CH 6 viruses Flashcards
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Acellular infectious agents
Require a host for replication
- viruses
- viroids
- satellites
- prions
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Archaeal Virus ATV
Infects archaea, replicates, causes cell to lyse, repeat
What’s interesting about this is that the virus is able to add proteins to its protein coat tail outside of its host. This is the first we’ve seen any virus do something like this, though most think that the proteins are made while the virus is still in the cell.
Brings up the question of where do you draw the ling of “living things.” There are some parasites and bacteria that can’t reproduce outside their host, but they’re “alive.”
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Virology
The study of viruses.
Beijerinck (1899): first to discover viruses with the TMV
Rous (1911): discovered viruses can cause cancer; Rous sarcoma virus
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Virion
Complete viral particle. Consists of nucleic acid contained within a protein coat (capsid).
Also called a nucleocapsid.
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Nucleocapsid
Nucleic acid may be DNA or RNA.
Capsid - large macromolecule structure made of protein subunits called protomers.
- single protein subunit or multiple subunits - more proteins = larger genome, where most viruses and viral genomes tend to be very small
- self-assembling
- protects the viral genetic makeup and aids in transfer between host cells
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Protomer
Single protein subunit that makes up a viral capsid.
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Smallest viruses
phi x phage - infects bacteria
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Largest viruses
Mimivirus ~ .25 micrometers. Inhabit amobea. Thought to be the biggest until this summer with the discovery of…
Pandora virus! It’s one micron with a genome of 2-2.5 megabases. Inhabits amobea
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Most viruses are very specific
Most viruses are very specific to the species and type of tissue they inhabit. Rhabo virus (rabies) can cross species, and HIV is another example of a jump across virus
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Major shapes of viral capsids
Helical
Icosohedral
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Helical Capsid
Long, hollow protein tubes.
- TMV (rigid rod structure)
- influenza virus (flexible)
Size depends on the length of the nucleic acid and the size of the protomers.
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Icosohedral Capsid
Sphere shape = large volume = more genetic material
Polyhedron 20 equilateral triangle faces.
Ring-shapes subunits called capsomers that are constructed of 5 or 6 protomers.
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Capsomers
Ring-shaped structure in icosohedral capsid composed of 5 or 6 protomers
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Complex Capsid
Name means it’s a complex structure with both icosohedral and helical elements to its structure.
Require several types of proteins to compose capsid (larger genome).
T-even bacteriophage:
- binal symmetry
- icosohedral-like head
- helical tail
Vaccinia virus
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Viral envelopes
Some viruses only have their protein capsid (“naked”), but others are surrounded by a membrane envelope.
The membrane is derived from host cell
Viral proteins in the membrane - peplomers involved in attaching to next host cell and entering it.
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Peplomers
Viral proteins that the viruses places in the membrane envelope to use to attach to and enter the next host cell.
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Envelope proteins
- Hemagglutinin: binding to host cell
- Neuraminidase: release of the mature virus from the cell; facilitates infection by breaking down mucus. We use these two proteins to type viruses:
- ex. H1N1
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Enzymes within the capsid
Certain enzymes are kept within the capsid, along with the nucleic acid. These enzymes are used for the replication of the viral genome (esp. for RNA viruses). smaller genomes, so don’t make a lot of proteins
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How can we classify viruses?
Capsid shape
Envelope or no
Size
Genome composition
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Genome diversity
Nucleic Acid
Shape
Strandedness
Sense
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Genome diversity: nucleic acid
DNA
RNA
Both DNA and RNA
RNA is more mutable, so can mutate faster
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Viral genome diversity: shape
Linear
Circular
Segmented–multiple pieces, more complex when reproducing
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Viral genome diversity: strandedness
Singl-stranded
Double-stranded
Double-stranded with regions of single-strandedness
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Viral genome diversity: sense
Positive sense: mRNA - can start translating right away
Negative sense: template strand - needs to be transcribed first to the mRNA before translation can occur
Ambisense: parts are positive, parts are negative
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Genome size
Smallest: 3,200 bp (just a couple of genes)
Largest: 2.3x10 6 bp
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Process of viral multiplication
attachment entry synthesis assembly release
- if you can disrupt this pathway at one of these five steps, you can stop the virus from multiplying
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Viral multiplication: attachment
Mediated by receptors
- host selection
- tissue specificity
Interaction between viral proteins (ligands) and host receptor proteins, specificity for type of cell can attach too which limits the tissues can attach too
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Viral multiplication: entry
Different for each type of virus
Bacteriophages: inject nucleic acid directly into the host cell; capsid left outside cell
Eukaryotic viruses:
- fusion of viral envelope with cell membrane - release nucleocapsid into the cytoplasm
- endocytosis - receptor mediated; caveolae and clathrin pathways; nucleocapsid may remain in vesicle or be released into the cytoplasm
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Viral multiplication: synthesis
Express viral genes
Synthesize viral proteins
Replicate nucleic acids
DNA viruses use host enzymes for transcription and translation
RNA viruses require special proteins for replication and mRNA synthesis
- enzymes packaged into nucleocapsid
- encoded by +sense strand
Retroviruses incorporate into the host genome
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Enzymes for viral multiplication
DNA-dependent DNA polymerase
DNA-dependent RNA polymerase
RNA-dependent DNA polymerase (reverse transcriptase)
RNA-dependent RNA polymerase (negative sense strand)
Sometimes the first gene will be the enzyme needed to replicate the genome.
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Retroviruses
RNA viruses use reverse transcriptase to make DNA strand > use host DNA-dependent DNA polymerase to make a second DNA strand (complementary double)
Double strands of DNA get stuck in the host genome.
