellular and viral traits:
- Cells that we see today have old membranes, carried over by mother cells during cell division. Viruses
don’t have this common structure that is inherited
- Most important reasons to exclude viruses from the tree of life
o Viruses are not alive:
Viruses lack any form of energy, carbon metabolism, and cannot replicate or evolve by
themselves. They are reproduced only within cells, and they also evolve within cells. Without
cells, viruses are “inanimate complex organic matter”. Viruses are ‘death material’.
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.
2
, 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,
and provides evidence that cells are derived from a common ancestor. Viruses have no such
inherited structure.
Origin of viruses?
- Three traditional scenario’s:
o ‘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.
o ‘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.
o ‘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.
- 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).
3
, - The structural proteins may have been acquired from hosts at different stages of evolution (already
developed).
Five hallmark viral replication genes
- Unlike mammalians or humans; viruses doesn’t have specific genes
that classifies them as viruses.
- No close homologues in cellular life, but shared by diverse viruses.
- Links viruses with different nucleic acid types and non-viral mobile
genetic elements.
- RdRp (RNA-dependent RNA polymerase) universally conserved
across all RNA viruses; needed for replication and translation.
- DNA viruses: use other things for replication.
Evolution of viral and cellular replication modules from the ancestral RNA Recognition Motif (RRM)
- RRM is one of the most common RNA-binding domains and occurs in all forms of cellular life
- Structurally related domains are widespread in many viruses and mobile genetic elements
Cellular ancestry of capsids
- Viral capsids have limited diversity
- About 60% of viruses have an icosahedral structure
- Other common capsid structures are rod-shaped/filamentous, or helical
- Sequence & structure comparison indicates that many capsid proteins evolved from ancestral cellular
carbohydrate-binding or nucleic acid-binding proteins, conferring receptor-binding capacity and
genome protection, respectively.
Virus replication
- Not by binary fission like bacterial cells
- Viruses replicate by entering a cell → dissolves in cells
(eclipse phase) → releases genetic material (burst
phase). During eclipse phase you don’t see viruses in
endoplasm.
- All viral material that is produced by own cells → particle.
That can lead to cell that produces hundreds or
thousands of viruses.
A brief history of virology
- 3000 BC: Rinderpest hit the ancient world, considered one of the Egyptian plagues
- 2000 BC: written reports on Rabies in the Mesopotamian Codex of Eshnunna
- 1400 BC: pictogram of a victim of Poliomyelitis in the funerary stele of Egyptian priest Ruma
- 500 BC: first records of possible flu pandemics
- 1200-1800: Smallpox decimates native population of the Americas after arrival of the colonisers
- ‘Variolation’ in 11th century China: Variolation came to EU when he started vaccination avant-la-lettre.
There was no knowledge about origin of sickness (virus) or about the agent (i.e. variola virus) → survivors
of small pox victims seemed to be resistant/protected to pox and subsequent disease. He used bovine
pox to engraft ‘vaccinate’ someone.
- Basis for vaccination by Dr. Edward Jenner in 1796: milk maids came back with cow pox (soars on hands)
and didn’t get sick of human variant. There must be a connection. Jenner inoculated smallpox in the son
of the gardener: smallpox of cow in the arm of the son. This son never got sick of smallpox, but died at
the age of 20 due to TBC.
4
