○ The endosymbiont poc-like virus had no

Virus–Host Coevolution with a Focus on Animal and possibility for lytic cycle, thus it stated to
Human DNA Viruses replicate by means of cell-to-cell fusion
○ When 2 such cells (infected by related
Virus virus) fused to each other, viral DNA
was copied, and homologous viral
● Obligatory cellular parasites, developing with chromosomes formed tetrads
their hosts ● Cell division resulted in 4 daughter cells with one
● Coevolution copy of the endosymbiont virus in each
○ when the virus and the host affect each ○ Might be the origin of meiotic cell
other’s evolution division
● Red Queen Hypothesis Theory ● After its development, ​sexual reproduction
○ both the parasite and the host are offered a significant fitness advantage against
perpetually struggling to maintain any parasite
constant fitness level
Escaped Genes
Origin of Viruses: 3 Hypothesis ○ Mobile genetic elements escaped the cell
○ These elements acquired a protein capsid and
Primordial Virus World
started to replicate autonomously
○ Homologies can be observed among viral and
● Ancestors of viruses existed already in the
cellular genes
pre-cellular world
○ Root position and direction of evolution is
● Pre-cellular and pre-viral organisms competed
challenging to determine
with each other
■ E.g. cell and viral DNA polymerase are
● Evolution of viruses destroyed the possible
related but direction of viral DNA
signal of genetic relatedness
transfer is unknown
● Evidence:
Cellular Regression Theory
○ Existence of viral protein fold
○ Least favored theory
superfamilies without cellular
○ Viral genome is the remnant of a
counterparts
reduced cellular genome and capsid is
○ Proteins without any primary sequence
the cell membrane
homology are still grouped based on
○ Nucleo-cytoplasmic large DNA viruses
tertiary structure
(NCLDVs)
■ (e.g. the major capsid proteins
■ Proliferate in the cytoplasm
of PRD1 bacteriophage,
■ Have particle and genome sizes
adenoviruses, some archaeal
comparable to the small
viruses all have double jelly fold
prokaryotes
structure)
○ Modern version of the theory
○ Structural homologies in RNA- and
■ Viruses might be the reduced
DNA-dependent polymerases
descendants of pre-cellular
● Examples without cellular homologues:
Ur-organisms
○ Viral RNA-dependent RNA polymerase
■ Convert into obligatory cellular
are not homologous to their cellular
parasites
counterparts
● Viruses became obligatory parasites ​either​:
Viral Genetic Elements in Host Genomes
○ After the emergence of the last universal
● Polintons
common ancestor
○ Also known as Mavericks
○ They were already parasitizing on other
○ Mobile genetic elements with multiple
ancient replicators
homologues in the cellular and viral
● Viral eukaryogenesis hypothesis
genomes
○ Eukaryotic cell nucleus originated from
○ Have escaped several times and gave
an infection by a coated virus (became
rise to different viruses and mobile
an endosymbiont)
genetic elements
 ■ E.g. adenoviruses,
mitochondrial linear plasmids
○ These genetic elements are
homologous and related​, but direction of
genetic exchange is unknown
■ Common from host to virus and
vice versa
● Endogenous Viral Elements (EVEs)
○ Viral genes or complete genomes
inserted into host genomes
○ Most of the elements are of retroviral
origin, other virus families were also
detected
■ Hepadnaviruses
■ Adeno-associated viruses
■ Herpesviruses
○ If insertion occurs in the germ cell line,
then inserted sequence stretch might
get inherited
○ If the insertion provides a selective
advantage (e.g. protection from viral
infection), genomic change will be fixed
○ If advantage disappears, inserted
stretch might mutate over time and lose
its protective nature
○ Important sources for virus-host
coevolutionary research
○ Provide a map for viral host range
○ History of coevolution
■ Detection of homologous
endogenous viral sequences in
different host species
■ Provides information about
historical host range of a virus
clade
■ Can also be inferred based on
● Known diversification
times of the host
● Or phylogenetic
analyses of exo- and
endogenous viral
sequences
● E.g. endogenous
lentiviral sequences in
lemurs are said to be
coevolving with
primates
○ Viruses represent a major force in
evolutionary pressure
■ Retroviruses are effective in
genome integration and
coevolved with vertebrates
● 50% of the human
genome consist
endogenous retroviral
elements
■ In prokaryotes, important
functions were attributed to
integrated viruses
Effects of the Bottleneck Phenomenon
● Reduction of effective pop’n size due to