Ex. HIV
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Regulation of viral protein synthesis
Early genes: involved in taking over the cell
Late genes: coat proteins and packaging proteins
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Viral multiplication: assembly
Auto-assembly of capsid
Insertion of nucleic acid into capsid
May be very simple– helical capsid assembles around nucleic acid as it is being replicated
Or very complex– bacteriophage assembly occurs in multiple steps
Most assemble in the cytoplasm, but some assemble in the nucleus,
if interrupt any steps, can stop infection
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Bacteriophage assembly
Baseplate proteins > baseplate > tube > tube and sheath
Prohead > mature head with the DNA > Whiskers and neck
Tube and sheath + whiskers and neck > colar > tail fiber proteins
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Viral multiplication: release
Couple of different ways:
1) Lyse cell to release all viral particles are once
2) Release individual particles by budding
- formation of envelope
- viral proteins in membrane
- nucleocapsid enveloped by membrane and released 3) Bacteriophage produce lysozyme (break down glycosidic bonds between NAM and NAG polysaccharides)
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Envelope in viral release
Viral proteins inserted into the membrane
Envelope may come from cell membrane, nuclear membrane, Golgi or ER.
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Antiviral Chemotherapy
It can be difficult to come up with medicines that kill the virus without harming the host cells - you want to specifically target viral activities. HIV epidemic pushed for chemo developement
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Pleconaril
Antiviral chemotherapy
Binds to capsid, blocks attachment and release of RNA
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Integrase inhibitors
Antiviral chemotherapy
Block insertion of viral DNA into hose genome - blocks retroviruses
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Reverse Transcriptase inhibitors
Antiviral chemotherapy
Blocks enzyme for reverse transcription - good b/c we don’t have these enzymes–only in virsues
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Nucleotide analogues
Antiviral chemotherapy
Ganciclovir
Terminates the replication of viral DNA - side effects b/c these drugs also affect our DNA replication - idea is that short-term doses will kill the viruses without too much damage to the host.
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Protease inhibitors
Antiviral chemotherapy
Block capsid assembly - again, can affect the host’s protein production - aim is for short-term doses to kill the virus
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Neuramidase inhibitors
Antiviral chemotherapy
Tamiflu
Block release by budding - good b/c it is specific to viruses
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Interferons
Antiviral chemotherapy
Natural compounds secreted by infected cells, trigger defense response that limits viral spread.
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Classification of Bacterial and Archaea viruses based on multiplication cycle
Virulent virus:
- immediately replicated by the host and released
- lyses cell and infects surrounding cells
Temperate virus:
- sets up shop in the cell for a while; two stages (lytic cycle and lysogenic cycle)
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Two stages of temperate viruses
Lytic cycle
- virus is multiplied and released
Lysogenic cycle
- virus remains in the host without destroying it
- integrates into the chromosome (prophage)
Usually some stress on the host cell causes the prophage to exit the bacterial chromosome and enter the lytic cycle.
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Lysogenic conversion
Temperate phage changes the phenotype of the host cell - increase in viral proteins means that the energy and materials the cell would normally use for its own macromolecules are being used up.
Inhibits synthesis of specific cell surface receptors and prevents infection by other viruses.
May give the host pathogenic properties
- ex. Corynebacterium diphtheria - toxin encoded by phage beta
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Advantages of temperate phage
Survival in dormant host.
Survival of host in high multiplicity of infection.
- Virulent phage would destroy host population
- Pathogens tend to become less pathogenic over time so as not to kill off the host population - it’s an example of coevolution - HIV initially killed off people within a year, but now most infected can live normal lifespans.
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Types of Infections in Eukaryotic cells
Acute infection
- like virulent, incorporate and replicate
Latent infection
- like temperate, go int hiding and wait
Chronic
- retroviruses - particles bud off from cell, keeping host alive
Transformation
- forms malignant (cancerous) cells - onco-viruses
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Cytopathic and Cytocidal effects
Inhibition of host DNA, RNA, and protein synthesis
Damange endosomes, releasing hydrolytic enzymes
Viral proteins in membrane trigger attack by immune system
Toxic viral proteins
Viral inclusion bodies disrupt cell structure
Chromosomal disruption by insertion of virus into genome
Malignancy
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Viruses and cancer
Oncoviruses
Integration into the chromosome
Introduce oncogenes (turn on cell division)
Activate proto-oncogenes
Inactivate tumor suppressor proteins
Most viral cancers take a while to show up - taking time to integrate into a large number of cells
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Cultivation of Viruses
Difficult b/c we need host cells, and these cell cultures need very specific environments - even slight changes in pH, temp, salt concentrations, etc. can kill your cultures.
Tissue culture, fertilized eggs (good for vaccine purposes), bacterial cultures, other living organisms (plant viruses in full plants)
Viruses form plagues in the cultures - where cells have died, full of viral particles
Necrotic lesions - plant kills its own cells around the virus to prevent spread of infection
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Viruses that cause cancer
Human Paoilloma Virus–Cervical cancer
Hepatitis Viruses–liver cancer
Epstein Barr Virus–Lymophoma, nasopharyngela cancer
Papilloma viruses–skin cancer
sarcoma herpes virus–kaposi’s sarcoma
retrovirus–hairy cell leukemia
HTLV-1–leukemia in Japan
Merkel cell polyomavirus–merkel cell carcinonma
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Enumerating viruses
Plague Assay
- plague forming units
Hemagglutination assay
Immunoflourescence assay–more virus, more flourescence
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Lethal dose v. infectious dose
Lethal Dose (LD 50 ): dose that kills 50% of host cells or organisms Infectious Dose (ID 50 ): dose that causes an infection in 50% of host cells or organism
