Viruses Flashcards
Define a virus.
a nucleoprotein complex that infects cells and uses the cells’ metabolic processes to replicate
no metabolic activity outside the host cell
highly species specific
What is the difference between naked and enveloped viruses?
enveloped viruses have an envelope in addition to the capsid, naked viruses do not
this envelope facilitates entry into host cells but since this envelope is derived from host membrane that means it is more susceptible to environmental conditions
naked viruses rely on direct cell to cell contact for transmission
What is the difference between single stranded positive sense and single stranded negative sense RNA?
+sense = coding strand, acts like mRNA and can be translated directly
-sense = template strand, must be transcribed into mRNA
What is the simplified process of the virus lifecycle?
- binding to cell surface receptors
- entry
- uncoating
- replication
- transcription
- translation
- virion assembly
- release
What receptors does HIV bind to?
CD4+
coreceptors are CCR5 (macrophage) and CXCR4 (T cells), both transmembrane proteins
What receptors does influenza recognise and bind to?
sialic acid
Avian and Human influenza prefer different sialic acid isomers -> species barrier
What mechanisms does a virus use to enter a host cell?
- endocytosis
- fusion of virus envelope w cell membrane
Once it has entered the host cell how is the virus uncoated?
cell enzymes (lysosomes) strip off virus protein coat
virion can no longer be detected, ‘eclipse period’
Where does virion assembly take place?
nucleus, cytoplasm or at plasma membrane (most common w enveloped viruses)
How are virions released from the cell?
i. sudden rupture of cell (non-envelope viruses)
ii. gradual extrusion (budding) of enveloped viruses through the cell membrane
iii. may occur together w assembly
What are polyproteins and why does poliovirus produce them?
polyproteins are v large proteins encoded by entire RNA genome which are proteolytically cleaved at certain sites in the poly proteins
this is because eukaryotic cells do not encode for more than one protein on each RNA
How does influenza produce variation in the proteins it produces?
it has a segmented genome, 8 short strands each of which can be alternatively spliced to produce different proteins (i think the mRNA is spliced together?)
How do coronaviruses produce variation in the proteins it produces?
they use multiple transcripts, the length of the genome replicated determines the protein made
What are some methods which anti-viral drugs use to inhibit viruses?
- attachment antagonists
- inhibit uncoating
- inhibit DNA/RNA synthesis
- block maturation
What are the routes of transmission viruses can take?
- horizontal transmission
- direct contact
- respiratory
- etc - vertical transmission
- mother to fetus
When can transmission of viruses occur?
- during asymptomatic shedding of virus
- during incubation period
Define acute, chronic, and latent infections.
acute - a short-lived infection that occurs when a virus rapidly replicates in the host’s cells (days/weeks)
chronic - a long-lasting infection that occurs when a virus persists in the host’s body for an extended period, often for months or years
latent - when a virus infects a host and remains dormant or inactive in the host’s cells for an extended period of time
What is a cytopathic effect?
morphological, functional, or structural alterations to cells during viral infection
- translation shut off
- apoptosis
- immortalisation of cell (tumours)
-syncitia formation
-plaques (holes in mono layer of cells caused by necrotic effect of virus)
-inclusion bodies (virus production centre in cytoplasm, eg in rabies)
What is the mechanism of cancer-causing HPVs to disrupt the cell cycle?
E6 and E7 genes mediate destruction of the tumour suppression proteins p53 and PRB respectively
What are interferons?
small molecules produced in response to virus infection
major role in the inhibition of virus infection in cells
does this by inducing an antiviral state in neighbouring cells
What is a cytokine storm?
feedback loop caused by damage of cell produces more and more cytokines causing an overreaction of the innate system which can have adverse effects
Give an example of a PRR that is common during infection of a cell by a virus?
detection of nucleic acid in the cytoplasm and endosomes (only there due to virus)
What are some immune modulation strategies used by viruses?
- secreted modulators
eg cytokine/chemokine mimics and binders - modulators on infected cell surface
eg mimics/antagonists of immune signalling - stealth/Latency
eg express few/ no proteins - antigenic hypervariability
eg HIV, influenza - block adaptive immune response
- inhibit complement system
- interfere with PRRs
- Block interferon and/or inflammatory cytokines
Viral capsid properties?
