GENERAL INTRODUCTION
WHY DO WE STUDY VIRUSES?
Viruses are everywhere;
-> they infiltrate every aspect of our natural world, seething in seawater, drifting through the atmosphere, and
lurking in miniscule motes of soil.
- In the water -> whales are commonly infected with a member of the virus family Caliciviridae that can
also infect humans.
o Infected whales excrete more than 1013 calicivirus particles daily -> remain viable more than
14 days in 15°C seawater.
!! Viruses can now be classified based on just their genome, instead of researchers having to culture the virus
and its host -> scientists found and logged viruses in huge numbers in recent years.
Viruses can cause human disease
- BUT the vast majority of viruses that infect us have little or no impact on our health or well-being ->
most viruses just pass through us.
o We ingest many non-animal viruses regularly with foods!
o This relative safety depends on our elaborate immune defense systems, which have evolved
to fight microbial infection.
- Despite such defenses, some of the most devastating human diseases have been or still are caused by
viruses; these diseases include smallpox, yellow fever, poliomyelitis, influenza, measles, and AIDS
o Can lead to life-threatening diseases that impact virtually all organs, including the lungs, liver,
central nervous system, and intestines.
o Responsible for approximately 20% of the human cancer burden, and viral infections of the
respiratory and gastrointestinal tracts kill millions of children each year.
Viruses infect all living things;
- Also infect pets, food animals, plants, insects, and wildlife throughout the world.
- They infect microbes such as algae, fungi, and bacteria, and some even interfere with the reproduction
of other viruses.
-> can have enormous economic and societal impact.
Viruses can be beneficial;
- In marine ecology, virus particles are the most abundant biological entities.
o 94% of all nucleic acid-containing particles in the oceans.
o 15x more abundant than the Bacteria and Archaea.
o Viral infections in the ocean kill 20-40% of marine microbes daily -> release essential
nutrients that supply phytoplankton (food), as well as carbon dioxide and other gases that
affect the climate of the earth.
- Pathogens can also influence one another -> infection by one virus can have an ameliorating effect on
the pathogenesis of a second virus or even bacteria.
1
, Example:
o Human immunodeficiency virus-infected AIDS patients show a substantial decrease in their
disease progression if they are persistently infected with hepatitis G virus.
o Mice latently infected with some murine herpesviruses are resistant to infection with the
bacterial pathogens Listeria monocytogenes and Yersinia pestis.
Viruses can cross species boundaries;
!! Viruses generally have a limited host range, yet they can and do spread across species barriers !!
-> As the world’s human population continues to expand and impinge on the wilderness, cross-species
(zoonotic) infections of humans are occurring with increasing frequency.
- In addition to the AIDS pandemic, the highly fatal Ebola hemorrhagic fever and the SARS and SARS-
CoV-2 are recent examples of viral diseases to emerge from zoonotic infections.
- Current pandemic of influenza virus H5N1 in avian -> frightening possibility of transmission to humans
of a highly pathogenic strain.
We are viruses – viruses are us – viruses drive human evolution;
!! Every cell in our body contains viral DNA !!
- Human endogenous retroviruses, and elements thereof, make up about 5 to 8% of our DNA.
o Most are inactive, fossil remnants from infections of germ cells that have occurred over
millions of years during our evolution.
o Some of them are suspected to be associated with specific diseases, but the protein products
of other endogenous retroviruses are essential!
Transposable elements (TE) -> TE discovery dates back to the 1940s, yet it took
about half a century before we understand the importance: a crucial stage was
reached with the completion of the first human genome sequence
→ nearly half of our genome is derived from different types of TE.
Retrotransposons (Class I transposable elements or transposons via RNA
intermediates) - long terminal repeats (LTRs) transposons
= type of genetic component that copy and paste themselves into different
genomic locations (transposon) by converting RNA back into DNA through the
process reverse transcription using an RNA transposition intermediate.
DNA transposons <-> “jumping genes” (’cut and paste’; no RNA intermediate)
= discrete pieces of DNA that can move from site to site within (and sometimes between) genomes.