environmental events, for instance new habitat
colonisation
● Affects the virus-host coevolution: decreases
both genetic variation and the fitness of the virus
● Responsible for the founder effect
● Genetic Drift
○ Changes in genotype frequencies by
stochastic pop’n size reduction
● Occur during both intra- and inter-species steps
of the viral life cycle
● Multipartite viruses
○ E.g. Plant infecting nanoviruses or
animal-infecting bidnaviruses,
alphatetraviruses, nodaviruses and
picobirnaviruses
○ Package their genetic material as
independently encapsidated separate
segments
Antiviral Defence Mechanism
● Shuttled Weapons
○ Superinfection exclusion
■ Integrated and expressed
endogenous viral protein
provides protection from
exogenous infection
■ First described in the tobacco
plant
■ Development was observed in
sheep & koalas
■ Retroviral elements were
endogenous in the genomes of
sheep and koala, providing
protection against certain
exogenous retroviral infections
○ CRISPR-Cas
■ Bacterial antiphage system
■ prokaryotic immune ​system​ that
confers resistance to foreign
genetic elements (google)
○ Argonaute proteins
 ■ Show structural and functional
homologies to retroviral
replication machinery
■ Provide infection against
invading nucleic acids in
prokaryotes
■ Similar with RNA interference
system of eukaryotes (does not
have antiviral effect in
chordates)
○ Endogenous retroviruses
■ Provide transcription factor
binding sites for
interferon-stimulated genes
○ Rag recombinases
■ Originate from transposons
found in genomes of starfish,
oysters, and seas urchins
● Other Mechanisms
○ Antisense RNA
■ Most ancient defense
mechanism
■ Gene translation of invading
pathogen is interfered by small
complementary RNAs
○ Restriction Endonucleases
■ Cleaving the viral genome
○ Piwi-interacting RNA
■ Associate with nucleases and
provide defence against
transposable elements
○ Engagement of pathogen-associated
molecular patterns
■ Induces antiviral cytokines
● Tumour necrosis factor
in eukaryotes
● Interleukins and
interferons in chordates
■ Activates natural killer cells
○ APOBEC3 protein
■ Part of the innate immune
system in humans
■ Targets specifically retroviruses
and interferes with their reverse
transcription
■ HIV counteracts this effect by
the viral infectivity factor
● Triggers the
degradation of
APOBEC3
Adenoviruses
● DNA viruses, major capsid proteins of the
non-enveloped, icosahedral capsid are the
hexon, penton base and protruding fibre,
responsible for receptor binding
● Infect ​vertebrate hosts​ and are clustered into 5
accepted and one proposed genera
● Mastadenovirus and Aviadenovirus
○ Infect mammals and birds respectively
● Atadenoviruses
○ Detected in reptiles, birds and ruminants
and a marsupial possum
○ Were isolated from cattle suggesting
some level of coevolution
● Siadenoviruses
○ In birds, a frog and a tortoise
● Ichtadenovirus
○ White sturgeon adenovirus
● Testadenoviruses
○ Most recently proposed
○ In testudinoid turtles
● Hypothesis started to evolve:​ adenoviruses
started to coevolve with the vertebrates, before
the divergence of fish from other vertebrates
○ Mast-, avi-, at, si- and itchtadenovirus
had been thought to coevolve with
mammals, birds, reptiles, amphibians
and fish respectively
● Thought to be host specific
○ Host changes did happen
○ E.g. 10 predicted host switches in the
evolution of human adenoviruses
■ Presumably a virus strain had
jumped to an ancient ruminant
during evolutionary history
■ Atadenoviruses were isolated
from cattle, sheep and mule
deer, suggesting some level of
coevolution
○ High genomic A + T content contradicts
long cospeciation of these viruses
● Non-reptile atadenovirus genomes have
57-66.3% A + T content, while reptile
atadenoviruses are not affected by such bias
○ It is hypothesized that longer
coevolutionary times---adaptation of the
virus to the host---result in a balanced
nucleotide composition
● Similar observations in pathology
○ Generally cause mild disease and there
are apathogenic strains at least in
healthy individuals
 ○ Not all serotypes of the species ​Fowl
aviadenovirus D and E​ cause inclusion
body hepatitis in chicken
○ Recent host switches might result in an
elevated pathogenicity
○ The A + T content of the known genome
part is over 59% and from serologically
identical strains several fibre size
variants were described
○ Mutations might be consequences of an
ongoing evolution
■ Represent the adaptation to a
new host, cattle
● Most investigated adenoviruses are evidently
human and other primate adenoviruses.
