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CHAPTER 10
Adenovirus
Definitions of the virus:

Explant cultures of human
adenoids degenerated
spontaneously, isolated a new virus
named adenovirus.

Adenovirus is the etiological agent
of infectious canine hepatitis.
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Definitions of the virus:

The family Adenoviridae comprises
(1) Mastadenovirus: infect mammalian species.
(2) Aviadenovirus: infect birds.
(3) Atadenovirus: infect broad host range.
(4) Siadenovirus: frog, turkey, raptors,
budgerigars, and tortoises.
(5) Adenovirus of fish: white sturgeon
adenovirus
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
Antigenic determinants associated with
the inner part of hexons-structural units
make up the bulk of the capsid; Hexons
involved in neutralization and
hemagglutination.

Genus-specific antigen: the basal surface
of the penton; serotype-specific antigen:
the outward-facing surface of the hexon.
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
Non-enveloped, precisely hexagonal in
outline, with icosahedral symmetry, 70-90
nm in diameter.

Virions are composed of 252 capsomers:
240 hexons that occupy the faces and
edges of the 20 equilateral triangular
facets of the icosahedron and 12 pentons
that occupy the verticles.

A penton fiber 9-77.5 nm in length, with a
terminal knob.
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
The viral genome encodes approximately 40
proteins that are transcribed after complex
RNA splicing.

About one-third of the proteins are
structural proteins, including a virusencoded cysteine protease necessary for
processing of some precursor proteins.

Adenoviruses agglutinate red blood cells,
with hemagglutination occurring when the
tips of penton fibers bind to cellular
receptors and form bridges between cells.
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
Adenovirus replicate in the nucleus, and
their replication is facilitated by extensive
modulation of the host immune response.

Viruses bind to host-cell receptors via their
fiber knots and internalization is mediated
by the interaction between the penton base
and cellular integrins.

The genome is transcribed by cellular RNA
polymerase II involving both DNA strands.
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
Five early (E) transcriptional units (E1A, E1B, E2,
E3, and E4), two intermediate units (IX and IVa2),
and one late (L) unit from which five families of
late mRNA (L1 to L5) are transcribed.

Each early region is controlled by a separate
promoter, whereas the late region uses the
major late promoter.

The E1A region encodes proteins for (1)
induction of cell-cycle progression to provide
an environment for virus replication; (2)
protection of infected cells from cytokineinduced apoptosis; (3) synthesis of viral
proteins necessary for viral DNA replication.
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
E1A and E1B proteins inactivate the cellular
tumor suppresser gene, p53, and thus
deregulate cell-cycle progression.

Inactivation is mediated by ubiquitination of p53
and other proteins through virus-assembled E3
ligases, leading to proteasome-mediated
degradation.

Inhibition of class I MHC antigen transport by
E3/19K inhibits recognition of infected cells by
cytotoxic T lymphocytes and NK cells.

E3/14.7K blocked TNF alpha receptor and
inhibited NF-κB transcriptional activity.
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
Viral DNA replication, using 5’-linked 55K
protein as primer, proceeds from both ends by a
strand-displacement mechanism. After DNA
replication, late mRNAs are transcribed; these
are translated into structural proteins.

The primary transcript is about 29 kb; at least 18
distinct mRNA are produced by alternative
splicing.

Many adenoviruses cause severe condensation
and margination of the host-cell chromatin,
making nuclei appear abnormal (inclusion
bodies).
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Papillomaviridae
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Definitions of the virus:

Papillomaviruses are the cause of
papillomas (warts).

Papillomaviruses can not yet be
grown in conventional cell cultures,
but their genome readily be
sequenced.
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Definitions of the virus:

Papillomaviruses are ubiquitous, but
individual viruses are host-species
specific.

Pathogenic papillomavirus infections
occur with some frequency in
psittacine birds.
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
The papillomaviridae family includes
viruses with circular doublestranded DNA genomes.

There is little sequence homology
between the genomes of
papillomaviruses from different
species.
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
The papillomaviridae family includes
viruses with circular double-
stranded DNA genomes.

Bovine papillomaviruses are
genetically divergent. In dogs,
papillomaviruses are the cause of
epithelial plaques and papillomas of
the skin and mucosal lining of the
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of the oral cavity, conjunctiva, and
external genitalia.

