Chapter 13 Viruses, Viroids and Prions. Adolf Mayer, 1886 –tobacco mosaic disease (TMD)...
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Transcript of Chapter 13 Viruses, Viroids and Prions. Adolf Mayer, 1886 –tobacco mosaic disease (TMD)...
Chapter 13
Viruses, Viroids and Prions
• Adolf Mayer, 1886– tobacco mosaic disease (TMD) transmissible
• Dimitri Iwanowski, 1892– Filtered sap still caused TMD– contagious fluid or filterable agent
• Walter Reed,1901 – Yellow Fever
• Felix d’Herelle, 1917– Bacteriophage– Suggested phage therapy
• 1930’s, term virus introduced and electron microscopy invented
• Wendell Stanley, 1935 – Isolated tobacco mosaic virus
[INSERT FIGURE 13.4]
• Viral Features – Obligate intracellular pathogen – Host range
• highly specific or generalists
– DNA or RNA – Protein coat– Surface proteins highly susceptible to mutations– Cause synthesis of specialized structures to
transfer viral particles to other cells
• Virion
– complete, fully developed, infectious viral particle– Living or non-living entities?????
• Oldest system based on symptomology• International Committee on Taxonomy of Viruses
(ICTV), 1966– Describe viruses as elementary bio-systems– Classified into orders, families, genera and species
– Over 1,500 officially recognized species
Viral Classification
• 3 primary means of classification:– Nucleic acid
– Replication strategy
– Morphology of protein coat (capsid)
Helical Viruses
Polyhedral Viruses
• Viral Envelope– Acquired from host cell– Phospholipids and proteins– Some glycoproteins are virally coded spikes – Often play role in host recognition
Critical Swine Flu prevention tip:
Don't DO this!
Complex Viruses
[INSERT FIGURE 13.5]
Viral Taxonomy
• Order –virales
• Family –viridae
• Genus – virus
• Species– Common names– Subspecies designated by a number
Viral Taxonomy
• Retroviridae– family
– Lentivirus – genus • Human Immunodeficiency Virus– species
• Herpesviridae – Simplexvirus
• Human herpesvirus 1, HHV 2, HHV 3
Isolation and Cultivation of Viruses
• Viruses must be grown in living cells– Cytopathic effects
• Animal viruses may be grown in living animals or in embryonated eggs
• Animal & plants viruses may be grown in cell cultures– Primary cell lines – Continuous cell lines (transformed cells )
• Serological tests– Detect antibodies against viruses in a patient
• Nucleic acids– RFLPs– PCR
Virus Identification
Multiplication of Bacteriophages
• Lytic cycle Phage causes lysis and death of host cell
• Lysogenic cycle Temperate phages incorporate DNA into host DNA (prophage)
• Attachment Phage attaches by tail fibers to host cell
• Penetration Phage lysozyme opens cell wall,
tail sheath contracts to force tail core and DNA into cell
• Biosynthesis Production of phage DNA and proteins
• Maturation Assembly of newly synthesized phage particles
• Release Phage lysozyme breaks cell wall
Lytic Cycle
[INSERT FIGURE 13.8]
One-step Growth Curve
Lysogenic Cycle
• 3 Important results of lysogeny– Immunity to re-infection – Phage conversion– Specialized transduction
Specialized Transduction
Prophage exists in galactose-using host (containing the gal gene).
Phage genome excises, carrying with it the adjacent gal gene from the host.
Phage matures and cell lyses, releasing phage carrying gal gene.
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2
3
Prophage
gal gene
gal gene Bacterial DNA
Galactose-positive donor cell gal gene
Phage infects a cell that cannot utilize galactose (lacking gal gene).
4
Galactose-negative recipient cell
Along with the prophage, the bacterial gal gene becomes integrated into the new host’s DNA.
5
Lysogenic cell can now metabolize galactose.
6
Galactose-positive recombinant cell
• AttachmentViruses attaches to cell membrane• PenetrationBy endocytosis or fusion• Uncoating By viral or host enzymes• Biosynthesis Production of nucleic acid and
proteins• Maturation Nucleic acid and capsid proteins
assemble• Release By budding (enveloped viruses)
or rupture
Multiplication of Animal viruses
• Attachment of animal viruses– Chemical attraction– No tails or tail fibers– Glycoprotein spikes or other attachment molecules
• Replication of Animal Viruses– Biosynthesis
• Each virus requires different strategy depending on its nucleic acid
• DNA viruses often enter the nucleus• RNA viruses typically replicate in cytoplasm• Must consider:
– What serves as template for replication and how mRNA is transcribed
Multiplication of DNA VirusVirion attaches to host cell
Virion penetrates cell and its DNA is uncoated
Viral DNA penetrates host nucleusEarly transcription and translation; enzymes are synthesized
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2
3
DNA
Late transcription; DNA is replicated
4
Late translation; capsid proteins are synthesized
5
Virions mature6
Capsid
Papovavirus
Host cell
DNA
Cytoplasm
Virions are released7
Capsid proteins
mRNA
[INSERT FIGURE 13.13]
Multiplication of RNA Virus
Multiplication of a Retrovirus
Retrovirus penetrates host cell.
Virion penetrates cell and its DNA is uncoated
The new viral DNA is tranported into the host cell’s nucleus and integrated as a provirus. The provirus may divide indefinitely with the host cell DNA.
1
2
3
DNA
Transcription of the provirus may also occur, producing RNA for new retrovirus genomes and RNA that codes for the retrovirus capsid and envelope proteins.
4
Mature retrovirus leaves host cell, acquiring an envelope as it buds out.
5
CapsidReverse transcriptase
Virus Two identical + stands of RNA
DNA of one of the host cell’s chromosomes
Provirus
Host cell
Reverse transcriptase
Viral RNA
RNA
Viral proteins
Identical strands of RNA
• Assembly and release of animal viruses• Most DNA viruses assemble in and are released
from nucleus into cytosol• Most RNA viruses develop solely in cytoplasm• Enveloped viruses cause persistent infections• Naked viruses are released by exocytosis or may
cause lysis and death of host cell
• Oncogenes transform normal cells into tumor cells– Activated by mutagenic chemicals, radiation, viruses – Causes increased growth, loss of contact inhibition – Cells tend to be misshapen and exhibit chromosomal
abnormalities
Viruses and Cancer
•Oncoviruses•Viral DNA integrated into host DNA•Induces tumors
• Oncogenic DNA Viruses– Adenoviridae– Herpesviridae– Poxviridae– Papovaviridae– Hepadnaviridae
Oncogenic Viruses
• Oncogenic RNA viruses– Retroviridae
• DNA• HTLV 1• HTLV 2
• Latent Viral Infections– Virus remains dormant in asymptomatic host cell
for long periods• Cold sores, shingles
• Persistent Viral Infections– Disease progresses slowly over a long period,
generally fatal• Subacute sclerosing panencephalitis
(measles virus)
• Plant Viruses– Plant viruses
enter through wounds or via biting insects
– May be transmitted in pollen
• Viroids– infectious naked
RNA
Potato Spindle Tuber Viroid
• Proteinaceous infectious particle• Inherited and transmissible diseases• Spongiform encephalopathies
– Sheep scrapie, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, mad cow disease
Prions
PrPC, normal cellular prion proteinPrPSc, scrapie protein
[INSERT FIGURE 13.23]
scrapie proteins accumulate in brain cells forming large vacuoles