VIROLOGY: SAMENVATTING
1. WHAT ARE VIRUSES?
• most obundant biological entities on earth
• have a high genome evolution rate
• MAJOR role in global ecology + evolution of biosphere
• Obligate intracellular parasites
o -> package their genomes into tiny protein/lipid particles
• biomass wise only small part bc very tiny + min. structures
• All harbour distinctive repertoires of viruses -> eat + breath billions of virus particles
• Human DNA > partly remnants of ancestral viral genetic material
• Diverse in structure
o many are spherical + little/small
o also unusual large viruses (normally they are pretty small)
§ PANDOVIRUS & MIMIVIRUS
§ approach sizes of bacteria
§ viruses also found living on amoeba
1.1. OLBLIGATORY INTRACELLULAR PARASITES
• infect each life form: plants, animals, eukaryotes, bacteria
• DNA or RNA, ss or ds, protein coat, +/- lipid envelope
o protein core surrounded by lipid membrane from ‘host cell’
o naked virus: genetic material w/ protein coat
o enveloped: protein coat + lipid membrane
• Rely on host cell for energy production, protein synthesis and reproduction
o virus code only for a few proteins -> viral proteins gave to interact w/ other proteins
• All viral genomes = obligate molecular parasites -> can only function after replication in cell
• All viruses must make mRNA that can be translated by host ribosomes -> all parasites of the host
protein synthesis machinery
• important disease-causing agents, but not all viruses make us sick
o Many just passengers through body (food intake, breathing)
§ immune system learned to deal with (some) viruses
1.2. RE VIRUSES DEAD, ALIVE OF ANYTHING IN BETWEEN?
There is no common structural history inherited: all components de novo produced. The most important
reasons to exclude viruses from tree of life:
• VIRUSES ARE NOT ALIVE
o lack any form of energy, carbon metabolism
o cannot replicate/evolve by themselves
o produced only within cells + also evolve within cells
o without cells, they are ‘inanimate complex organic matter’
• NO ANCESTRAL LINEAGES
o no gene shared by all viruses identified
o there are common protein motifs in viral capsid likely through horizontal gene
transfer/convergent evolution
• NO STRUCTURE DERIVED FROM COMMON ANCESTOR
o cells obtain membranes from other cells during cell division -> no inherited structure
1
,2. ORIGIN OF VIRUSES
3 traditional scenario’s:
• ‘Primordial virus world’ or ‘virus early’ hypothesis
• ‘Reductive virus origin’ or ‘regression’ hypothesis
• ‘Escaped genes’ hypothesis
è It’s probably chimeric origin
2.1. ‘VIRUS ERALY’ HYOPOTHESIS
• direct descendants of the first replicons that existed during the pre-cellular stage of the evolution of
life
• really old + existed before cells
2.2. ‘REGRESSION’ HYPOTHESIS
• ultimate products of degeneration of ancestral cells -> lost their autonomy -> transitioned to obligate
intracellular parasitism
• remnants of earl cellular life (cellular life was there first)
2.3. ‘ESCAPED GENES’ HYPOTHESIS
• evolved on multiple, independent occasions in different cellular organismsfrom host genes
à acquired capacity for (quasi)autonomous selfish replication + infectivity
• Mothercells evolved and specific genes “escaped” as partciles
2
,2.4. CHIMERIC ORIGIN OF VIRUSES
• truth: is combination of the previous theories
o ss or ds RNA, ss or ds DNA
o Two core modules that > of genes encoding proteins required for genome replication (nsp)
and proteins involved in virion formation (sp)
• Chimeric origin
o replication machinery: from the primordial pool of genetic elements
o structural proteins: from hosts at different stages of evolution
2.5. EVOLUTION OF VIRAL AND CELLULAR REPLICATION MODULES FROM ANCESTRAL RNA
RECOGNITION MOTIF (RRM)
• RNA recognition motive is crucial
• RRM = one of the most common RNA-binding domains + occurs in all forms of cellular life
• Structurally related domains widespread in many viruses + mobile genetic elements
• Also: No close homologues in cellular life à shared by diverse viruses
o exception: RNA dependant RNA polymerase à all RNA viruses have them
o RdRp universally conserved across all RNA viruses
Cellular ancestry of capsids
• Viral capsids have limited diversity
• ~60% of viruses have icosahedral structure
o Other common capsid structures: rod-shaped/filamentous, helical
• Sequence & structure comparison: many capsid proteins evolved from ancestral cellular carbohydrate-
binding or nucleic acid-binding proteins, confering receptor-binding capacity and genome protection
3
, 2.6. KOCH’S POSTULATES
• if diseased organism dies of the disease -> than u should be able to isolate the pathogen and when given
to healthy person -> should get same disease with same symptoms
• 21st century revised version of Koch’s postulates:
o nucleic acid sequence of a supposed pathogen has to be present in most cases of an
infectious disease
§ and should be found preferentially in those organs or gross infected anatomic sites
known + not in unaffected organs.
