Lecture 8 - Viral Pathogenesis Flashcards
Class 1 replication of virus with DNA genomes
Class I: Double-stranded DNA viruses
- after infection, viral dsDNA enters the host’s nucleus
- mRNA is produced by host’s RNA
polymerases using the dsDNA genome as a template - new dsDNA genome is replicated by host’s DNA polymerase using the dsDNA genome as template (usually in the nucleus)
-used to make more copies, gets packged and exits out the cell
Class 2 replication of virus with DNA genomes
Class II: Single-stranded DNA viruses
- after infection, the ssDNA gets converted to dsDNA as it moves into the host’s nucleus
- mRNA is produced by host’s RNA
polymerase using the ‘dsDNA version’ of the viral genome as a template - new ssDNA genome is replicated by host’s DNA polymerase using using dsDNA
genome as template
-replication cycle is still fairly easy
-single becomes double and then used to transcribe mrna using host RNA poly
Class 3 replication of virus with RNA genomes
ClassIII: Double-stranded RNA viruses
- dsRNA genome has a template strand and a non-template strand, much like dsDNA
- viral particle contains RdRp which gets released in the host’s cytoplasm alongside the dsRNA genome
- mRNA is produced by RdRp using the dsRNA genome as a template
- new dsRNA genome is replicated by RdRp using the dsRNA genome as a template (via ssRNA intermediate)
Class 4 replication of virus with RNA genomes
ClassIV: positive-sense single-stranded
RNA viruses
- ssRNA (+) genome which gets injected into host’s cytoplasm is the mRNA
- ssRNA (+) genome is translated directly by host’s ribosomes, producing viral proteins such as RdRp
- full-length and sub-genomic ssRNA (-)
molecules are produced by RdRP using the ssRNA (+) genome as template - new ssRNA (+) genome as well as sgmRNAs are produced by RdRp using the ssRNA (-) molecules as template
- Artificial transfection of host cell with
just the ssRNA (+) genome still leads to
production of mature virions
Class 5 replication of virus with RNA genomes
Class V: Negative-sense single stranded
RNA viruses
- viral particle contains ssRNA (-) genome plus RdRp, which gets released into host’s cytoplasm
- mRNA is produced by RdRp using the
ssRNA (-) genome as the template - new ssRNA (-) genome is replicated by
RdRP using full-length ssRNA (+) molecules as a template
ssRNA (-) and RdRp go into the cytoplasm
What is common amongst Class 3, 4, & 5 RNA viruses?
ClassIII, IV and V RNA viruses use viral
RNA-dependent RNA polymerases
(RdRp) for replication and mRNA
production
- no DNA intermediates are used for
replication and mRNA producton - replication and mRNA production occurs in cytoplasm
carries their own genome and RdRp into the cytoplasm which prduces all the other RNA
What class is Poxviridae and how does it replicate with DNA genomes?
Members of Poxviridae replicates DNA in host’s cytoplasm
- viral particle contains dsDNA genome plus viral RNA polymerases and transcription factors, which gets
released into host’s cytoplasm - mRNA is produced by viral RNA polymerases (and transcription factors) using the dsDNA genome as
template, in the cytoplasm - therefore Poxviridae is still classified as Class I
- viral mRNAs are translated in the cytoplasm to produce viral more viral proteins such as a viral DNA
polymerase and structural proteins
* new dsDNA viral genome is replicated in the cytoplasm using viral DNA polymerases
What is the viral replication strategy of SARS-CoV -2?
Replication strategy of SARS-CoV-2:
- recognizes host cell using the S-protein
- releases genome into host cytoplasm after membrane fusion
- positive-sense ssRNA genome gets translated directly by
host’s ribosome - generation of RTCs to produce more copies of positivesesnse
ssRNA genome and sub-genomic mRNA via negative-sense ssRNA intermediates - translation of structural proteins and assembly mature
virions
What is the difference between the replication strategies of SARS-CoV 2 and other viruses?
Replication strategies of other viruses follow the same principles, but their exact mechanisms are extremely diverse
- especially for genome-replicating strategies between viruses with different types of genomes
Host cell recognition and entry
Viral particles attach to host cells to
initiate infection
* viral attachment proteins are used to target
receptor proteins on the host cell surface
All viruses have a limited range of
permissive hosts
* in addition, viruses of multicellular
organisms can often only replicate inside
select cell types in the body
Host specificity is typically determined
by the combination of
* viral attachment protein
* host receptor on cell surfaces
- Viral particle (or part of it) enters the
cell following attachment
Enveloped viruses
- entry into cell is mediated by fusion of viral envelope and the plasma membrane (HIV, etc.)
- other enveloped viruses can enter via
endocytosis (influenza, etc.)
Non-enveloped animal viruses
- whole viral particle enters the cell by
endocytosis (rhinoviruses, etc.) - the particle eventually gets disassembled, releasing viral genome in the cytoplasm
Host cell recognition and entry by plant viruses
Plant viruses do not recognize specific
cellular receptors on their host cells
Virions enters the cell through disruptions on the plant cell’s surface
* disruption can be caused by mechanical forces such as farming machinery, animals and insects
feeding, etc.
