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Structural Virology
Lecture 4
Pavel Plevka
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Assembly and exit of virions from cells
1. Attachment
2. Entry
3. Transcription
4. Translation
5. Genome replication
6. Assembly
7. Exit
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Assembly of helical viruses
Tobacco mosaic virus
(TMV)
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Effects of pH and ionic strength on formation
of TMV capsid protein aggregates
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TMV initiation of assembly
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TMV assembly (GMO tobacco)
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Assembly of icosahedral viruses
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Picornavirus assembly
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Adenovirus assembly
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dsDNA virus genome packaging
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Herpesvirus portal structure
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Podoviridae phage assembly
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T4assembly
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Acquisition of a virion envelope by budding
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Complementation of enveloped viruses
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HIV assembly and maturation
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Retrovirus budding
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Assembly and maturation of dengue virus
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Structure of alphavirus
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Structure of iridovirus
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Summary of virus membrane acquisition
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• describe the assembly mechanisms for
nucleocapsids with (a) helical symmetry and
(b) icosahedral symmetry
• discuss the origins of internal virion
membranes and of virion envelopes
• explain the roles played by membrane/matrix
proteins in the budding of some enveloped
viruses
• describe mechanisms used by viruses to exit
from cells
Learning outcomes
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Outcomes of virus infection for the host
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Outcomes of virus infection for the host
Reasons for non-productive infection:
- latent infection
- abortive infection
Persistent infections:
- productive (HIV)
- latent (herpesviruses)
Factors affecting outcomes of infection:
- host immune system
- “quality” of the virus (mutations, suitable host)
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Innate immunity
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Components of innate immunity
- Complement
- Interferons
- Natural Killer (NK) cells
- APOBEC3 protein complex
- tetherin
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Activation and regulation of complement system
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Complement effector system
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Interferon action
Interferon effects:
Alpha and beta
- activation of expression of
antiviral proteins: dsRNA
dependent protein kinase R;
tetherin
- production of MHC I and
proteasome components
(presentation of peptides for
control by T cells)
- activation of NK cells
- induction of apoptosis
Gamma
- produced by cells of immune
system
- activation of phagocytes and NK
cells
Many viruses inhibit production of
interferons in infected cells.
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Activities of Natural Killer (NK) cells
Recognize infected cells
Use perforins to kill cells
Induce apoptosis
Many viruses produce proteins or
microRNAs that reduce response to
NK cells.
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APOBEC3 proteins
Vif protein of HIV induces
degradation of APOBEC3.
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Tetherin
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Adaptive immunity
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Antibody structure
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Antibody structures
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Production of virus-specific antibodies
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Antiviral effects of antibodies
• Neutrophils and macrophages have IgG Fc
receptors -> phagocytosis of infected cells and
induction of apoptosis
• NK cells have IgG Fc receptors -> killing of infected
cells.
• Antibodies can induce genome release from
virions (poliovirus, EV71).
• Prevention of receptor binding
• Release of virions attached to cells
• Inhibition of cell entry (fusion proteins)
• Inhibition of genome uncoating
• Activation of complement
Neutralization of viruses by antibodies
E18 Fab E19 Fab
Control50nm
Electron density levels
(arbitrary units)
E18 E19
E18 Fab E19 Fab
Electron density levels
(arbitrary units)
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Recognition and killing of infected cell by
cytotoxic T-cell
Helper T cells
Cytotoxic T cells (MHC I)
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RNA silencing
• Fragmenting of dsRNA by
DICER (production of 21-
25bp fragments with 2-3nt
3’ overhangs)
• Activation of RISC (RNA –
induced silencing complex)
• Destruction of mRNAs
Many plant viruses produce proteins
that inhibit RNA silencing.
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Maintenance of genomes during latent infection
Retroviruses
Polyoviruses,
Papillomaviruses
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Signals that induce activation of latent infections
• A eukaryotic host cell moves into another phase of
the cell cycle
• The host cell is irradiated with ultra-violet light.
(phages, herpes simplex virus)
• A host organism becomes immunocompromised.
(herpes simplex virus)
• The host cell becomes infected with a second virus
that provides a function that the first virus lacks.
(satellite virus and helper virus)
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Productive infections in plants
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Disease
Virulence of a virus strain
Dose of virus
Effectiveness of immune system (age, nutritional
status, previous training)
Human interventions
Virus elimination x latent infections
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• describe the major components of innate and
adaptive immunity in vertebrates
• outline the process of RNA silencing
• explain programmed cell death
• explain the terms
◦ productive infection
◦ non-productive infection
◦ latent infection
◦ abortive infection
◦ defective virus
• discuss the spread of virus infections within animal
bodies and within plants
• discuss the factors that determine whether virus
infection results in disease
Learning outcomes
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Virus classification
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Phyogenetics trees
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Nomenclature
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(David) Baltimore virus
classification
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• evaluate the traditional criteria used to classify
viruses into families and genera
• write family and genus names in the correct
format
• explain how genome sequence data are used to
classify viruses
• evaluate phylogenetic trees
• explain the basis of the Baltimore classification
of viruses
Learning outcomes
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Herpesviruses
John B. Carter and Venetia A. Saunders
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Figures
Chapter 11
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Latent infection
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