MCB Lecture 54 Treating viruses Flashcards
Describe the kinetics of the immune response clearing viruses in the body
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
What are the natural ways that viral infection can be prevented or slowed?
- Secreted antibody neutralisation (IgA)
- NK cells recognise virally infected cells
- Classical pathway
- CD8+ kill virally infected cells
- Phagocytosis
- Mannose binding lectin
- Interferon secretion by macrophages
What is the aim of vaccination?
To create pools of memory cells (CTL, HTL, B cells)
Describe the function of memory lymphocytes in clearing viruses
- CTL: when virus is reintroduced, kills infected cells
- HTL: help B cells
- Make antibodies that neutralise virus, prevent attachment and stimulate opsonisation and lysis
Explain the function of immune cells clearing rhinovirus.
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
What are some of the different types of vaccine?
- Live attenuated
- Attenuated through use in a different host
- Killed virus
- Virus like particles
- Broken into subunits
- Recombinant proteins
- Vaccine vectors
Which types of vaccine do we have for mumps, polio, rubella and the measles?
Live attenuated viruses
Which type of vaccine do we have for smallpox?
Attenuated through use in a different host (cow)
Describe vaccines that have viruses attenuated due to use in a different host
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
Which type of vaccine do we have for polio?
Live attenuated, killed virus
Which type of vaccine do we have for influenza?
Virus broken into subunits, the harmful parts are isolated and removed
What type of vaccine do we have for HPV?
Virus like particles
Only the protein capsid, no genome, thus non virulent
What treatment do we have for polio?
No treatment (antiviral drug)
How can polio be prevented?
Vaccination
What are the two vaccines for polio?
Salk: killed virus,vaccination by injection
Sabin: live attenuated virus is pills
Compare the two polio vaccines
Ease of administration Cost Cold chain Risk of disease Spread to contacts Immunodeficient people
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
What is the global polio eradication campaign?
The WHO is trying to eradicate polio all over the world
They are using Sabin’s orally administered, live attenuated vaccine
How do we treat viruses that have already caused disease?
Antiviral drugs
What are the two types of antiviral drugs?
Neurominadase inhibitors
Nucleoside analogs
Describe the basic features of antivirals
- Target specific stages of viral replication
2. No broad spectrum anti virals (due to the use of host machinery)
Describe the action of nucleoside analog antivirals with reference to a specific one
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
Describe the action of neurominadase inhibitors
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
Describe the function of neurominadase and haemoglutinin
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
What are the two neurominadase inhibitors?
Ralenza (Zanamivir)
Tamiflu (oseltamivir)
What is the outcome of the neurominadase inhibitors in terms of progression of the infection?
The severity and the durationof the infection is lessened
However, the drug must be taken within two days of symptoms appearing
Describe how there can be resistance to neurominadase inhibitors
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