○ Most ancient lineages are the prosimian
and New World monkey adenoviruses
○ Old world monkey adenoviruses and
Human mastadenovirus (HAdV) A, F
and G
○ HAdV-B and -E are of gorilla or
chimpanzee origin respectively
○ HAdV-C seemingly codiverged with
gorillas, chimpanzees, bonobos and
humans
○ HAdV-D viruses infect only humans
● HAdV-D strains show that homologous
recombination has a driving force in adenovirus
evolution
○ Intraspecies recombination events are
common
○ Intergenus recombinatinants have also
been reported
○ Recombination enables an accelerated
modular evolution of viruses
Herpesviruses (HVs)
● Large (150-200 nm) icosahedral, enveloped
viruses with a tegument layer between capsid
and envelope
● Have linear, non-segmented DNA genome
● Known to infect all classes of vertebrates
● Also discovered in mollusc species
● Tentatively classified under the family
Herpesviridae​ because of their morphological
features
● Herpesviridae w ​ as divided into 3 families in
2009
○ Herpesviridae
■ Only the HVs of amniotes
○ Alloherpesviridae
■ HVs of amphibians and fish
○ Malacoherpesviridae
■ HVs of molluscs
● Putative ATPase subunit of terminase
○ Most conserved gene of all known HVs
○ Responsible for packaging of viral DNA
in the capsid
● HVs were also found in T4 bacteriophages
(​Myoviridae​)
● Phylogenetic relationship is largely synchronous
with host lineages, except for mammals
● Major sublineages (​Alpha-, Beta-,
Gammaherpesvirinae​) emerged before
mammalian radiation (60-80M years ago)
● Subfamilies were found 200M years ago
● Bovine herpesvirus 4 ​ (BoHV-4)
○ Isolated from cattle and this species was
thought to be the original host of the
virus
○ Reported from wild buffalo and other
ruminants as well
○ Original host might be the African
buffalo
● Herpesviridae
○ Primate cytomegalovirus genomes also
showed coevolution of virus and host
○ Avian and reptilian HVs
■ Clustered into subfamily
Alphaherpesvirinae
● Alloherpesviridae
○ Fish and amphibian HVs are put within
the order ​Herpesvirales
○ Separation of the main alloherpesvirus
lineages does not fully resemble that of
the host taxa
■ Explanation: Diversion of the
ancestry of the viruses occurred
before the separation of fish
lineages
○ Strong similarity among viruses of
distantly related fish species could be
explained by host switches
● Integrated herpesviral genomes in host
chromosomes were discovered in the last years
○ Discovery of a new lineage of
alloherpesviruses associated with at
least 15 different fish species
■ Salmo salar (​ full-length viral
genome in salmon)
○ HV genome integrated into the genome
of invertebrate chordates
■ Links ancestors of mollusc and
vertebrate HVs
 ■ Branchiostoma floridae g ​ enome ■ Triggered the ​“fourth domain
(Florida lancelet/amphioxus) hypothesis”
shows homology to herpesviral ■ Giant viruses evolved from
genes cellular ancestors
● Terminase and ○ Multiple origin of viral gigantism
polymerase gene ■ Alternative hypothesis
sequences is highly ■ Three major branches on the
similar to the mollusc NCLDV tree
HV ■ At least three independent
emergences from smaller
Nucleo-cytoplasmic Large DNA Viruses (NCLDV) viruses
● Group of DNA viruses including families ○ For translation-related genes
○ Ascoviridae ■ Kinship between viral and
○ Asfarviridae eukaryotic lineages from
○ Iridoviridae phylogenetic analyses
○ Marseilleviridae ● Lateral gene transfers
○ Mimiviridae at different points of the
○ Pithoviridae virus evolution
○ Phycodnaviridae ● Further evolutionary
○ Poxviridae reconstructions reveal a
● Megavirales connection between
○ A new virus order that was proposed NCLDVs and smaller
○ Not yet accepted by the International eukaryotic viruses
Committee on Taxonomy of Viruses ● Derived from tailless
(ICTV) bacteriophages
● Hosts ranges from unicellular eukaryotes via ● Reconstructed phylogeny:
arthropods to vertebrates (mammals included) ○ Branch 1 (Real giants)
● Replicate within the cytoplasm of infected cells ■ Mimiviridae
○ Some families include a nuclear stage ■ Pandoraviruses
● Encode many genes required for a successful ○ Branch 2 (Varying genome sizes)
replication but uses the translational material of ■ Ascoviridae
the host ■ Iridoviridae
● Form a monophyletic group with a common ■ Marseilleviridae
ancestor ■ Pithoviridae
● First giant amoeba virus ○ Branch 3 (Non-giants)
○ Large compared to a normal virus size ■ Asfarviridae