o fewer/no copies of pathogen-associated nucleic acid sequences in hosts or tissues
without disease.
o resolution of disease -> copy number of pathogen-associated nucleic acid sequences
decrease/ become undetectable
§ oppositie with clinical relapse.
o nature of the microorganism derived from the available sequence ->consistent with known
biological characteristics of that group of organisms.
o sequence detection before infection or sequence copy number correlates with severity of
disease/pathology -> the sequence-disease association causal relationship sequence-based
forms of evidence for microbial causation should be reproducible.
3. CLASSIFICATION OF VIRUSES
• Viral genomes are DNA and RNA based
o RNA genomes appeared first in evolution (RNA World)
o Switch to DNA genomes à bigger!
o Only RNA genomes on the planet today are viral
• Baltimore system
o Viral genomes must make mRNA that can be read by host ribosomes!
§ All viruses on the planet follow this rule, no known exception
• Genome structural diversity
o Nature (RNA or DNA)
o Strandedness (single or double)
o Orientation (- or + or ambisense)
o Topology (linear or circular) of nucleic acids in the virion
o Gapped or segmented
o Nucleotide sequence!
4
1. WHAT ARE VIRUSES?
• most obundant biological entities on earth
• have a high genome evolution rate
• MAJOR role in global ecology + evolution of biosphere
• Obligate intracellular parasites
o -> package their genomes into tiny protein/lipid particles
• biomass wise only small part bc very tiny + min. structures
• All harbour distinctive repertoires of viruses -> eat + breath billions of virus particles
• Human DNA > partly remnants of ancestral viral genetic material
• Diverse in structure
o many are spherical + little/small
o also unusual large viruses (normally they are pretty small)
§ PANDOVIRUS & MIMIVIRUS
§ approach sizes of bacteria
§ viruses also found living on amoeba
1.1. OLBLIGATORY INTRACELLULAR PARASITES
• infect each life form: plants, animals, eukaryotes, bacteria
• DNA or RNA, ss or ds, protein coat, +/- lipid envelope
o protein core surrounded by lipid membrane from ‘host cell’
o naked virus: genetic material w/ protein coat
o enveloped: protein coat + lipid membrane
• Rely on host cell for energy production, protein synthesis and reproduction
o virus code only for a few proteins -> viral proteins gave to interact w/ other proteins
• All viral genomes = obligate molecular parasites -> can only function after replication in cell
• All viruses must make mRNA that can be translated by host ribosomes -> all parasites of the host
protein synthesis machinery
• important disease-causing agents, but not all viruses make us sick
o Many just passengers through body (food intake, breathing)
