L19 - GL Smith - Preventing and treating virus infections

Question 1

give 5 epidemiology controls for virus spreading

Answer 1

Quarantine & vaccination or slaughter

Surveillance: some diseases are notifiable

• early detection

Sanitary engineering / food hygiene regulations

• clean water & hygiene

Vector control:

• control eg mosquitos

Screening of blood and blood products

Question 2

give some exmaples (3) of targets for antiviral chemotherapy

Answer 2

• virus binding to host cell
• virus replication (n.b. enzymes)
• virus assembly or dissemination

Question 3

what do drugs ainst flu target?

Answer 3

amantadine against M2, tamiflu against NA

Question 4

Nucleoside analogues are inhibitors of…

Answer 4

Nucleoside analogues are inhibitors of virus polymerases.

Question 5

what is acyclovir active against?

Answer 5

herpes simplex virus.

Question 6

hwo does acyclovir wokr?

Answer 6

• works against HSV
• targewts viral thymidine kinase, but not cullular kinases
• The NTP is then incorporated into viral DNA by the HSV DNA polymerase, leading to chain termination. Hence ACV only works in infected cells where virus TK and DNA pol are present.

*

Question 7

describe Ganciclovir and cidofovir

Answer 7

Nucleoside analogues.

Specificity: use by virus DNA polymerase.

Used for human cytomegalovirus (HCMV) infections.

Cidofovir given intravenously and has some renal toxicity.

Question 8

Smallpox was a disease caused by …

Answer 8

Smallpox was a disease caused by variola virus.

Question 9

distinguishing features of small pox

Answer 9

Note that the skin pustules are more abundant on the face than trunk and this “centrifugal” distribution (to the outside) was a feature of smallpox that distinguished it from chickenpox.

Question 10

variolar virus mortality rates?

Answer 10

Variola major virus caused a mortality rate of 30 - 40% in unvaccinated populations. The milder variola minor virus (or alastrim) had a mortality rate of ~ 1%.

Question 11

Why was smallpox eradication possible? (6)

Answer 11

• No animal reservoir: smallpox was a human disease: contrast with rabies or yellow fever
• The infection was acute, the virus did not establish latent or persistent infection: contrast with the herpes viruses
• Smallpox was an easily recognised disease: contrast with HIV
• Vaccine worked against all virus strains: no antigenic variation: contrast with influenza
• The vaccine was potent as a single dose, low cost and abundant (self-replicating), heat stable when freeze-dried, easy to administer, induced cellular and humoral immunity
• WHO determination

Question 12

some vaccine examples

Answer 12

Eradicated: smallpox and rinderpest
Controlled: e.g. diphtheria, tetanus, pertussis, yellow fever, polio, measles, mumps, rubella Unchecked: AIDS, malaria and tuberculosis

Question 13

Today rabies vaccine is grown in cell culture and treated with _______ to inactivate virus infectivity.

Answer 13

Today rabies vaccine is grown in cell culture and treated with β-propriolactone to inactivate virus infectivity.

Question 14

describe passive immunisation

Answer 14

Question 15

describe live vaccines

Answer 15

Attenuated mutants of the virulent virus, e.g. yellow fever, measles, mumps, rubella, polio

(Sabin).

Live, related viruses. E.g. vaccinia virus for smallpox, or turkey herpes virus for Marek’s disease (tumour inducing virus of chickens).

• Advantages: self-replicating (so cheaper), induce both cellular and humoral immunity that is long lived.
• Disadvantages: the virus might revert to virulence and might cause problems in immunocompromised vaccinees. Cold storage is needed for most live vaccines.

Question 16

Contrast the pros and cons of the Salk (killed) and Sabin (live) vaccines for poliovirus.

Answer 16

Sabins live but attenuated oral vaccine that proved to be superior in administration, but also provided longer lasting immunity than the Salks killed vaccine.

Question 17

describe dead vaccines

Answer 17

Whole virus that has been inactivated (e.g. poliovirus, Salk)

Subunit vaccines containing a component of the virus derived from whole virus (e.g. influenza) or expressed by genetic engineering (e.g. HBV, HPV).

• Advantage: safety (no infectivity).
• Disadvantages: require multiple administration with adjuvant to achieve adequate level of immunity: mostly induce antibody rather than cellular immunity.

Question 18

FYI

Answer 18

Question 19

FYI 2

Answer 19

Question 20

things to consider for vaccine developement

Answer 20

Question 21

regarding vaccine devleopement, what is Rational attenuation

Answer 21

modification or deletion of a virus gene promoting virulence.

The vaccine for pseudorabies virus (a herpesvirus of pigs) is an engineered vaccine in which the thymidine kinase gene is deleted. Deletion of ExoN from SARS-CoV-2?

Question 22

regardign vaccines - what is a live recombient vaccine

Answer 22

express the gene encoding the desired antigen in a live (safe) virus vector. Example: rabies glycoprotein gene in vaccinia virus. Infection with the recombinant virus induces immunity to rabies (and smallpox).

Used to immunise the foxes against rabies in parts of Western Europe. Multiple genes from different pathogens can be engineered into the same virus to create polyvalent vaccines.

Question 23

regarding vaccines - what are Virus-like particles.

Answer 23

Synthesis of the capsid protein of some viruses can result in the production of ‘virus-like particles’. Example: vaccine against human papillomavirus 16 and 18 (that can cause cervical carcinoma).

Question 24

regarding vacciens - what is Nucleic acid immunization: Prime-boost.

Answer 24

Inject DNA encoding the antigen under a strong promoter. Boost with a live virus vector expressing the same antigen.

Question 25

look over table of viruses at the bottom of handout

Answer 25

good

Question 26

fat

Answer 26

mamba