Viral Structure And Replication Flashcards
Virus size is
Small
Viruses are _____ _____cellular
Obligate intracellular
Viruses don’t have ____
Sub cellular organelles
Viruses can only ____ in living cells because they ___
Replicate
Rely on host cell protein synthesis machinery
Does a virus divide and proliferate
No, new virions are assembled
What is a virus made of
Nucleic acid
Protein shell
Envelope
What does the nuceleic acid provide
Genome
Either DNA or RNA
The genome and enzymes make
Core
What does the protein shell makeup
Capsid
A capsid can be ____ or ____
Helical
Icosahedral
Core + capsid =
Nucleocapsid
Nucleocapsid math
Genome + enzyme = core
Core + capsid = Nucleocapsid
What is the envelope of a virus
Lipid bilayer derived from the host membrane WITH viral encoded glycoproteins
Nucleocapsid aka
Naked capsid virus
Envelope math
Nucleocapsid + glycoproteins and membrane
We use the ___ classification system
Baltimore
Baltimore classification system is based off of
Genome and replication strategy
The ______ dictates replication strategy
Type of Nucleic acid
ssDNA viruses =
Noneveloped —> icosahedral —> PARVOVIRIDAE
How do viruses infect cells
Attachment
Entry/uncoating
Macromolecular synthesis
Assembly and release
MAAE
How does attachment work
Viruses bind and infect
If it can’t bind it is USELESS
How does entry/uncoating work
The genome needs to be released into the cell
What two steps are crucial for the virus to infect
Attachment and entry
How does macro molecular synthesis work
Viral proteins get transcribed/translated
Genome gets replicated!
How does assembly and release work
New viral particles assemble
Released thru lysis or budding
Review the picture as to how viruses infect
9 steps
Week 8
DNA genome can _____ like eukaryotic cells
Persist over time
Where does the DNA virus genome live
In the nucleus
The DNA viruses nucleus can utilize
The hosts cell chromosome
Or
Exist as a separate plasmid thing
DNA viruses can utilize ____ to copy Nucleic acid
Host polymerases
RNA virus has to make its own
Polymerases
RNA dependent RNA polymerase
Which mutates more, why
RNA viruses
Because RNA polymerases make more mistakes, it picks up more point mutations
DNA viruses and retroviruses are more _____ which can cause ___
Stable
Latent infections
Which turns into a cancer cell
DNA viruses and retroviruses
RNA Virus genome key characteristic
Labile/not long lasting/can’t just hang out
RNA virus genome lives where
Cytoplasm
Why do RNA have immune escape variants
They’re not as stable
The variability is changing the antigenicity
Quasi-species
Variability of RNA virus
Think of Quasimodo, he had lots of variable features
Helical vs iscosehedron shape
H= spiral
I = 20 sided shape
No human viruses that are ____ and _____
Naked and helical
Function of a capsid
Protect the genome
Help attachment - proteins on capsid bind to receptors on cell
Help entry/uncoating - capsid needs to fall apart to release genome
Help assembly
Assembly w/o capsid
Not infectious bc there is no genome incorporated
Naked icosahedral virus wet or dry, which means?
Dry = retain infectivity
Naked, icosahedral virus acidic virus or not
Survive acidic conditions of GI bc
A viral particle that is not infectious has ____
No genome in it
Naked, icosahedral viruses in response to temp and detergents
They are resistant to
extreme temps
detergents
poor sewage treatments
How are naked, icosahedral viruses released
Usually by cell lysis
Bc N, Ico are dry that means
Transmits through fomites
And
Really hard to disinfect surfaces
Bc N, Ico survive in acid
This means they can transmit vis fecal/oral route
They are responsible for most cases of viral gastroenteritis
Bc N, Ico released through lysed cells that means they are
Cytopathic
Viral envelope is from
Host cell
The viral envelope includes
Viral encoded glycoproteins
Glycoproteins in the envelope
Matrix proteins
Surface glycoproteins
Matrix proteins helps virus infect through
Assembly
It’s a bridge btw capsid and bilayer
Surface helps virus infect through
Viral attachment
Virus-cell fusion - fusing the bilayers
Antibody????
