Viruses and Prions Flashcards
Reasons to Study Viruses?
-major source of disease
-limited anti-viral therapies
-One Health
What % of human viral infections have an animal origin?
70%
3 Components of the Definition of a Virus
- Obligate intracellular parasite (needs host cell)
- Submicroscopic (filterable) infectious agent
- Possess genetic material
Viral Small Size Exception
Megavirus from Chile was HUGE (1.2 million base genome)
Viral Genetic Material Exception
prions (do not contain nucleic acids)
Definition of Life
capacity to maintain an electrochemical gradient across a membrane (make ATP)
Are viruses living or non-living?
non-living
Do viruses have any biologically active membranes?
no
Modified Live Virus vs. Inactivated/Killed Virus Vaccine
modified live is still replication content versus killed are chemically inactivated
but NEITHER is living!
Envelope vs. Membrane
an envelope is non-living and does not function metabolically (despite being derived from the host cell)
3 Functions of RNA
- Can fold into complex structures
- Perform enzymatic activities (self-cleaving)
- Contain genetic information
Why is it thought that RNA-based organisms were the first “proto-life” forms?
you can find genes in modern RNA viruses that you can’t find anyplace else - evolutionary remnants
Koch’s Postulates
Polymicrobial Syndromes
“Death by a Thousand Cuts”
you’re not typically chasing after one big deadly virus, but it’s multiple things
The structure and physical composition of a virus provides essential information on what five things?
- Identification
- Pathogenesis
- Diagnosis
- Treatment
- Prevention
identification
how to classify it
pathogenesis
how it causes disease
diagnosis
how to detect it
treatment
how to control it
prevention
how to keep it out
2 Possible Virus Structures
- Non-enveloped
- Enveloped
Layers of a Non-Enveloped Virus
- Protein Capsid
- Nucleic Acid Genome
Layers of an Enveloped Virus
- Lipid envelope
- Protein capsid
- Nucleic Acid Genome
Where do enveloped viruses get their envelope from?
host cell membranes (nuclear, ER, Golgi, plasma)
Whose proteins are embedded in the lipid envelope - host or viral?
BOTH
capsid protein subunits
capsomeres, nucleocapsid proteins, nucleoproteins
Why is a capsid considered a “minimum structure?”
it is made to be the SMALLEST surface area that can encase a MAXIMAL volume
Why does a capsid need to be stable?
protects the nucleic acid genome
Why does a capsid need to be unstable?
it will need to be disassembled to allow the release of nucleic acid during replication
2 Protein Capsid Shapes
- Symmetrical
- Complex
2 Symmetrical Capsids
- Icosahedral
- Helical
Icosahedral Capsid
soccer ball, EPCOT
Helical Capsid
cylindrical with capsomeres arranged in a “spiral staircase” pattern around the genome
ex: rhabdovirus (rabies)
Complex Capsid
no symmetry, an absolute mumbo jumbo or nuclear proteins and nucleic acids
Two Types of Proteins in the Lipid Bilayer of the Virus Envelope
- Surface Glycoproteins
- Integral/Matrix Proteins
Origin of Surface Glycoproteins?
host OR virus
Origin of Matrix Proteins?
viral protein, always
Surface Glycoproteins
glycosylated, often appearing as spikes or protrusions on the envelope
Matrix/Integral Proteins
non-glycosylated viral protein weaves in and out of the envelope to help stabilize it
Budding
process by which the viral envelope is plucked from the host cell membrane and incorporates viral and host cell proteins
Advantages of Enveloped Viruses
- Increased stability to virion
2/ Facilitates entry into cell (lipid-lipid interaction helps promote fusion) - Capsid disassembly
- Incorporation of host cell proteins into envelope gives a level of “camouflage”
Possible Antiviral Drug Target?
hydrogen ion pore
If blocked, then the genome cannot be released into the cytoplasm
Effect of pH on Capsid
a drop in pH causes capsid to fall apart
Amantadine as an Anti-viral
Able to block the M2 H+ pore of the influenza virus
Original goal of Amantadine?
developed in 1966 to treat Parkinson’s by increasing dopamine levels
Do we still use amantadine as an antiviral today?
no - drug resistance developed!
What does amantadine do to pigeons?