Protect Nucleic acids
Aid in transfer to host
Can be polyhedral or helical
Made up of capsomere subunits
Glycoprotein spikes?
Present on envelope surface
Bind to cell receptors and facilitate entry and release
How are viruses categorised?
1.Nucleic acid sequence (most important)
2.Nucleic acid type
3.Envelope present?
4.Helical vs icosahedrons symmetry
What sense is mRNA?
+sense
Common method for culturing viruses?
Growing them in chicken egg
Different membranes for different viruses
Quantifying viruses?
Plaque assay
Serial dilutions plated
Areas of clearing on plate represent a single infection event (similar to counting bacterial CFUs)
What is Adsorption?
Attachment of virus to host cell
Randomly collided with correct receptor
Specific proteins on viral surface interact with target cell membrane receptors
Not all cells carrying this receptor can be productively infected as other factors may need to be present (eg certain TFs)
Some viruses need >1 receptor
Tropism?
Host range
The limited cell type spectrum that a virus can infect
What do most neutralising antibodies target on viruses?
Virion attachment proteins
Influenza entry and uncoating methods?
Enveloped virus
Low pH in endosome - conformation change in virus HA (Haemagglutinin, a fusion protein)
Acts similarly to a SNARE protein (neurotransmitter vesicles) to bring the membranes together and fuse them
Poliovirus entry and uncoating strategy?
Non-enveloped, naked virus
Taken into endosome
Causes conformational changes to structure proteins
Causes pore to form in endosome membrane
RNA releases through pore into cystoplasm
How do nerve infecting cells traverse axon?
Energy dependent travel along microtubules
Travel retrograde to reach nucleus
Then travel anterograde to to surface to release - symptoms shown then
viral Budding?
Virus cell exit strategy
Nucleocapsid interacts w viral glycoproteins on cell membrane to form the envelope around the capsid and budd off the membrane
when is HIV infectious?
Only after maturation driven by Virion protease
What are the Nucleic acid polymerases used by viruses?
-DNA dependent DNA polymerase
-DNA dependent RNA polymerase
-RNA dependent RNA polymerase
-RNA dependent DNA polymerase (reverse transcriptase)
Some viruses use the DNA dependent RNA polymerase present in cells
All RNA viruses need to encode RNA dependent RNA polymerase, not present in eukaryotes
dsDNA genome?
Enter nucleus (except pox), needed host enzymes are there
Make mRNA and more dsDNA from genome
ssDNA genome?
Needs to convert ss to ds
ds used to make protein
Then converted to ss form for packaging
dsRNA genome?
Retroviridae
+sense strand used as mRNA to make viral proteins and more dsRNA
ssRNA genome?
+sense genome can be directly used as mRNA
Also used as template for -sense RNA which is used as a template for more +sense RNA (for protein translation and packaging into new viruses)
-sense genome is converted into +sense rna which is used as mRNA and also as a template for more -sense for packaging
Some +sense use a DNA intermediate which integrates into genome
The dsDNA is used as a template for +sense RNA (used as mRNA and for packaging)
How can segmented genomes present evolution opportunities?
2 different strains of a segmented genome virus infect same host at same time
Reassortment of segments in new packaged viruses - kinda like independent assortment of chromosomes - gives new segment combinations
Pigs make good mixing pots as can be infected relatively efficiently by some avian, swine and human strains
Influenza drug targets?
Amatadines block entry and uncoating
Nucleoside analogues block genome replication (targets RNA pol action)
Viremia?
Detectable levels of virus in blood
Secondary viremia can come after secondary round of replication
Summary of Effects of virus on cell?
Apoptosis (cell defence)
Host cell protein translation switch off
Transformation (can cause cell immortalisation)
Strategies of viruses to have their genes translated?
Viral 5’ UTR
Contains IRES, internal ribosome entry site
Acts like 5’ cap
Influenza mRNA cal stealing
Uses cap as primer for its own mRNA
Allows translation of its viral mRNA
Reduced host protein expression