SINEs and LINEs
= short and long interspersed retrotransposable elements, that invade new genomic sites using RNA
intermediates.
o ‘copy and paste’
o Non-LTR transposons
o Are found in almost all eukaryotes (although not in S. cerevisiae) and together account for at
least 34% of the human genome.
2
,Viruses have been part of all of human history -> they were present long before Homo sapiens evolved, and the
majority of human infections were likely acquired from other animals (zoonoses).
- Epidemics most likely have shaped which species and populations have been successful to reproduce
and expand.
- As viruses continue to be discovered, our understanding of how human health and well-being are
affected by these agents remains incomplete.
Example: protein products of endogenous retroviruses are essential for who we are as a species
- A gene of viral origin encodes for a protein that plays a key role in long-term memory formation by
moving information between cells in the nervous system.
- Evolution of the mammalian placenta and the timing of gene expression in human pregnancy depends
on a bit of genetic code that was co-opted from ancient retroviruses that infected our ancestors >130
million years ago.
The disappearance of viruses would impact the evolutionary potential for all life on the planet – including
Homo sapiens;
- Because viruses are constantly replicating and mutating, viruses also hold a massive repository of
genetic innovation that other organisms can incorporate
- Viruses replicate by inserting themselves into host cells and hijacking their replication tools. → If this
happens in a germline cell, the viral code can be passed on to the next generation and become
permanently integrated
!! The insertion of new DNA into genomes is a major mode of evolution !!
Viruses are unique tools to study cell biology;
-> because viruses are dependent on their hosts for propagation, studies that focus on viral reprogramming of
cellular mechanisms have provided unique insights into cellular biology and functioning of host defenses.
- Groundbreaking studies of viruses that infect bacteria, the bacteriophages, laid the foundations of
modern molecular biology!
WHAT IS A VIRUS?
Virus size;
Herpesviruses are large, while polioviruses are small.
LM isn’t sufficient for studying viruses, we usually use EM. To
do structure analysis you need X-ray and NMR.
3
, All viruses have 2 things in common;
1. Each encases its genome in a protein-based shell.
2. Each relies on its host (a person, spider or plant) to reproduce itself.
!! but beyond that general pattern lie endless variations !!
A virus is an organism with 2 phases;
- Virion (infectious particle) = the complete, infective form of a virus outside a host cell, with a core of
RNA and a capsid.
- Infected cell
→ generally considered non-living entities, these pathogens can only replicate with the help of a host, and they
are capable of hijacking organisms from every branch of the tree of life—including a multitude of human cells.
An infectious, obligate intracellular parasite comprising genetic material (DNA or RNA), often surrounded by
a protein coat, sometimes a membrane
The properties of viruses:
- A virus is an infectious, obligate intracellular parasite;
- The viral genome comprises DNA or RNA;
- The viral genome directs the synthesis of viral components by cellular systems within an appropriate
host cell;
- Infectious progeny virus particles, called virions, are formed by de novo self-assembly from newly
synthesized components;
- A progeny virion assembled during the infectious cycle is the vehicle for transmission of the viral
genome to the next host cell or organism, where its disassembly initiates the next infectious cycle.
While viruses lack the complex energy-generating and biosynthetic systems necessary for independent
existence, they are not the simplest biologically active agents:
- Viroids: infectious agents of a variety of economically important plants, comprise a single small
molecule of noncoding RNA. They have no protein coating.
o Most cause diseases, whose respective economic importance to humans varies widely.
- Prions: misfolded proteins with the ability to transmit their misfolded shape onto normal variants
of the same protein.
o They characterize several fatal and transmissible neurodegenerative diseases in humans
and many other animals
DISCOVERY OF VIRUSES
Filterable viruses;
- 1892 – Ivanovsky
- 1989 – Beijernick -> contagium vivum fluidum
o Virus = poison (in liquid form)
-> agent of tobacco mosaic disease passed through filters that retain bacteria.
1939 – viruses are not liquids!