Why do we not use antivirals often?
Drug resistance!!!!
4 Classification Categories for Viral Nucleic Acid Genomes
- Nucleic Acid Composition
- Form of Nucleic Acid
- Polarity of ss Genomes
- Structure of Nucleic Acid
Nucleic Acid Composition (2)
- RNA
- DNA
Form of Nucleic Acid (2)
- Single Stranded (ss)
- Double Stranded (ds)
Polarity for ss Genomes
- Positive sense
- Negative sense
Structure of Nucleic Acid (3)
- Linear
- Segmented
- Circular
Positive Sense Polarity
genome can be translated into protein directly
Negative Sense Polarity
complementary copy most be made first
Exception to the rules of virus genome polarity?
retroviruses - positive-sense single-stranded (ss)RNA viruses that replicate through a DNA intermediate via reverse transcription, and integrate into the genome of the host
Prion Discovery
Stanley Pruisner 1982 - PROteinaceous INfectious particles, which were discovered while trying to purify a mysterious virus in sheep (Scrapie)
Examples of Prions
Bovine Spongiform Encephalopathy (Cattle)
Scrapie (Sheep)
Transmissible Mink Encephalopathy (Mink)
Chronic Wasting Disease (Mule Deer, Elk)
Are any species resistant to prions?
yes
5 Important Properties of Prions
- Resistant to heat, UV, and ionizing radiation (also formaldehyde)
- Protein only (NO nucleic acid)
- Transmissible (infectious)
- Filterable (small)
- Slow-acting, aggressive disease
Do prions have a defined morphology?
no, no capsid
What do prion infected brains look like?
Swiss cheese
Can land ever become prion-free?
NO, animals can never be put back on that land
prion incubation period
LONG (take a two year vacation)
PrPc
host-encoded prion, exists naturally, primarily alpha helix conformation
PrPSc
scrapie form, or modified “infectious” form, converted from PrPc; now has primarily beta sheet conformation
Three Ways Prion Conformation Change Occurs
- Spontaneously
- Gene mutation (includes inherited form)
- Infectious (get PrPSc from infected animal)
Which conformation change is arguably the most dangerous?
spontaneous!
there’s no prevention, so you can’t quarantine
prion infection as a self-propagation event
PrPSc binds to normal (PrPc) and converts it to the Scrapie form, acting as a chaperone
Infectious Disease Process of Prions
ingestion of PrPSc
move from intestine to brain via bloodstream or possibly neurons
neurons in brain uptake infectious form, where conversion of PrPc in host begins
no possible removal; accumulates in amyloid-like plaques
sponge-like holes left in brain
Diagnosis of Prion Disease (4)
- Necropsy of brain material
- Propagation Assays
- Antibody-based assays
- Sequencing
Propagation Assays
Limitation of Propagation Assays
takes time!
Antibody-based assays
use unique epitopes on the PrPSc to bind antibody
Is there any evidence of prion resistance?
YES
Fore tribe tradition in Papau New Guinea has a mutation in the PrPc gene making it resistant to conversion to the infectious form of Kuru
Mutation in Fore Tribe is specifically?
conversion of glycine 127 to valine
Which is more susceptible - enveloped or non-enveloped viruses?
enveloped
lipids are much more susceptible to degradation than the capsule; when an envelope disintegrates, the capsid also goes away
Why is species not a commonly used in virus classification?
species technically means it can produce viable offspring, which viruses cannot, they abstain from sexual activity
Current Virus Classification System is maintained by ____________ (ICVT)
International Committee on Viral Taxnomy
Current Virus Classification System (4)
- Presence or absence of envelope
- Capsid symmetry
- Viral genome characteristics
- Nucleotide sequence
Old Methods of Virus Classification (2)
-Host range or disease (mouse hepatitis virus)
-Serological relationship (serotypes)
Virus Order Suffix
-virales
Virus Family Suffix
-viridae
Virus Subfamily Suffix
-virinae
Virus Genus Suffix
-virus
What is used in place of species for viruses (options)?
isolate, strain, group, genotype, serotype, common names
Examples of Virus Classification (just for looking)
these are just for you to look at, don’t panic
and he said to the man, running the stand, “hey, ___________”