Virology Flashcards
What are viruses?
Infectious obligate intracellular parasite
Have nucleic acid based genome which replicates in host cell
What is the central dogma?
‘Central Dogma’ is the process by which the instructions in DNA are converted into a functional product
- DNA –> RNA –> Protein
- some virses have RNA genomes and never used DNA, some convert
- RNA –> DNA ( reverse transcriptase )
Describe virus morphology?
Can be:
- symmetrical protein capsid ( adenovirus, calicivirus ) non enveloped
- enveloped (lipid) ( measles, ebola )
What leads to viral high mutation rate?
RNA viruses and retroviruses use their own polymerase to replicate = lack proof reading capacity meaning high mutation rate
Differences between RNA viral and DNA viral genomes?
RNA viral genomes are limited in size due to instability, 30 kb, RNA virses often use complex coding strategies to make more proteins than expected
DNA have 100s kb,
What are genome segments?
Segmented genomes allow recombination knowns as reassortment
- can mix themselves up if 2 viruses are in the same cell = new strains
How do virus replicate?
- Virus attached to glycoprotein and enters
- Capsid falls away
- Genome replicated and converted to mRNA unless already mRNA itself
- Replicate with polymerase
Assembles and is expelled
Viral replication cycle of HIV?
… check diagram
Influenza viral replication cycle?
… check diagram
What is a cytopathic effect?
Death of cell by virus, can be shut down of host protein or accumulation of viral proteins
Viruses form x in cell monolayers?
Plaques
Plaque assay : use dilutions and putting virus in cell layers, counting plaques
- some viruses do not cause plaques
What are syncytia?
( HIV ) have surface proteins that fuse cells together at pH7
How can you diagnose virses?
- DNA PCR
- ELISA
- Electron microscopy
- Cytopathic effect
- Serology
How can we manipulate viruses?
Viral genomes synthesised and introduced to a cell , will replicate
Can introduce mutations and engineer genomes : vaccines
What can antiviral drugs do?
Target viral factors
Others act as nucleoside analogues to inhibit with nucleic acid replication
What is Acyclovir used for?
HSV
Chicken pix
How does Acyclovir work?
Chain terminator to prevent viral DNA synthesis:
converted to acyclovir triphosphate in HDV cells due to the thymidine kinase present,
Acyclovir triphosphate –> inhibits DNA synthesis
What is Remdesivir?
( active against coronavirus )
Analogue of Adenosine - chain termination 3 nucleotides downstream of incorporation, = twists shape of molecule
Why do antiviral drugs have to be very specific?
Viruses evolve very quickly
o Viruses = obligate intracellular parasites
o Outside completely inert –> can’t do anything
o Genome can be made of DNA or RNA
o Inside cell virus replicates its genome
o Has to co-opt cellular machinery existing inside cell
o Have to find things which are unique to viruses to target like with antibiotics
What is prophylaxis?
Preventing disease before cause is acquired - vaccination
What is Amantadine/Rimantadine?
Used against influenza
Cyclic amines which can have bulky cage like structures
Byproducts of petroleum refinement
How does Amantadine/Rimantadine? work?
Block replication of influenza
§ M2 protein - tetrameric ion channel involved in uncoating of virus - drug blocks this ion channel so protons can’t get through and unlock viral core
§ Virus locked in endosomes and won’t initiate infection
§ Single amino acid change in M2 can make virus resistant e.g. Serine to asparagine @ position no. 31, amino acid 31 (S31N mutation has little/no cost to fitness of virus)
How do Neuraminidase inhibitors work?
Neuroaminidase is important to virus, without it the virion would stick back to sialic acid receptor on the infected cell surface
Neuroaminidase cleaves this apart, halting it would halt virus replication
Examples of Neuroaminidases?
Sialic acid
Relenza
Tamiflu
What is Baloxavir?
Inhibits the polymerase acidic endonuclease = targeting polymerase
- resistance present to this, PA protein can accumulate due to point mutation
How is Hep C treated?
Injection therapy replaced with drugs that can eliminate the virus
What type of HIV antivirals are present?
- Inhibit viral entry
- Fusion inhibitors stop virus envelope fusing with plasma membrane
- Reverse transcriptase inhibitors
- Protease inhibitors
What combination therapy is used for HIV?
AZT/zidovudine - nuceloside analogue
How does combination therapy work?
You have a drug, which targets a single place on HIV genome, 10,000 nucleotides long with a reverse transcriptase error rate 1 in every 10,000.
§ It’s only going to take one round of replication for the virus to generate the mutation which escapes your drug. But that same genome has another target here,
§ for a second drug.
§ The chances that that genome generate the mutation to your first drug and the mutation to your second drug in the given time, very slim.
§ Now, if you target a different gene of the virus with a third drug that requires a third mutation, the chances that one genome gets all three, very slim.
§ Of course, you’ll get one or the other or the other. But so long as you’re taking all the drugs at once, each singly changed one can’t escape
