Lecture 2: After The Midterm Flashcards
Viruses
- Acellular infectious particles
* Obligate intracellular pathogens
What does, “Acellular infectious particles” mean?
non-living, goes into a cell & creates a +/- = parasitic relationship (virus benefits & host cell doesn’t), v. small but it’s there
What does, “Obligate intracellular pathogens” mean?
Reproduce ONLY INSIDE of living cells
• LACK independent metabolism
–>NOT free-living
has an obligation to be in the boundaries of the cell, in order to actually execute viral replication, within the cell, that it has an obligation to be within the boundaries of the cell, in order to execute viral replication, & is disease causing
Are viruses free-living?
O - lack independent metabolism
think: on desk you put sugar, lipids, iron, sodium, water, potassium - anything that’s needed for a living cell to thrive, & then you put virus on top (cough SARS-COV 2 on top of that pile of nutrient for ex), you would NOT get SARS-COV 2 replication (not able to), b/c it doesn’t have the machinery & enzymes for glycolysis & TCA cycle or for fermentation, it doesn’t have ribosomes to protein assembly –> therefore lacking independent metabolism & are therefore NOT free-living
- they’re only able to make more of themselves, if they’re inside of a living cell that provides them with machinery in order to be able to do so
- the virus itself couldn’t infect you, but on the pile on its own don’t expect increase in #
- to contrast, if you put bacteria that were free-living on that pile of nutrients & provided the temp & the pH was within the range for growth, you would def. expect that the # of bacterial cells that fell on that pile of nutrients would now start to increase as a result of growth b/c they do have enzymes for growth, ribosomes for protein syn & can replicate their own nucleic acid, so you can see the diff b/t a virus & a living cell
What are viruses composed of?
- Nucleic acid GENOME (DNA or RNA) and protein coat (CAPSID)
- Together=NUCLEOCAPSID (bare min)
capsid= like a 3d dome, made out of proteins called capsiomeres
nucleic acid= provides recipe for whatever the virus knows it needs to make on its own, bc host cells provide everything else “only pack what they need
Give ex of DNA and RNA virus
(DNA or RNA are the recipes to allow for assembly of viral material)
DNA: hepatitis b, HPV, EBV (casues mono) ALWAYS a DNA virus & will NEVER change
RNA: HIV, Covid, Influenza ALWAYS a RNA virus & will NEVER change
Naked virus
has genome
capsid- made out of capsiomeres
; collectively nucleocapsid
spike proteins; embedded on outer surface of capsid for the naked virus
* UNIQUE VIRAL CHARACTERISTIC AS IS CAPSOMERES
Will they find info in YOUR cell to build their capsid protein or to build their spike protein? If not, where is the recipe to make spike protein & capsid protein
NO - it will be on their DNA or RNA
Envelope virus
Some viruses have an envelope – layer of lipid surrounding the nucleocapsid
takes time to build an envelope on the outside of the structure & that’s where the spike protein will get embedded or inserted b/c that’s now the outermost layer
nucleocapsid + envelope
*ENVELOPE IS AQUIRED FROM THE PM WHEN THE VIRUS LEAVES YOUR CELL
Comparison of naked & enveloped virus particles
Naked:
- Nucleocapsid: nucleic acid & capsid (composed of capsomeres)
Enveloped:
- Nucleocapsid: nucleic acid & capsid
- Envelope
what will this envelope be structurally v. similar to?
- it would look exactly like a PM b/c that’s where it came from - BUT it is NOT a PM
- b/c a PM surrounds a living cell creating the boundaries of that cell
- the PM is also gonna provide selective permeability & this envelope does none of that - it’s just an outer layer that it picked up in the process that it uses to leave your cell
- needs it for infectivity b/c that’s where its spike proteins are & spike proteins are critical for infectivity
Anything that disturbs this envelope, disturbs ____
INFECTIVITY
- Covid, HIV, influenza are ENVELOPE VIRUSES
- so any chemical disinfectant that you use that would disrupt a lipid bilayer like a PM will disrupt this envelope, & when it does you lose it, which took the spike protein that were needed for infectivity
Which type of virus do you think is more hardy, & which type of virus is more challenging to get rid of when you use chemical disinfectants & things like it?
NAKED VIRUS are HARDER to get rid of - b/c they don’t have an envelope to disturb
- LAST LONGER when you use chemical disinfectant & not all disinfectants will work against them
ENVELOPED virus is EASIER to get rid of by comparison
Viral Genome
• DNA or RNA- NEVER both
- a virus that’s an RNA virus today, is a RNA virus always (doesn’t change)
- living cells always have DNA as a component of the cell material
• Single stranded OR double stranded
- we only have ds nucleic acid, but viruses get an option
- HIV, covid, influenza are ssRNA
- HPV is DNA virus
• Circular OR linear (ss or ds)
- if circular & ds - comparable to bacterial chromosome
- if linear & ds - comparable to us
• Can be in several pieces – SEGMENTED
- min. amount of waste virus will have on the cell
- Genome size (complexity varies)
- Smallest ~ 3.6 kb for some ssRNA viruses (3 genes)
- Largest > 150 kbp for some dsDNA viruses (> 100 genes)
DNA viruses have the capacity to…
cause cancer (some of them) - b/c their going into the nucleus, interferring with normal cellular activity, they can upset cellular respiration & these processes to make the cell become a danger inside the body
The type of their _____ can play a role in what that virus’ capabilities will be
nucleic acid
Non-segmented viral genome
everything in a line
- b/c it’s all together - you need to make 1000 of all
INCREDIABLY wasteful - using our cell to do this
- more parasitic to the cell if you’re being excessively wasteful beyond your need
Segmented viral genome
influenza has 8 pieces of RNA that constitutes its genome
- each gene gets its own segment
- so you can make what’s needed - NOT being excessively wasteful
BUT you have to package virus into a new viral particle, so it can exit the cell
How will a segmented genome might have more problems than a non-segmented genome?