4
WHY DO WE STUDY VIRUSES?
Viruses are everywhere;
-> they infiltrate every aspect of our natural world, seething in seawater, drifting through the atmosphere, and
lurking in miniscule motes of soil.
- In the water -> whales are commonly infected with a member of the virus family Caliciviridae that can
also infect humans.
o Infected whales excrete more than 1013 calicivirus particles daily -> remain viable more than
14 days in 15°C seawater.
!! Viruses can now be classified based on just their genome, instead of researchers having to culture the virus
and its host -> scientists found and logged viruses in huge numbers in recent years.
Viruses can cause human disease
- BUT the vast majority of viruses that infect us have little or no impact on our health or well-being ->
most viruses just pass through us.
o We ingest many non-animal viruses regularly with foods!
o This relative safety depends on our elaborate immune defense systems, which have evolved
to fight microbial infection.
- Despite such defenses, some of the most devastating human diseases have been or still are caused by
viruses; these diseases include smallpox, yellow fever, poliomyelitis, influenza, measles, and AIDS
o Can lead to life-threatening diseases that impact virtually all organs, including the lungs, liver,
central nervous system, and intestines.
o Responsible for approximately 20% of the human cancer burden, and viral infections of the
respiratory and gastrointestinal tracts kill millions of children each year.
Viruses infect all living things;
- Also infect pets, food animals, plants, insects, and wildlife throughout the world.
- They infect microbes such as algae, fungi, and bacteria, and some even interfere with the reproduction
of other viruses.
-> can have enormous economic and societal impact.
Viruses can be beneficial;
- In marine ecology, virus particles are the most abundant biological entities.
o 94% of all nucleic acid-containing particles in the oceans.
o 15x more abundant than the Bacteria and Archaea.
o Viral infections in the ocean kill 20-40% of marine microbes daily -> release essential
nutrients that supply phytoplankton (food), as well as carbon dioxide and other gases that
affect the climate of the earth.
- Pathogens can also influence one another -> infection by one virus can have an ameliorating effect on
the pathogenesis of a second virus or even bacteria.
1
, Example:
o Human immunodeficiency virus-infected AIDS patients show a substantial decrease in their
disease progression if they are persistently infected with hepatitis G virus.
o Mice latently infected with some murine herpesviruses are resistant to infection with the
bacterial pathogens Listeria monocytogenes and Yersinia pestis.
Viruses can cross species boundaries;
!! Viruses generally have a limited host range, yet they can and do spread across species barriers !!
-> As the world’s human population continues to expand and impinge on the wilderness, cross-species
(zoonotic) infections of humans are occurring with increasing frequency.
- In addition to the AIDS pandemic, the highly fatal Ebola hemorrhagic fever and the SARS and SARS-
CoV-2 are recent examples of viral diseases to emerge from zoonotic infections.
- Current pandemic of influenza virus H5N1 in avian -> frightening possibility of transmission to humans
of a highly pathogenic strain.
We are viruses – viruses are us – viruses drive human evolution;
!! Every cell in our body contains viral DNA !!
- Human endogenous retroviruses, and elements thereof, make up about 5 to 8% of our DNA.
o Most are inactive, fossil remnants from infections of germ cells that have occurred over
millions of years during our evolution.
o Some of them are suspected to be associated with specific diseases, but the protein products
of other endogenous retroviruses are essential!
Transposable elements (TE) -> TE discovery dates back to the 1940s, yet it took
about half a century before we understand the importance: a crucial stage was
reached with the completion of the first human genome sequence
→ nearly half of our genome is derived from different types of TE.
Retrotransposons (Class I transposable elements or transposons via RNA
intermediates) - long terminal repeats (LTRs) transposons
= type of genetic component that copy and paste themselves into different
genomic locations (transposon) by converting RNA back into DNA through the
process reverse transcription using an RNA transposition intermediate.
DNA transposons <-> “jumping genes” (’cut and paste’; no RNA intermediate)
= discrete pieces of DNA that can move from site to site within (and sometimes between) genomes.
