MCB Lecture 54 Treating viruses

Question 0

Describe the kinetics of the immune response clearing viruses in the body

Answer 0

NK cells initially reduce numbers of virus
CTL further reduce numbers

Virus isn’t fully cleared until we have specific antibodies made by plasma B cells

Question 1

What are the natural ways that viral infection can be prevented or slowed?

Answer 1

1. Secreted antibody neutralisation (IgA)
2. NK cells recognise virally infected cells
3. Classical pathway
4. CD8+ kill virally infected cells
5. Phagocytosis
6. Mannose binding lectin
7. Interferon secretion by macrophages

Question 2

What is the aim of vaccination?

Answer 2

To create pools of memory cells (CTL, HTL, B cells)

Question 3

Describe the function of memory lymphocytes in clearing viruses

Answer 3

1. CTL: when virus is reintroduced, kills infected cells
2. HTL: help B cells
3. Make antibodies that neutralise virus, prevent attachment and stimulate opsonisation and lysis

Question 4

Explain the function of immune cells clearing rhinovirus.

Answer 4

Antibody binds over the groove on the capsid that normally binds to the host cell. Now, the virus can not bind to the host cell, and thus will not infect cells

Question 5

What are some of the different types of vaccine?

Answer 5

1. Live attenuated
2. Attenuated through use in a different host
3. Killed virus
4. Virus like particles
5. Broken into subunits
6. Recombinant proteins
7. Vaccine vectors

Question 6

Which types of vaccine do we have for mumps, polio, rubella and the measles?

Answer 6

Live attenuated viruses

Question 7

Which type of vaccine do we have for smallpox?

Answer 7

Attenuated through use in a different host (cow)

Question 8

Describe vaccines that have viruses attenuated due to use in a different host

Answer 8

When used in a different host, the virus changes to be more effective at killing this host
They then become less virulent in humans and can be used to create an immune response in humans because the surface molecules are the same, but they do not cause the same magnitude of disease

Question 9

Which type of vaccine do we have for polio?

Answer 9

Live attenuated, killed virus

Question 10

Which type of vaccine do we have for influenza?

Answer 10

Virus broken into subunits, the harmful parts are isolated and removed

Question 11

What type of vaccine do we have for HPV?

Answer 11

Virus like particles

Only the protein capsid, no genome, thus non virulent

Question 12

What treatment do we have for polio?

Answer 12

No treatment (antiviral drug)

Question 13

How can polio be prevented?

Answer 13

Vaccination

Question 14

What are the two vaccines for polio?

Answer 14

Salk: killed virus,vaccination by injection
Sabin: live attenuated virus is pills

Question 15

Compare the two polio vaccines

Ease of administration
Cost
Cold chain
Risk of disease
Spread to contacts
Immunodeficient people

Answer 15

Ease of administration: Sabin much easier and cheaper (oral compared to injection)
Cold chain: Sabin must be kept in cold chain because it is live, but the Salk, no
Risk of disease: Salk has no risk. Sabin, there is a 1 in 2.5 million chance of return to virulence of the attenuated virus
Spread to contacts: Sabin can be spread to contacts because there is immunity in the alimentary tract. Salk, no intestinal immunity
Immunodeficient people: Salk is completely safe, Sabin, we aren’t sure

Question 16

What is the global polio eradication campaign?

Answer 16

The WHO is trying to eradicate polio all over the world

They are using Sabin’s orally administered, live attenuated vaccine

Question 17

How do we treat viruses that have already caused disease?

Answer 17

Antiviral drugs

Question 18

What are the two types of antiviral drugs?

Answer 18

Neurominadase inhibitors

Nucleoside analogs

Question 19

Describe the basic features of antivirals

Answer 19

1. Target specific stages of viral replication

2. No broad spectrum anti virals (due to the use of host machinery)

Question 20

Describe the action of nucleoside analog antivirals with reference to a specific one

Answer 20

Acyclovir
Lacks the five membered ring with the -OH where connection are made to the next nucleotide, thus if incorporated, it will stop transcription.
However, it also lacks the phosphates, so it is not incorporated into DNA in normal cells

In virally infected cells, there is thymidine kinase (courtesy of the virus)
This enzyme adds phosphate to the acyclovir so it then becomes incorporated into DNA

DNA synthesis stops and those cells die

Question 21

Describe the action of neurominadase inhibitors

Answer 21

These block the active site of neurominadase

Now, this enzyme can no longer remove sialic acid from the membrane of the host cell, so the virus immediately binds back to the cell it is bursting out of, and for this reason, can not spread to other areas in the body

Question 22

Describe the function of neurominadase and haemoglutinin

Answer 22

Haemoglutinin: binds to sialic acid on the host membrane
Neurominadase: cleaves sialic acid so that virus does not remind when it bursts out of a host cell

Question 23

What are the two neurominadase inhibitors?

Answer 23

Ralenza (Zanamivir)

Tamiflu (oseltamivir)

Question 24

What is the outcome of the neurominadase inhibitors in terms of progression of the infection?

Answer 24

The severity and the durationof the infection is lessened

However, the drug must be taken within two days of symptoms appearing

Question 25

Describe how there can be resistance to neurominadase inhibitors

Answer 25

Some viruses can change one amino acid in the neurominadase active site, so that Ralenza can no longer bind

If this mutation is viable, it will be selected for and the resistant virus becomes more common