Envelope virus properties
Must stay wet
Acid and heat labile
Detergents destroy it - respond to disinfecting
Released by budding
The budding of enveloped viruses means
Virus release over extended periods of time
More persistent
Slowly it will kill host off
When N, Ico lyse out of the cell what does it do to the cell
Kills it
Because enveloped viruses must stay wet that means
Transmitted through droplets, secretion, resp, blood, organ transplants
Because enveloped viruses are acid/heat labile
They can live in GI and cant be passed fecal/oral
How do enveloped viruses attach
Surface glycoproteins
How do naked viruses attach
Capsid proteins
____ is key for tropism
Attachment style and viral receptors
What are the different types of viral receptors
Enzymes
Hormone
Cytokine
Complement receptor
Molecules involved in cell-cell interactions
Virus has evolved to take advantage of ____
Host receptors
How do enveloped viruses enter a cell
Fusion event
Describe fusion event
What viruses does it happen to
A hydrophobic domain/fusion peptide on the attachment protein of the virus is EXPOSED after it binds to a receptor on the host cell
Fuses to host cell and releases capsid
ENVELOPED
Describe how N, Ico enters cell
Hydrophobic interactions create a channel through the membrane and the RNA is let into the cytoplasm
pH dependent endocytosis
Involves clathrin proteins
And dynamin
1.Virus enters and turns into endosome
2.Endosome becomes acidic and fuses with lysosome
3.The acidic pH or lysosomal proteases activate fusion activity
pH independent endocytosis
Involves caveolin protein
a lipid raft
1.virus internalized at an invagination with a lipid raft that has caveolin
2.caveolin vesicles fuse with caveosome
3.no lysosomes or acidification involved
4.viral fusion protein active a neutral pH can fuse without acidic environment
What pH do you need to utilize for pH dependent entry?
Depends on the virus. Can utilize high or low pH
Describe endocytosis of N, Ico viruses
- Capsid proteins form a pore through endosomal membrane
- Viral capsid proteins lyse membrane
- Confo Chang in capsid protein
to either
uncoat
or
create a pore
Uncoating means
Release of genome
RNA uncoating is in
Cytoplasm
DNA uncoating is in
Nucleus
Uncoating coincides with entry refers to what kind of virus
RNA
Triggers for uncoating
Binding to a receptor
Change in pH
Proteolytic degration
DNA viruses travel on what to get to the nucleus
MICROTUBLES
dynein
Steps in taking over the host cell
1: control transcription
2: replicate genome
3: control protein synthesis
Early transcripts vs late transcripts
Early: this is allll the stuff you need to shut down the host
late: now you’ve shut down the host, you can encode viral structural proteins
Where does transcription and translation occur in DNA viruses
Nucleus
DNA genome is ____ for mRNA
Template
Most DNA viruses use ______ encoded polymerases to replicate genome
Virally
Most DNA viruses use ______ polymerases to transcribe viral mRNA
Cellular
Positive strand RNA virus genome can function as
MRNA
Positive strand is the equivalent of the ____ strand
Coding
+ strand RNA aka
+ssRNA
What happens after the +ssRNA is dumping into the cell
1: translated to polyprotein
2: cleaved into viral proteins
3: on specific viral protein made is the RNA dependent RNA polymerase (RDRP)
4: the RDRP copies + strand to - strand
5: the - is a template to make more + ssRNA
6: those +ssRNA made turn into viral proteins
or Nucleocapsid
the viral proteins also eventually go to Nucleocapsid
What is located inside the polyprotein
A protease
-ssRNA is the ____ strand
Complement
The - strand is the _____ for mRNA
Template
When the -ssRNA enters a cell what does it need to bring with it
RDRP
What is a core protein and who encodes it
RDRP
Negative strand RNA
When - enters with RDRP what happens next
1: can either make (a)mRNAs or (b)+ssRNA
(A) then they make viral proteins
which then go to nucleoplasmids
(b)they then make more copies of viral genome which then go to nucleoplasmid
A ___ strand copy of the genome is the template for genomic RNA
+
Reoviruses aka
dsRNA
Genome is segmented for
dsRNA
Segmented genome means
Diff proteins on diff pieces of RNA
RDRP is incorporated in
dsRNA and +/- ssRNA
____ strand RNA is transcribed into DNA =
+
Retrovirus
What is the core enzyme in retrovirus
RNA dependent DNA polymerase (RDDP)
____ travels to the nucleus where it integrates into the host cell
Provirus
The DNA provirus of retrovirus goes on to do what
It’s transcribed to make mRNA and genomic RNA
See retrovirus pic
Yub yub
Capsids ____ assemble
Self
____ determine site of budding for _____
Matrix proteins
Enveloped viruses
Viral budding can happen at the ___ or the _____
Plasma membrane or at the ER membrane
Antiviral therapy targets 3 things
Disrupt viral structure
Block virus specific activity
