Exam Flashcards
Examples of how viruses drive evolution of hosts
Beneficial relationships
- selective advantage - the moths
- HERVS
- molecular negotiations
how has the study of virus replication enhanced our understanding of molecular cell biology
- retroviruses
- hervs
- exploitation (gene therapy etc)
Fundamental differences between viruses and other infectious agents
Virus:
- submicroscopic
- assembly via pre-formed components
- dont grow/divide
- dont encode for metabolis, ribosomes, etc
- rewuire 5 part strategy to infect
principles behind plaque assay
plaque = succesful infection
only shows infectious viruses #
see progression over time
structural features of viral particles
- capsid
- core
- envelope
- spike proteins
Types of capsids
icosahedral
helical
Traits of a capsomere
- icosahedral symmetry
- 20 triangular faces
- 12 vertices
- 11 identical
- 1 special (pore)
Functions of virus envelope
hold spike proteins
- host-range determination
- entry
- assembly // egress
- evasion from immune system
advantages of envelope
have spike proteins
does not lyse cell
types of viral genomes
mRNA
DNA
RNA
expression of + mRNA genome
immediately translatable
expression of dsDNA
—> mRNA
expression of + ssDNA
—> dsDNA —> mRNA
expression of dsRNA
—> mRNA
expression of + RNA
—> -RNA —> mRNA
Expression of -RNA
—> mRNA
expression of +RNA via DNA intermediate
—> -DNA —> dsDNA —> mRNA
how is a single step growth experiment performed
- every cell infected with MOI 10
- absorbed at 4
- Penetrated at 37
- Plaque assay
what step of a plaque assay in energy dependent
penetration
key features of growth curve
eclipse period: absorption —> appearance of infection
latent period: absorption —> release of infection
Steps of infection
- attachment
- penetration
- uncoating
- expression
- replication
- assemble / egress
examples of penetration
- endocytosis
- fusion with cellular membrane
- pH independent ( at cell surface)
- pH dependent (in acidic endosome)
steps of pH dependent penetration
- spike proteins attach viral cell to host
- proteins want to unfold - coil coil interraction
- pH drops
- receptors interract
- protein rearrangement
- membranes attach and seperate
dna vs rna gene expression
DNA
- in nucleus
- need RNA pol 2
RNA
- in cytoplasm
- needs enzymes made
egress: naked vs envelope
naked: lysis + cell death
envelope: budding
how can histological detection of virus assemble be used to diagnose viral diseases
inclusions
what are inclusions
very high [] of capsid proteins in infected cells
detectable via light microscopy
Shared properties of all herpesviruses
- icosaheral
- spikes
- dsDNA
- ABY proteins
- cell death
- inclusions
- latent infections
- close contact transmission
alpha proteins
dna binding proteins
regulation gene expression
beta proteins
enzymes for metabolism + replication
gamma proteins
structural
3 groups of herpesviruses
Gamma
Alpha
Beta
Gamma herpes causes what
EBV - mono
where is latency of gamma herpes
B lymphocytes
what does alpha herpes cause
HSV 1,2, VZV
where is latency of hsv 1 and vzv
peripheral neurons
what does beta herpes cause
HCMV
where is latency of beta herpes
monocytes and lymphotyes
where is beta herpes replicated
kidney and secretory glands
Herpes absorbtion
4 glycoprotein receptors
envelope fuses w plasma membrane
tegument proteins enter cell
- VP16 = transcription factor for alpha genes
- Ribonuclease cuts host RNA to stop host replication
Capsid + microtubles = transport to nucleus
herpes uncoating and expression
- capsid portal aligns with pore of nucleus
- cannot retain pressure
- genome flys into nucleoplasm
- genome circularizes
- VP16 —> alpha genes —> beta proteins —> concatameric dna —> Y proteins
herpes capsid assemble
- portal forms
- dna pumped into capsid
- protease activate — removes scaffolding
what is a b capsid
scafolding not removed, no genome
what is an a capsid
scafolding removed
support not added in time
can’t withstand preasure
empty
herpes envelopment and egress
- nuclear regress
- capsid buds into nuclear membrane = perinuclear membrane capsid = PRIMARY ENVELOPMENT
- deenvelopment = in cytoplasm
- incorporated into particles
a) tegamund binds to proteins
b) secondary envelopment
- buds into trans-golgi network
- fuses with plasma membrane
- deenvelops into extracellular space
poxvirus replication cycle
- infection
- early mRNA
- translation —> A proteins
- some leave as immunity factors - A proteins = transcription factors —> intermediate mRNA
- intermediate proteins = late transcription factors
- late proteins —> packaged in factory
- envelopes
- exit
a) lysis
b) secondary membrane via budding
how does poxvirus differ from other DNA viruses
- closed ends
poxvirus dna replication
- closed ends dsDNA
- nuclease nicks one end
- hairpins form
- replicated from 3’ to 5’
- repeated to form concatameres
- cleaved into individual genomes
viral pathogenesis
The process of disease by virus in host
determinants
- interaction w target
- lethality (of cells)
- host response
- immunopathology
shoot the target. did you kill it. how did it respond. what symptoms did they have.