Plant cells are interconnected by small
channels called plasmodesmata
Newly formed viral particles or viral genomes spread to other cells in the plant through plasmodesmata
Host cell recognition and entry by bacteriophages
Bacteriophages with head/tail morphology
* contacts the host with its tail fibers, holding the tail perpendicular against the cell surface
* genomic material inside the head is injected into the cytoplasm via the tail
Filamentous bacteriophages have specialized attachment proteins at ends of the filament
for viral-host interaction
-bacteriophage attaches to the host cell
envelope using tail fibers.
then the tail grows a pyhiscal
hole into the cytoplasm
Class 6 replication of virus with RNA genome
Class VI: Single-stranded RNA viruses that use reverse
transcriptase
- viral particle contains ssRNA genome plus reverse
transcriptase and an integrase, which gets released into
host’s cytoplasm - reverse transcriptase converts ssRNA genome into the
dsDNA version in the cytoplasm - dsDNA genome moves to the nucleus and becomes part of
host’s chromosome using the integrase - mRNA is produced by host’s RNA polymerases using the
integrated dsDNA genome as the template - new ssRNA genome is replicated by host’s RNA polymerase
using the integrated dsDNA genome as the template
Reverse transcriptase (Retroviruses) and how it is used to replicate RNA viruses (Class 6)
Retrovirus which has integrated into the host’s
chromosome is called a provirus
- Many proviruses in our chromosomes have lost their
infectivity
Our chromosomes have been accumulating remains of
these retroviruses over evolutionary history
5 - 8 percent of our genome could have originated
from retroviral genome integration
What is a provirus
Retrovirus integrated version. a piece of dna is expected to
‘become’ the virus that is why it’s called pro
Reverse transcriptase (Pararetroviruses) and how it is used to replicate DNA viruses (Class 7)
Class VII: Double-stranded DNA viruses that utilize reverse transcriptase
- after infection, viral dsDNA enters the host’s nucleus
- mRNA is produced by host’s RNA polymerases using the dsDNA genome as template
- full-length RNA version of genome is produced by the host’s RNA polymerase
- new dsDNA genome is replicated by a reverse transcriptase using the full-length RNA genome
as the template
What is the difference between mRNA production in Class 1 and 7 DNA viruses?
Class 7 uses reverse transcriptase (pararetroviruses and class 1 does not)
Technically, mRNA production of these viruses are same as Class I dsDNA viruses
- however, the use of reverse transcriptases makes their replication cycle distinct enough to be in
their own class
Replication of bacteriophages
Many bacteriophages have dsDNA genome
or a positive-sense ssRNA genome
* their replication cycle is similar to their
eukaryotic counterparts
What are Virulent phages?
- Virulent phages (lytic phages) always kill
their host after successful infection
What are Temperate phages?
Draw it’s life cycle
Temperate phages may become a non-lytic prophage
- prophage genomes co-exist with the host as a plasmid or as part of the host’s chromosome
- prophages are quiescent (latent) and do not cause cell lysis
- a trigger will eventually cause the prophage to re-enter the lytic cycle, replicating new virions
and lysing host cells
Explain viral assembly and exit
- All viruses must eventually assemble more
viral particles and exit the host cell to
infect more host cells / host individuals - Assembly is an irreversible process
- Some viruses exit by budding out of the
infected cells - Others exit by lysing the infected cell
What does viral transmission refer to?
After the leaving its original host, viral particles must get transmitted to another host for infection and reproduction
Viral transmission is closely related with their replication strategies
For transmission, viral particles must…
- be expelled from the host
- remain infectious until they encounter a new host
- gain access to the appropriate cells within the new host
Characteristics of Rhinoviruses (horizontally transmitted virus)
- family Picornaviridae
- positive-sense ssRNA genome
- icosahedral symmetry, non enveloped
- causative agent of about a third of ‘common cold’
How Rhinoviruses are transmitted and what cells they occur in
Replication occurs in cells of upper respiratory tract
- causes coughing, sneezing and increases nasal secretions
- this allow newly produced viral particles to exit the infected host and contact a new host via aerosolized
droplets or contaminated surfaces
Examples of vertically transmitted viruses (mother to fetus)
- Rubella
- HIV (also sexually transmitted)
- Hepatitis B virus, etc.