SINEs and LINEs
= short and long interspersed retrotransposable elements, that invade new genomic sites using RNA
intermediates.
o ‘copy and paste’
o Non-LTR transposons
o Are found in almost all eukaryotes (although not in S. cerevisiae) and together account for at
least 34% of the human genome.
2
,Viruses have been part of all of human history -> they were present long before Homo sapiens evolved, and the
majority of human infections were likely acquired from other animals (zoonoses).
- Epidemics most likely have shaped which species and populations have been successful to reproduce
and expand.
- As viruses continue to be discovered, our understanding of how human health and well-being are
affected by these agents remains incomplete.
Example: protein products of endogenous retroviruses are essential for who we are as a species
- A gene of viral origin encodes for a protein that plays a key role in long-term memory formation by
moving information between cells in the nervous system.
- Evolution of the mammalian placenta and the timing of gene expression in human pregnancy depends
on a bit of genetic code that was co-opted from ancient retroviruses that infected our ancestors >130
million years ago.
The disappearance of viruses would impact the evolutionary potential for all life on the planet – including
Homo sapiens;
- Because viruses are constantly replicating and mutating, viruses also hold a massive repository of
genetic innovation that other organisms can incorporate
- Viruses replicate by inserting themselves into host cells and hijacking their replication tools. → If this
happens in a germline cell, the viral code can be passed on to the next generation and become
permanently integrated
!! The insertion of new DNA into genomes is a major mode of evolution !!
Viruses are unique tools to study cell biology;
-> because viruses are dependent on their hosts for propagation, studies that focus on viral reprogramming of
cellular mechanisms have provided unique insights into cellular biology and functioning of host defenses.
- Groundbreaking studies of viruses that infect bacteria, the bacteriophages, laid the foundations of
modern molecular biology!
WHAT IS A VIRUS?
Virus size;
Herpesviruses are large, while polioviruses are small.
LM isn’t sufficient for studying viruses, we usually use EM. To
do structure analysis you need X-ray and NMR.
3
, All viruses have 2 things in common;
1. Each encases its genome in a protein-based shell.
2. Each relies on its host (a person, spider or plant) to reproduce itself.
!! but beyond that general pattern lie endless variations !!
A virus is an organism with 2 phases;
- Virion (infectious particle) = the complete, infective form of a virus outside a host cell, with a core of
RNA and a capsid.
- Infected cell
→ generally considered non-living entities, these pathogens can only replicate with the help of a host, and they
are capable of hijacking organisms from every branch of the tree of life—including a multitude of human cells.
An infectious, obligate intracellular parasite comprising genetic material (DNA or RNA), often surrounded by
a protein coat, sometimes a membrane
The properties of viruses:
- A virus is an infectious, obligate intracellular parasite;
- The viral genome comprises DNA or RNA;
- The viral genome directs the synthesis of viral components by cellular systems within an appropriate
host cell;
- Infectious progeny virus particles, called virions, are formed by de novo self-assembly from newly
synthesized components;
- A progeny virion assembled during the infectious cycle is the vehicle for transmission of the viral
genome to the next host cell or organism, where its disassembly initiates the next infectious cycle.
While viruses lack the complex energy-generating and biosynthetic systems necessary for independent
existence, they are not the simplest biologically active agents:
- Viroids: infectious agents of a variety of economically important plants, comprise a single small
molecule of noncoding RNA. They have no protein coating.
o Most cause diseases, whose respective economic importance to humans varies widely.
- Prions: misfolded proteins with the ability to transmit their misfolded shape onto normal variants
of the same protein.
o They characterize several fatal and transmissible neurodegenerative diseases in humans
and many other animals
DISCOVERY OF VIRUSES
Filterable viruses;
- 1892 – Ivanovsky
- 1989 – Beijernick -> contagium vivum fluidum
o Virus = poison (in liquid form)
-> agent of tobacco mosaic disease passed through filters that retain bacteria.
1939 – viruses are not liquids!
4
