L14 - GL Smith - Consequences of viral infection Flashcards
describe how negative strand ssRNA replicates.
RNA-dependent RNA polymerase encoded by the virus converts -ve mRNA to mRNA
replicaction and transcription occur (producing more -ve mRNA to be put into new vesicles
-ve ssRNA - is purified virus RNA infectious?
no
regarding -ve strnad ssRNA:
Most of these viruses replicate in the _____, but __________ _______ replicates in the nucleus.
Most of these viruses replicate in the cytoplasm, but influenza virus replicates in the nucleus.
describe how influenza is a unique -ve sense ssRNA strand.
it requires host DNA-dependent RNA polymerase II as well as the virus RNA polymerase to make virus mRNAs
describe +ve strand ssRNA viral replication
genome = mRNA
- translation - to yield RNA dependand RNa polymerase
- repliacets genome via -ve RNA (which is then copied again
is purified viral RNA infectious if introduced into a susceptible cell?
yes
redcribe retroviruses’ replication
- genome = +ve ssRNA
- copied by reverse transcriptase to dsDNA
- integrated into host genome
- mRNA transcribed by host DNa dependant polymerase II
labe
in retrovirusess - where does the original reverse trancriptase come from?
in packaged weithin the vesciel
describe how dsDNA viruses replicate?
- in nucleus
- genome transported into nucleus
- Transcription uses host DNA- dependent RNA polymerase II.
for ds DNA viruses - is there a nuclease present in the viral particle?
what does this mean for infectivity?
no nucleic acid polymerase.
if the viral DNA makes its way to the nucleus - replication will occur
The viral DNA alone is infectious.
whihc dsDNA viruses replicate in the cytoplasm?
describe temporal control for viral gene expression
describe quantitative control for viral gene expression
how do +ve ssRNA express thier proteins from 1 RNA?
# translate genome = giant polypeptide proteolytic cleavage - cuts it up into the final proteins
The ______ single mRNA must encode all virus proteins. How? Translate the mRNA into a single giant polypeptide (a ‘polyprotein’) that is post-translationally cleaved by proteases into several, smaller, mature polypeptides.
The poliovirus single mRNA must encode all virus proteins. How? Translate the mRNA into a single giant polypeptide (a ‘polyprotein’) that is post-translationally cleaved by proteases into several, smaller, mature polypeptides.
do retroviruses also use polyprotein processing?
yes - to produce their mature capsid proteins from a polyprotein that is translated from a single mRNA.
Post translational cleavage of large polypeptides into smaller individual proteins is an important feature of many viruses - particularly ______ viruses.
Post translational cleavage of large polypeptides into smaller individual proteins is an important feature of many viruses - particularly RNA viruses.
host or virus codes for proteases responsible for polyprotein cleavage
often virus encoded = chemotherapy targets
does influenza use poly protein cleavage?
a genome with several different RNA segments, each encoding a different polypeptide (e.g., influenza).
do retroviruses also use splicing?
yep
Retroviruses use splicing to place the coding region for some proteins at the mRNA 5’ end. Thus ribosomes select this as they scan the mRNA from the 5’ end.
dewscribe how retrovriuses also use ribosomal frameshifting
describe how virions are assembled
- The assembly of virus protein and nucleic acid into infectious virus particles
- Marks the end of the eclipse phase
- Can be spontaneous: tobacco mosaic virus (TMV)
- Or be complex with multiple stages, e.g. assembly of capsid, insertion of genome into capsid and release +/- envelope
- Can occur at cell surface, or internally
- May require cleavage of a capsid protein
describe the process of viral release
Budding
lysis
cell fusion
what is meant in temrs of latency - viruses
Some viruses can remain quiescent within the infected cell, called latency.
A latently-infected cell contains _________ but no virus ________ occurs, yet the cell has the potential to produce progeny virus - i.e., to switch from latency to the productive replication cycle.
A latently-infected cell contains the viral genome but no virus multiplication occurs, yet the cell has the potential to produce progeny virus - i.e., to switch from latency to the productive replication cycle.
2 examples of latent infections?
retroviruses and herpesviruses:
describe latent infections in retroviruses
dsDNA integrated into host
not transcribed - no proteins expressed
cannot be cleared by immune system
can give rise to verticle transmission
are retroviruses important for evolution?
yep - lots of retroviruses and retrotransposons make up our DNA.