Viral particles in blood may be transferred to fetus through
placenta or during birth
Characteristics of HIV (vertically & horizontally transmitted virus)
Human immunodeficiency virus
vertically (mother to fetus)
horizontally (sexually)
- family Retroviridae
- positive-sense RNA genome
- icosahedral symmetry (conical), enveloped
- infects and disables immune cells
- causative agent of acquired immunodeficiency
syndrome (AIDS)
Characteristics of Ebola
(zoonotic transmitted virus)
- family Filoviridae
- negative sense ssRNA genome
- helical symmetry, enveloped, pleomorphic
- causes fever, headache, diarrhea, vomiting and
extensive hemorrhaging (bleeding) - extremely deadly; fatality rate depends on each
outbreak - on average, 50%
- highest fatality rate, 90%
- incidental (dead end) hosts = it cannot persist in our population and eventually becomes
exstinct in our population. ends with us, however we still suffer
Can Ebola be horizontally transmitted?
- Natural reservoir for Ebola are thought to be bats
- Ebola can also be horizontally transmitted through
contact with blood and other body fluids - however, horizontal transmission can not maintain Ebola population within the host, and the outbreak eventually
concludes - every Ebola outbreak is thought to have originated from separate zoonotic transmission event of the virus into human society
Can zoonotic transmitted viruses evolve to horizontal? if so list examples
Some zoonotic viruses have evolved to make (true) horizontal transmission possible
* HIV and SARS-CoV-2 were once zoonotic, but humans
are now their natural host
What is mechanical transmission/vector borne and give 2 examples
Transmission via ‘completely unrelated agent’ between human individuals. For example:
* transfer via medical devices contaminated with infected blood
* transfer via mosquitoes biting infected host, and biting an uninfected host with contaminated mouths
Do viruses replicate in mechanical transmission?
The virus does NOT replicate in mosquitoes or syringes
* these ‘completely unrelated agents’ are merely vectors which
carry the virus from one individual to another
There are viruses which replicate in the insect vector, so the line between this and horizontal / zoonotic
transmission is a bit blurred
* yellow fever virus
What is an infection?
entry of viral particle into a cell
What is abortive infection?
- infection of non-permissive host
- few (if any) new infectious viral particles will be produced
- no viral replication will be successful
What is productive infection?
- more common
- infection of permissive host
- new, infectious viral particles will pe produced, leading to disease
- viral replication, translation and transcription
What is viral pathogenesis caused by?
- direct damage to cells and tissue during viral replication
- immune response of the host to the virus (immune system of the host overreacting, and cause more damage to the host’s own body)
What is viral pathogenesis?
the process of viral infections causing diseases
Viral pathogenesis through direct damage
- Viruses deploy mechanisms to survive and replicate in the host cell
- Viruses inhibit host’s transcription and/or translation
-Viral replication leads to host cell death or compromised function, which typically causes disease symptoms related to the types of affected cells
What mechanisms do viruses deploy to replicate?
- evasion of host cell defenses
- freeing up host resources for viral replication
How do viruses inhibit host’s transcription and/or translation
- inhibit translation of host’s mRNA
- block translation of host’s mRNA (SARS-CoV-2)
- destroy host mRNA
coronaviruses causes ________________ malfunction
respiratory
_____ causes immunosuppression
HIV
it directly attacks and supresses immune cells
Explain Viral pathogenesis through host’s own immune response
In many cases, disease symptoms of viral infections are caused by host’s own immune response rather
than direct damage caused by the virus
Host’s innate and adaptive immune systems can destroy infected cells to purge viral replication
* however, this may also cause damage to surrounding tissue
* immune system must balance these benefits and harms but does not always succeed
Explain Rhinoviruses do viral pathogenesis through host’s immune response
- viral replication in the respiratory tract cause relatively low damage but stimulates elevated levels of proinflammatory cytokines in the area
- cytokines cause vasodialation (widening of blood
vessels), leading to build-up of fluids in upper respiratory
tract, congestion, sneezing, etc.
Explain Ebola virus does viral pathogenesis through host’s immune response
Viral replication stimulates large amounts of proinflammatory cytokines
* may be different from the ones above
These cytokines cause blood vessels to become leaky
* this allows other immune cells to leave the blood
and reach the area of infection
However, the immune response to Ebola is so strong that the tissues becomes too leaky, leading to hemorrhaging
* loss of blood leads to shock and to death
What are the 3 types of viral infections?
acute, latent, and persistent
Acute infection
- infections that have a short duration
- acute infections represent majority of the viral infection which humans experience
examples: rhinoviruses and Ebola virus
Individuals start to show signs of disease
shortly after initial contact
* virus replicates quickly, followed by a delayed, but strong immune response
Shortly after its onset, the disease
concludes because the host:
* clears the infection and recovers, or
* fails to clear the infection and dies
Persistent infections (chronic infections)
- disease condition may not be as severe as acute infections, but the host does not clear the virus in a reasonable amount of time
- continuous production of new viral particles
- virus may dampen the host immune system for long-term survival
- programmed cell death could be repressed to keep infected cells ‘alive’
Latent infections
- acute onset of disease symptoms after initial contact
- after the initial response, the virus enters a latent, non replicating (non-disease causing) phase to coexist
with the host - viral replication resumes after a long duration (even years after infection), causes a diseased state for
a while, and then re-enters the latent phase
Are persistent and latent infections lifelong?
Yes typically
