L8. Viruses: General Principles 2 Flashcards
Describe the viral single, one-step-growth curve in terms of the phases
- There is an initial eclipse phase where the virus doesn’t appear to be doing anything. This is where viral proteins are being synthesised. This is because viruses are not viable without assembly.
- Very large amplification of viral numbers
- The latent phase is the phase before any viral particles are found extracellularly as viruses where viral particles are released out to infect more cells.
How is the information required for viral growth curves gained?
Infect a monolayer of cells with viral particles and see plaques (areas of cell death). Also take fluid samples from the top of the monolayer for viral release.
What are the major stages of the viral replication cycle? [7]
- Attachment
- Penetration
- Uncoating
4a. Viral genome replication
4b. Viral RNA synthesis
4c. Viral protein synthesis - Assembly
- Release
- Reinfection
What is the significance about the major steps of viral genome replication and transcription?
They can occur in a number of different sequences depending on the different viruses and their genome types.
Viral particles are able to infect any type of cell in any sort of host. True or False?
This is false. Viral particles are only able to adhere to and penetrate hosts if there is specific binding to receptors on the host cell. These are specific for different organs in a host as well as for different species of hosts.
How do viral particles reach their targets?
In a purely coincidental manner. Viruses have no energy and rely on the host to move it until it eventually comes into contact with the right host.
Are receptors there purely for the purpose of viral interaction? What are some examples of receptors for viruses?
No. The host expresses receptors for their own physiological purposes. The viruses have adapted to recognise and utilise their receptors.
EXAMPLES: Proteins (ICAM for rhinovirus) and carbohydrates (sialic acid for influenza)
Explain the general process of HIV binding to two receptors and then penetration.
HIV binds to CD4 by 2 receptors. Glycoproteins gp120 to CD4. This binding event leads to a conformational change in a hydrophobic glycoprotein region to be outside the protein. This transient change allows for gp41 to bind CCR5. This initiates the melding of the two membranes that pull the apart forming a pore for genomic information to flow into the cell and into the nucleus.
What are the 2 methods of viral entry/penetration into the cell?
- Membrane Fusion: can only be done by enveloped viruses. The viral and host membranes fuse together forming a pore and this enables virus nucleocapsid directly into the cytoplasm.
- Endocytosis: can be done by both enveloped and non-enveloped viruses. The virus enters using the host’s endocytotic mechanisms in the clatherin coated pit, invagination into the intracellular vesicles.
Explain the penetrating mechanism of Togavirus.
It binds to a receptor molecule that triggers endocytosis by a clatherin coated pit that pinches into an endosome in the cell. Release from the endosome is triggered by a change in pH to acidic including a conformational change that releases the virus.
Describe the uncoating process
The viral genome is released from the protective capsid to be transported into the cell. It isn’t completely known: likely an induced change in shape of the virus enabling toxicity that breaks the endosome down.
What is the aim of nucleic acid replication?
To produces new viral genomes to be incorporated into new progeny viruses.
What is the general trend for viral replication sits?
DNA viruses tend to replicate in the nucleus while RNA in the cytoplasm. The exceptions being influenza, poxvirus and HIV.
How are the mRNA genomes transcribed into proteins?
Done by host cell mechanisms
What type of polymerase is required for replication of some RNA genomes?
RNA-dependent-RNA-polymerases which is not provided by the host cell
How do positive ssRNA transcribe their genome?
Positive sense ssRNA is the same genomic structure mRNA and so the host is able to read and transcribe the whole mRNA.
The mRNA autocleaves itself into functional units one of which is protease that recognises itself to cleave further and more specifically. Out of these comes an RNA-dependent-RNA polymerase that synthesises more of the genome to amplify the process.
How do negative ssRNA transcribe their genome?
These strands are complimentary to mRNA and cannot use host mechanisms. Thus these genomes carry their own RNA-dependent RNA polymerase but also encode it to amplify the process.
What is the Baltimore Classification?
A classification of the way DNA viruses produce mRNA from their genome.
Most DNA viruses don’t carry polymerases because the host can read it. Except pox and hepadna
Positive strands don’t carry it (except HIV)
Negative strands always carry it
Describe the translation and the post-translational protein processing functions?
Host ribosomes are used to translate viral proteins. Post translational cleavage of the proteins usually requires VIRAL-CODED PROTEASES.
How is the process of glycosylation done?
Glycosylation of the envelope occurs in the rER and golgi which primes them for transport to deposit on the cell surface.
What structure do all non-enveloped viruses have? What is significant about this shape?
An icosahedral structure. Capsomers are ENERGY MINIMISED in this form and so want to spontaneously form this structure.
There are multiple different ways for icosahedral structure assembly. Describe one major method.
There is a spontaneous need to form the icosahedral structure and this spontaneous forming traps the genetic material inside it. Proteolytic cleavage to induce the final, stable conformation is often required.
How do the non-enveloped viruses release out of the cell?
They accumulate in the cytoplasm or nucleus and only release when the cell lyses.
How do most enveloped viruses get assembled in and then released out of the the cell?
Budding.
Patches of viral envelope glycoproteins accumulate in a section of the plasma membrane and cause the viral proteins and genome to accumulate and condense around this point.
The membrane bulges out and nips forming a new enveloped virion.