§ immune system learned to deal with (some) viruses
1.2. RE VIRUSES DEAD, ALIVE OF ANYTHING IN BETWEEN?
There is no common structural history inherited: all components de novo produced. The most important
reasons to exclude viruses from tree of life:
• VIRUSES ARE NOT ALIVE
o lack any form of energy, carbon metabolism
o cannot replicate/evolve by themselves
o produced only within cells + also evolve within cells
o without cells, they are ‘inanimate complex organic matter’
• NO ANCESTRAL LINEAGES
o no gene shared by all viruses identified
o there are common protein motifs in viral capsid likely through horizontal gene
transfer/convergent evolution
• NO STRUCTURE DERIVED FROM COMMON ANCESTOR
o cells obtain membranes from other cells during cell division -> no inherited structure
1
,2. ORIGIN OF VIRUSES
3 traditional scenario’s:
• ‘Primordial virus world’ or ‘virus early’ hypothesis
• ‘Reductive virus origin’ or ‘regression’ hypothesis
• ‘Escaped genes’ hypothesis
è It’s probably chimeric origin
2.1. ‘VIRUS ERALY’ HYOPOTHESIS
• direct descendants of the first replicons that existed during the pre-cellular stage of the evolution of
life
• really old + existed before cells
2.2. ‘REGRESSION’ HYPOTHESIS
• ultimate products of degeneration of ancestral cells -> lost their autonomy -> transitioned to obligate
intracellular parasitism
• remnants of earl cellular life (cellular life was there first)
2.3. ‘ESCAPED GENES’ HYPOTHESIS
• evolved on multiple, independent occasions in different cellular organismsfrom host genes
à acquired capacity for (quasi)autonomous selfish replication + infectivity
• Mothercells evolved and specific genes “escaped” as partciles
2
,2.4. CHIMERIC ORIGIN OF VIRUSES
• truth: is combination of the previous theories
o ss or ds RNA, ss or ds DNA
o Two core modules that > of genes encoding proteins required for genome replication (nsp)
and proteins involved in virion formation (sp)
• Chimeric origin
o replication machinery: from the primordial pool of genetic elements
o structural proteins: from hosts at different stages of evolution
2.5. EVOLUTION OF VIRAL AND CELLULAR REPLICATION MODULES FROM ANCESTRAL RNA
RECOGNITION MOTIF (RRM)
• RNA recognition motive is crucial
• RRM = one of the most common RNA-binding domains + occurs in all forms of cellular life
• Structurally related domains widespread in many viruses + mobile genetic elements
• Also: No close homologues in cellular life à shared by diverse viruses
o exception: RNA dependant RNA polymerase à all RNA viruses have them
o RdRp universally conserved across all RNA viruses
Cellular ancestry of capsids
• Viral capsids have limited diversity
• ~60% of viruses have icosahedral structure
o Other common capsid structures: rod-shaped/filamentous, helical
• Sequence & structure comparison: many capsid proteins evolved from ancestral cellular carbohydrate-
binding or nucleic acid-binding proteins, confering receptor-binding capacity and genome protection
3
, 2.6. KOCH’S POSTULATES
• if diseased organism dies of the disease -> than u should be able to isolate the pathogen and when given
to healthy person -> should get same disease with same symptoms
• 21st century revised version of Koch’s postulates:
o nucleic acid sequence of a supposed pathogen has to be present in most cases of an
infectious disease
§ and should be found preferentially in those organs or gross infected anatomic sites
known + not in unaffected organs.
o fewer/no copies of pathogen-associated nucleic acid sequences in hosts or tissues
without disease.
o resolution of disease -> copy number of pathogen-associated nucleic acid sequences
decrease/ become undetectable
§ oppositie with clinical relapse.
o nature of the microorganism derived from the available sequence ->consistent with known
biological characteristics of that group of organisms.
o sequence detection before infection or sequence copy number correlates with severity of
disease/pathology -> the sequence-disease association causal relationship sequence-based
forms of evidence for microbial causation should be reproducible.
3. CLASSIFICATION OF VIRUSES
• Viral genomes are DNA and RNA based
o RNA genomes appeared first in evolution (RNA World)
o Switch to DNA genomes à bigger!
o Only RNA genomes on the planet today are viral
• Baltimore system
o Viral genomes must make mRNA that can be read by host ribosomes!
§ All viruses on the planet follow this rule, no known exception
• Genome structural diversity
o Nature (RNA or DNA)
o Strandedness (single or double)
o Orientation (- or + or ambisense)
o Topology (linear or circular) of nucleic acids in the virion
o Gapped or segmented
o Nucleotide sequence!
4