(700 nm) ● African swine fever
○ Has a large genome virus
○ Contained several genes of distant ● Other protist-infecting
origins acquired by lateral gene transfer relatives
● Mimivirus ■ Poxviridae
○ Discovered in 2003 ● Host switch took place
○ Found to contain nearly all NCLDV core two times here
genes ● Coevolution took place
○ Clustered phylogenetically with which caused several
phycodnaviruses genera and poxvirus
○ An oversized NCLDV ‘types’
○ Translation system illustrated a ● Infected a wide range of
divergent evolutionary path arthropods and
○ Clustered on a distinct branch and vertebrates
separated from the three domains of cell ● Second host switch
life happened in sensu lato
asfarviruses
 ○ Infected protists
and pigs
● Phylogenetic reconstructions of NCLDVs
showed a turbulent evolution
○ Dominated by gene gain
○ Substantial gene loss was shown in
other branches
■ Giant protist viruses (gene
gainers)
■ NCLDV animal infectors (gene
loss by gene contraction)
● Hypothesis: selective
pressure for virus
genome size is stronger
than in protists
Polyomaviruses (PyVs)
● Non-enveloped icosahedral DNA tumour viruses
with a double-stranded circular DNA genome
● Polyomaviridae
○ Approximately 80 accepted Py V
species
○ 4 genera: (Alpha, Beta, Gamma, and
Deltapolyomavirus)
○ Taxonomical classification is based on
genetic distance of the large tumour
antigen
● Circular Py V genome is highly conserved
○ 5-7 genes located on both strands
○ Non-coding region
○ Early coding region contains regulatory
proteins: small and large tumour antigen
○ Late coding region contains genes of
the structural proteins (like major (VP1)
and 2 minor capsid proteins)
○ Non-coding region contains regulatory
elements and transcription promoters
● Known to infect mammals and birds, but uses
viral metagenomics
○ Also identified in fish and arthropods
● Py Vs have been coevolving with their shots for
about half billion years
○ Current taxonomic classification does
not reflect this coevolution
○ Some modern Py V species arose after
ancient recombination events
○ Mammalian Py Vs are known to be
host-specific and coevolving with their
hosts
○ Py Vs are generally apathogenic in
humans but not all (e.g. Merkel cell
polyomavirus is oncogenic)
● Intra-host molecular evolution
○ Also a feature of some Py V infections in
humans
○ Mutations in early region can lead to
expression of a truncated form of the
large tumour antigen
● Rearrangements in non-coding control region in
point mutations in VP1 have been described in 2
important human PyVs:
○ JCPy V
■ Mutations lead to development
of progressive multifocal
leukoencephalopathy
○ BKPy V
■ Non-coding control region
rearrangements play a direct
role in the development of Py V
associated nephropathy
○ Therefore, intra-host viral evolution
appears to be an essential component
to the disease process
● A recent host switch is usually associated with
elevated pathogenic
○ E.g. Closely related Py Vs can be
detected in healthy bats, whereas the
goose hemorrhagic polyomavirus infects
geese, Muscovy ducks & murlards
Circoviruses
● Circoviridae
● Vertebrate -infecting single stranded DNA
(ssDNA) viruses with one of the smallest virus
genomes
○ Contains 2 genes (rep and cap)
encoding replication-associated (Rep)
and the capsid (Cap) proteins
○ Porcine circovirus 1
■ First recognised circovirus
infecting swine and wild boar
● Potential long-term adaptation of some
circovirus groups to birds, mammals, reptiles
and fish
● Complete or partial circovirus genome might be
integrated into the host genome as an EVE
○ Rep- and cap- homologues have been
detected in different animal genomes
○ Various possible functions (e.g. antiviral
protection)
● Theories:
○ Plant-infecting geminiviruses as the
ancestors of both nanoviruses and
circoviruses
○ Plant-infecting nanovirus had switched
to a herbivorous vertebrate first, and
 then recombined with a picorna-like
virus via retrotransposable element or a
retrovirus
■ Homologues of the ssDNA virus
Rep were described in plasmids
of eubacteria and algae
○ Close phylogenetic relatedness of
several circoviruses replicating in
various host species may be the sign of
cross-species transmissions
● The common presence of the highly conserved
Rep and the mechanism of the rolling circle
replication are the most obvious evidence for
common ancestry of ssDNA virus taxa and
ssDNA molecules