Papillomavirus virions are non-
enveloped, spherical, 55 nm in
diameter, with icosahedral
symmetry.

The genome consists of a single
molecule of circular doublestranded DNA, 6.4-8.4 kb.
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
The genome encodes 8-10 proteins,
two of which (L1 and L2) form the
capsid. The E1-E8 are non-structural
proteins which exert regulatory and
replicative functions.

Papillomaviruses are resistant to
environmental insults.
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
Replication is linked to the growth
and differentiation of stratified
squamous epithelium of the skin
and mucous membranes.

Actively dividing basal cells in the
stratum germinativum are infected
initially, and the virus is maintained
in a proviral, latent state .
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
Virus-induced hyperplasia (early
virus gene products) leads to
increased basal cell division and
delayed maturation of cells in
stratum spinosum and granulosum.

Late viral genes encoding capsid
proteins in stratum spinosum and
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and virions appear at this stage of
cellular differentiation.

The heparan sulfate proteoglycan
and syndecan-3 can serve as a
human papillomavirus receptor on
dendritic cells.

Transcription of early and late
coding region is controlled by
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separate promoters and occurs on
the same DNA strand.

First, the half of the genome (the
early genes) is transcribed to form
mRNAs that direct the synthesis of
enzymes involved in virus
replication and cell regulation.

Late mRNAs that direct the
synthesis of the structural proteins
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(L1 and L2) involved in capsid
assembly which are transcribed
from the other half of the viral
genome.

The regulated expression of the late
(L1 and L2) proteins occurs only in
differentiated epithelial cells or in
differentiating keratinocytes.
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
DNA replication begins at a single
unique origin of replication (ori) and
proceeds bidirectionally on the
circular DNA.

An initiation complex binds to the
origin and unwinds a region;
nascent DNA chains are formed, one
strand being synthesized
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
DNA replication begins at a single
unique origin of replication (ori) and
proceeds bidirectionally on the
circular DNA.

An initiation complex binds to the
origin and unwinds a region;
nascent DNA chains are formed, one
strand being synthesized
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continuously in the direction of
unwinding, the other synthesized
discontiously in the opposite
direction.


It encodes a specific viral helicase.
Virions are assembled in the
nucleus and are released on cell
death, a consequence of cellular
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obsolescence. A infected cell may
produce 10000 to 100000 virions.

E6 protein is a key component
which is a transcriptional activator,
and interacts with and inhibits or
degrades a variety of cellular
proteins, including the transcription
activator, CBP/p300 and p53 tumor
suppressor.
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
It interacts with activating protein 1
in trans-Golgi processes, and it
blocks the activity of paxillin, that
contributes to focal adhesions
between cells.

The host immune response to
papillomavirus infection is directed
against the virus, affording
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protective immunity to subsequent
infection, and against the virusinduced tumor, resulting in
regression of the papilloma or
fibropapilloma.

Once an animal is immune to virus
or has undergone tumor regression,
it is strongly resistant to reinfection,
but it is virus-strain specific.
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Polyomaviridae
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Definitions of the virus:

Polyomaviruses have highly
restricted host ranges, and these
viruses typically cause life-long,
inapparent infections in their
respective hosts.

The family Polyomaviridae contains
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Definitions of the virus:

Polyomaviruses have highly
restricted host ranges, and these
viruses typically cause life-long,
inapparent infections in their
respective hosts.

The family Polyomaviridae contains a
single genus, Polyomavirus.
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Definitions of the virus:

The genome organization, virion
structure, and replication strategy of
polyomaviruses is generally similar
to that of papillomviruses.

Virions and the genome (5 kb) are
smaller than those of
papillomaviruses.
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Definitions of the virus:

The transcription of coding regions
occurs on opposite DNA strands in
polyomaviruses and on the same
strand with papillomaviruses.

Polyomaviruses regulate the cell
cycle and transform infected cells
through their non-structural proteins.
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Definitions of the virus:

Transformation of infected cells
occurs by specific inactivation of the
cellular p53 tumor suppressor gene.

Reactivation of persistent, latent
polyomavirus infections occurs as a
consequence of immunosuppression,
potentially as a result of mutations in
the transcriptional control region.
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