Example: syncytin-2, protein derived from a retrovirus 25-20 mYa that have become essential for placenta formation and so the reproduction of mammals.
describe letent infection in herpes virus
DNA enters nucleus
does not integrate - is not transcribed
and is an extrachromosomal circular molecule called an episome.
not transcribed until changes - meaning cell transcription facotrs recognise viral promoters = transcription
The switch from latent infection to productive cycle is called _____
The switch from latent infection to productive cycle is called reactivation
give examples of herpes virus giving latent infections
- herpes simplex virus (HSV-1) causes repeated cold sores
- varicella-zoster virus (VZV) primary infection causes chicken pox, reactivation causes shingles
- Both HSV and VZV establish latent infection in neurones
give 8 wyas viruses modify cells to tehir advantage
• Subversion of cellular biochemistry to make only virus macromolecules
- Stimulation of host cell metabolism
- Expression of virus enzymes to increase dNTP pools – enhances virus nucleic acid synthesis
- Alteration to host cell membranes
- Morphological changes (cytopathic effect – cpe)
• Suppression of innate immune response
- Persistent (non-lytic) infection
- Cell transformation - cancer
describe how viruses modify cells by subversion of cell metabolism
- shut down host cell protein synthesis
- but viral synthesis continues
- Ribosomes recognise host mRNAs by binding to methylated 5’-cap.
- Poliovirus encodes a protease that cleaves a component of the cap-binding complex so capped mRNAs are not translated.
- Poliovirus RNA has a secondary structure near the 5’ end, called an internal ribosome entry site (IRES)
- This is detected by ribosomes independent of a cap-binding complex. So poliovirus RNA is translated in a cap- independent manner while host protein synthesis is inhibited.
IRES label
describe how viruses stimulate the host cell
other than simulating cell growth - how can viruses increase the nucleotide pool size>
express enzymes which produce dNTPs
Larger DNA viruses (poxviruses and herpesviruses) encode enzymes of this sort: for instance, thymidine kinase, thymidylate kinase and ribonucleotide reductase.
describe the difference between essential and non-essential viral genes
essentail: neeeded for viral replication and growth - eg capsid proteins / virla polymerases
non-essential: improve viral replication - not necessary - eg enzymes for increasing dNTP pools
describe how viruses can modify cells at the membrane sufcae?
advantage of spreading by cell fusion
no extracellular phase - no antibody contact
known as cell-associated viruses
Measles virus can be spread around the body in the form of infected cells.
describe the Cytopathic effect (cpe)
classic morphology of virally infected cells
Rounded, more refractile, motile, alterations to cytoskeleton actin and tubulin
Viruses use cell cytoskeleton (actin and microtubule) to move around and between cells
how can viruses use cytockeleton?
facilitate intracellular movement of virus particles
distinct types of CPE in…
Rabies virus:
Human cytomegalovirus:”
Poxviruses:
Rabies virus: Negri bodies in Purkinje cells in cerebellum
Human cytomegalovirus: nuclear inclusion bodies that resemble “owl eyes”
Poxviruses: cytoplasmic, eosinophilic inclusion bodies
can virally infected cells move?
yep - helps spread virions
label the CPEs
describe how viruses can Suppres host innate immune signalling pathways
Large DNA viruses, such as herpesviruses and poxviruses, encode many proteins that block the innate immune response to infection.
in viral infection does the host cell always die?
no
The productive cycle of DNA viruses is _____.
Non-enveloped RNA viruses are _____.
Viruses that cause host shut-off are _____.
some enveloped retroviruses are _______
The productive cycle of DNA viruses is lytic.
Non-enveloped RNA viruses are lytic.
Viruses that cause host shut-off are lytic.
retroviruses - some8* = non-lytic = continued release of viral particles
what is meant by cell transformation?
Transformation means that the cell now exhibits uncontrolled growth, fails to respond to the presence of neighbouring cells (contact inhibition), and has many of the properties associated with malignant cells in vivo.
can viruses cause cancer>?
yep0
2 general mechanisms viruses cause cancer?
Transformation by certain DNA viruses.
Transformation by retroviruses.
describe transformation by certain DNA viruses?
In the case of certain human papilloma viruses (HPVs) (notably HPV strains 16 and 18) _____ _____ may result.
In the case of certain human papilloma viruses (HPVs) (notably HPV strains 16 and 18) cervical carcinoma may result.
describe viral Transformation by retroviruses.
- aquisition of a host oncogene - this gene is expressed at higher quantities with viral proteins
- RSV aquires src
- Provirus integration into, or adjacent to, a cellular gene that regulates cell division: may lead to inactivation or dysregulation of that gene
Retroviruses expressing such a cellular oncogene (eg src) are called …
Retroviruses expressing such a cellular oncogene are called acute transforming retroviruses.
why do acute transforming retroviruses struggle alone?
Often the acquisition of host gene is accompanied by loss of virus sequences.
Acute transforming retroviruses are therefore usually replication defective and require co-infection by a helper virus to replicate.
RSV lacks the envelope gene (env) and cannot replicate unless a helper virus provides this.
is transofrmation a rare event?
yep
Persistent virus infections lead to cancer: examples….
Herpesviruses: Epstein-Barr virus and Kaposi sarcoma herpes virus (HHV-8)
Papillomaviruses: HPV 16 and HPV 18
Retrovirus: human T-lymphotropic virus 1 (HTLV-1)
Hepadnavirus: hepatitis B virus
Flavivirus: hepatitis C virus
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