viral factors of pathogensis
- dose
- route
- tissue
- genotype
DSTG
dude, swear to god it wasnt me, it was the virus
host factors of pathogensis
- age
- immune status
- genotype
- nutritional status
- otehr infections
**Think questions that a dr would ask
how can viruses infect GI tract
Peyer’s patches
M cells bring virus to patches
Then spreads
modes of dissemination
viremia
- blood to tissue
[ epitheleal cells —> shed into tissue —> can cause hemmoraging]
[transcytosis: across epithelial —> basal membrane]
[diapedesis: through cells]
CNS
- peripheral nerves
- olfactory nerve bodies in nose
- diapedesis
stages of viremia
- passive: initial infection in blood
- primary: infection —> lymphnodes
- secondary: infection —> new tissue + blood
acute infections
**When entire replication cycle completes
rapid onset, rapid resolution
sign of good immune system
Chronic/latent infection
**When complete replpication cycle fails
- long term symptoms
Latent infection
** Replication halts in latent phase within nucleus of certain cells
reactivates from triggers
examples of cytopathic effects from virus
- inhibition of protein synthesis
- damage to cell lysosomes
- change to plasma membranes
- inclusions
- apotsis
apotosis vs necrosis
necrosis
- results from damage to cell
- loss of membrane integrity = death
- inflammation
Apotosis
- programmed cell death from signalling
- no inflammation
Intrinsic immunity
- pre existsing
- first line of defense
examples of intrinsic immunity
- apoptosis
- autophagy/zenophagy
- host reduction factors (SAMHD1)
- Epigenetic transcriptional silencing of vitaal genomes
SAMHD1
- limits availability of dNTPs
- needed in retroviruses for dna intermediate
How can viruses protect against SAMHD1
VPX
- taggs SAMHD1 w ubiquadone
- polymerized
- signalled to proteosome to be degraded
Epigenetic transcriptional silencing of vital genomes (DNA viruses)
- viral genome loaded with histones
- histones make genome compact
- compact = can’t transcribe
How do viruses protect against Epigenetic transcriptional silencing of vital genomes (DNA viruses)
- ICP0 and Us3
- degrade and prevent PML nuclear bodies from folding histones
Innate immune system examples
- cytokines
- sentinel cells
- natural killer cells
- complement
Adaptive immune system examples
- B and T cells
- memory
Explain how type I interferon system works
- Ligand binds receptor on one chain
- both chains come together
- Jax activated
- Phosphorylation of JAX
- Phosphorylate STATs
- STATS form dimer with IRF9
- complex enters nucleus
- Binds to ISRE
- Transcription of ISGs
How does PKR prevent infection
- Binds to dsRNA of virus
- Protein unfolds and phsophorylates self to activate
- dimerizes
- Phosphorylates EIF2alpha to prevent binding of GTP
***stop protein synthesis = apoptosis
How does OAS/RNaseL work to prevent infection
- activated by dsDNA
- activates RNaseL
- degrades cellular mRNAs
- inhibts protein synthesis
- apoptosis
virus mediated inhibition of OAS/RNaseL
RNaseL inhibitor binds to dsRNA so RNaseL can’t
differences between MHCI and MCHII
1:
- expressed on all nucleated cells
- binds endogenous peptides
- Recognized by CD8+ cells
2:
- expressed only on antigen presenting cells
- binds exogenous peptides
- recognized by CD4+
Maturation of MHCii
- antigen enters cell
- proteosome degrades it within endosome
- MHCII leaves ER via invarient chain
- vesicle fuses with endosome
- new vesicle moves to surface
- CD4 helps bind MCHII to CD4 cell
Maturation for MHCI
- MCHI complex formed in ER
- Proteosome cuts up protein into peptides
- Peptide binds to MCHI
- MCHI leave ER to Golgi
- Exits to surface of cell
- CD8 binds MCHI to CD8 cell
how are antibodies produced
- b cell receptors match
- b cell activates
- endocytosis virus
- degrades
- gives peptides to helper cell
- produces cytokines
- cytokines bind receptors on B cell
- JAX SATS initiated
- B cell differentiates
- one b memory and one b lasma
plasma cell created antibodies
how can antibodies work
- neutralization
- opsonization
- antibody dependent cell dependent cytotoxicity
how do viruses inibit surface expression of MHCII
prevent trafficking out of ER
prevent delivery to surface
How can viruses inbhibit NK cell function
Produce false activation receptor
how is poliovirus spread
injected
GI tract
lymphnodes
blood
blood brain barrier
spinal cord
horns
inactivated vs oral polio virus
inactive
- safe for immunicpompromised
- no associated disease
- more exapensive
- dont prevent transmission
oral
- cheaper
- live virus
- can cause paralysis
Acyclovir MOA
- bound to guanine
- no 3’ end
- can’t add any other nucleotides because no 3’ end
pleconaril
stabilizes virus particle + prevents uncoating
physically blocks receptor
hervs
retrovirus remnants in the human genome
8%
How do polydnaviruses aid in the replicative cycle of parasitic
wasps such as Cotesia congregata?
Inject eggs and a virus into worm
virus protects eggs against host immune
Worms dies as eggs hatch
Use nutrients of worm to grow
