Virology

Question 1

What are viruses?

Answer 1

Infectious obligate intracellular parasite

Have nucleic acid based genome which replicates in host cell

Question 2

What is the central dogma?

Answer 2

‘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 )

Question 3

Describe virus morphology?

Answer 3

Can be:

• symmetrical protein capsid ( adenovirus, calicivirus ) non enveloped
• enveloped (lipid) ( measles, ebola )

Question 4

What leads to viral high mutation rate?

Answer 4

RNA viruses and retroviruses use their own polymerase to replicate = lack proof reading capacity meaning high mutation rate

Question 5

Differences between RNA viral and DNA viral genomes?

Answer 5

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,

Question 6

What are genome segments?

Answer 6

Segmented genomes allow recombination knowns as reassortment

• can mix themselves up if 2 viruses are in the same cell = new strains

Question 7

How do virus replicate?

Answer 7

• 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

Question 8

Viral replication cycle of HIV?

Answer 8

… check diagram

Question 9

Influenza viral replication cycle?

Answer 9

… check diagram

Question 10

What is a cytopathic effect?

Answer 10

Death of cell by virus, can be shut down of host protein or accumulation of viral proteins

Question 11

Viruses form x in cell monolayers?

Answer 11

Plaques

Plaque assay : use dilutions and putting virus in cell layers, counting plaques

• some viruses do not cause plaques

Question 12

What are syncytia?

Answer 12

( HIV ) have surface proteins that fuse cells together at pH7

Question 13

How can you diagnose virses?

Answer 13

• DNA PCR
• ELISA
• Electron microscopy
• Cytopathic effect
• Serology

Question 14

How can we manipulate viruses?

Answer 14

Viral genomes synthesised and introduced to a cell , will replicate

Can introduce mutations and engineer genomes : vaccines

Question 15

What can antiviral drugs do?

Answer 15

Target viral factors

Others act as nucleoside analogues to inhibit with nucleic acid replication

Question 16

What is Acyclovir used for?

Answer 16

HSV

Chicken pix

Question 17

How does Acyclovir work?

Answer 17

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

Question 18

What is Remdesivir?

Answer 18

( active against coronavirus )

Analogue of Adenosine - chain termination 3 nucleotides downstream of incorporation, = twists shape of molecule

Question 19

Why do antiviral drugs have to be very specific?

Answer 19

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

Question 20

What is prophylaxis?

Answer 20

Preventing disease before cause is acquired - vaccination

Question 21

What is Amantadine/Rimantadine?

Answer 21

Used against influenza

Cyclic amines which can have bulky cage like structures

Byproducts of petroleum refinement

Question 22

How does Amantadine/Rimantadine? work?

Answer 22

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)

Question 23

How do Neuraminidase inhibitors work?

Answer 23

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

Question 24

Examples of Neuroaminidases?

Answer 24

Sialic acid

Relenza

Tamiflu

Question 25

What is Baloxavir?

Answer 25

Inhibits the polymerase acidic endonuclease = targeting polymerase * resistance present to this, PA protein can accumulate due to point mutation

Question 26

How is Hep C treated?

Answer 26

Injection therapy replaced with drugs that can eliminate the virus

Question 27

What type of HIV antivirals are present?

Answer 27

- Inhibit viral entry - Fusion inhibitors stop virus envelope fusing with plasma membrane - Reverse transcriptase inhibitors - Protease inhibitors

Question 28

What combination therapy is used for HIV?

Answer 28

AZT/zidovudine - nuceloside analogue

Question 29

How does combination therapy work?

Answer 29

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