Avoids interfering with host
How does an antiviral disrupt viral structure
Detergents inactivate enveloped virus
How does an antiviral block virus specific activity
Target polymerases(this one is common), proteases, and attachment proteins
Targets steps in replication that only viruses use
Productive vs nonproductive
P: actively making virus particles
permissive
NP: not making viral particles
non permissive
Types of productive infection
Lytic
Persistent/chronic
Persistent with Lytic virus
What kind of infection produces changes to a cell and what is that called
Lytic
Cytopathic effect (CPE)
Virus buds with no lysing
Continual shedding
Chronic/persistent
At tissue or organ
Some cells lysed but not all
Persistent infection with Lytic virus
What are the types of CPE
Syncytial formation
Cell rounding or vacuolization
Inclusion bodies
MEGA cell is what
Syncytia formation = fusion of cytoplasm of adjacent cells making mega cells
Areas within a cell with lots of replication going on. Can be seen on a stain
Inclusion bodies
____ can help clinical virologists identify virus
CPE
Non reproductive infection
Abortive
Latent
Virus is dormant within host cell
Latent infection
_____ occurs in retroviruses or DNA viruses ____ RNA viruses
Latent
NOT
Why can’t our immune system detect latent infection
Bc the cell is not making any viral protein, so there is nothing for us to act on
In latent infection there are _____ for antiviral drugs to act on
No targets
Viral genomes usually integrate into the chromosome in _____ infections
Transforming
Transformed cells are ____
Immortalized
Immortalized cells may or may not become ____
Tumor cells
Mechanism for transforming cells
1: inactivate growth-regulatory proteins
2: provide or up-regulate genes involved in cell progression through the cell cycle
What growth reg proteins does transformation effect
P53
Retinoblastoma gene product
What are some consequences of transformation
Uncontrolled cell growth
Increased growth rate
Alteration of morphology and metabolism
Loss of contact inhibition of growth
just continual divisions
See nice map of viral replication
Yub yub
Acute infection remains ___
Localized
What type of infection is cleared by immune response
Acute
Acute disease leads to
Symptomatic illness
Where do acute infections enter host
Mucosal surfaces
When a host has a subacute / sub clinical infection what does that mean
They are asymptomatic BUT they are still shedding active virus
___ provides protection against actue infection
IgA response
Localized infection starts acute then ____ through _____
Disseminates
Blood
Where do you see symptoms of a localized infection
Replication at the secondary site
A disseminated infection means people are _____ before _____ is recognized
Infectious
Illness
Time period between exposure and symptoms show up
Incubation period
Prodrome
Nonspecific or flu-like symptoms during dissemination
___ is important for immunity of disseminated infections
IgG
Chronic infections could be _____ or ______
Productive or nonproductive
Cellular level vs tissue level productive chronic infections
C = host cell is not destroyed by infection
T = only a few cells in the population are infected at any one time
Non reproductive chronic infection latency vs transformation
L = reactivating of latent virus results in productive infection
T = cells are altered
a person is ___ during ______ but not during ______ or a nonproductive chronic infection
Infectious
Reactivating
Latency
When the cells are altered during nonproductive chronic infection that means they are ____ and not _____
Transforming
Infectious
Latency to deactivation steps
1: primary infection - local or disseminated, symptomatic or asymptomatic
2: latent infection -asymptomatic
3: reactivating - secondary infections cleared more rapidly than primary
Why are reactivated infections cleared more rapidly than priamary
Cuz or our memory in our immune system
Course of infection pic
Yub yub
Getting a disease depends on
Whether or not the pathogen can overwhelm the immune response
Balance between pathogenicity and immune response =
Whether or not you’ll get a disease
Symptoms of a disease are from
Our immune response
Or
Results of virus infecting and killing a cell
Disease pic
Yub yub
Transmission determines
Site of entry
Inoculum size influences
Severity
Tissue tropism determines
Site of pathology
Viral virulence factors =
Mech to control host cell protein synthesis
Mech to evade immune response
Mech to directly damage cells
If you have an acute viral infection you are treating the
Symptoms
Current antivirals do what
Inhibit actively replicating virus, not latent infections
The ____ the better with antivirals because __
Earlier
The viral replication may precede symptoms
Define chemoprophylaxis
Using antiviral to prevent disease from even starting