have to take ALL the pieces with you
think: backpack with everything - grab & go (NON-segmented)
wallet, keys, sunglasses, book etc - SEGMENTED –> increase chance you’ll leave something behind by mistake & then don’t have that to help me for whatever you needed it to do can be detrimental
Capsid
PROTEIN COAT that SURROUNDS the GENOME
- structure that’s part of the nucleocapsid, therefore EVERY SINGLE virus is going to get 1
- compartment where you can pack genetic material into, so you can transfer the viral genome from 1 host cell to another
Made of identical polypeptides – protomers
Helical capsids
- Protomers form a spiral cylinder
- Nucleic acid genome coiled inside
- Ex. Tobacco mosaic virus capsid is made of ~ 2100 identical protomers
Tobacco mosaic virus capsid is made of ~ 2100 identical protomers, what does it mean for the number copy units for other enzymes?
you will need same number, 2100 of everything if non segmented
Icosahedral capsids
Regular geometric shape with 20 triangular faces
- Exhibit symmetry
- Protomers aggregate to form capsomeres
- Ex. Human papillomaviruses have form their capsids from pentamers (clusters of 5)
polyhedral capsid arrangement
many
protomers
make capsomere which polymerizes to make capsid
Binal capids
Geometric head with an attached helical tail
- Ex. T4 bacteriophage of E. coli; targeting bacterial cells
- Genome is carried in a polyhedral head, helical tail is used to inject DNA into a host cell
lands on surface of cell and inserts genetic material into the cell while rest of structure stays outside
Nucleocytoplasmic large DNA viruses
Viruses with complex multi-layered structure
• Ex. Mimivirus (infects amoebae)
• 0.75 μm in diameter, 1200 kbp DNA
•
• Larger than some bacteria
Nucleocytoplasmic large DNA viruses
• Envelope
a lipid bilayer surrounding the nucleocapsid that was acquired from the host membrane
has spike proteins embedded
* if you use chemical disinfectant that distrubs envelope spike proteins are gone, virus lost its key to get into cell
spike proteins are like a….
key
The envelope consists of….
Consists of host lipids and viral proteins – spikes
A host cell gets infected with a virus
once the spike proteins have been trafficked the virus will push out and take with it the envelope which was portion of PM of cell meaning it will also take with it the spike proteins and you own proteins bc its your cells PM its taking
What challenge could it pose to you if virus inside of you had its own proteins and your proteins inside of it?
your immune system is confused bc spike proteins don’t belong but the glut transporter does so its unsure what to kill allowing for immune invasion
Influenza virus
Flexible helical capsid, surrounded by an envelope
• Two major spikes: hemaglutanin (H)= key used to turn the deadbolt
neuraminidase (N)
How does influenza enter the cell?
hemagluttanin; key used to turn the deadbolt
which attaches to sialic acid on our respiratory cells; deadbolt
What role do the neuraminidase (N) spikes play?
The virus goes into the cell using sialic acid (dead bolt) when its leaving it buds out but the cell its leaving from has sialic acid on the surface so it will want to stick to it bc of attraction between hemagglutinin and sialic acid so neuraminidase (N) allows it to peel itself off the surface of the cell it has already infected so it can go and infect other cells
What can viruses infect
ALL living things- but need key
Bacteriophage (phage)
viruses that
infect bacteria
• Ex) T4 Phage – infects E. coli
Animal viruses
infect and multiply only inside of animal cells
Most viruses are
to a single host species
What must viruses attach to?
must attach to specific receptors on the host cell surface
HIV
Ex) HIV binds to CD4
• Chemoreceptor on surface of some human
immune system cells
• HIV infects only humans
• Some viruses infect
more than one species
• Ex) Influenza attaches to a glycoprotein found on
surface of several animal cells
• Infects humans, pigs, chickens, seals etc.
List the steps of the viral cycle
- Adsorption
- Penetration and uncoating
- Synthesis of viral nucleic acids and protein
- Assembly of new virions
Release of new virions
Adsorption
attachment to the host cell
• Involves specific receptors on the host cell surface
• Ex) LPS, outer membrane proteins or glycoproteins
Penetration and uncoating
entry into the host cell
• Bacteriophage – usually inject their nucleic acid into the cell
• Leave the capsid outside the cell as a “ghost”
How do animal viruses enter
Fusion with the plasma membrane • Endocytosis • Binding to specific receptors triggers normal endocytic activity • In either case, once inside: • The capsid is removed • Viral genome is released into the cell
Synthesis of viral nucleic acids and protein
• Viral genes are expressed and viral proteins are synthesized (by the host’s
own ribosomes)
• Viral genome is replicated (by the host’s replication machinery)
Assembly of new virions
Viral proteins are assembled into capsids, and then genomes are packaged
into nucleocapsids
• Virusesdonotreproducebydivision
Release of new virions
Two basic strategies:
i. Naked viruses usually accumulate, eventually lysing the host cell to release progeny – lytic infection
ii. Enveloped viruses are usually released by budding
• Virions push through the cytoplasmic membrane without killing the host cell – persistent infection
Budding
elease of enveloped viruses
•
Viral proteins inserted into the host membrane – Spikes
• Nucleocapsidassociateswiththespikes,andbudsthroughthe membrane to form the envelope
