L19 - GL Smith - Preventing and treating virus infections Flashcards
give 5 epidemiology controls for virus spreading
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
give some exmaples (3) of targets for antiviral chemotherapy
- virus binding to host cell
- virus replication (n.b. enzymes)
- virus assembly or dissemination
what do drugs ainst flu target?
amantadine against M2, tamiflu against NA
Nucleoside analogues are inhibitors of…
Nucleoside analogues are inhibitors of virus polymerases.
what is acyclovir active against?
herpes simplex virus.
hwo does acyclovir wokr?
- 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.
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describe Ganciclovir and cidofovir
Nucleoside analogues.
Specificity: use by virus DNA polymerase.
Used for human cytomegalovirus (HCMV) infections.
Cidofovir given intravenously and has some renal toxicity.
Smallpox was a disease caused by …
Smallpox was a disease caused by variola virus.
distinguishing features of small pox
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.
variolar virus mortality rates?
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%.
Why was smallpox eradication possible? (6)
- 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
some vaccine examples
Eradicated: smallpox and rinderpest
Controlled: e.g. diphtheria, tetanus, pertussis, yellow fever, polio, measles, mumps, rubella Unchecked: AIDS, malaria and tuberculosis
Today rabies vaccine is grown in cell culture and treated with _______ to inactivate virus infectivity.
Today rabies vaccine is grown in cell culture and treated with β-propriolactone to inactivate virus infectivity.
describe passive immunisation
describe live vaccines
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.
Contrast the pros and cons of the Salk (killed) and Sabin (live) vaccines for poliovirus.
Sabins live but attenuated oral vaccine that proved to be superior in administration, but also provided longer lasting immunity than the Salks killed vaccine.
describe dead vaccines
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.
FYI
FYI 2
things to consider for vaccine developement
regarding vaccine devleopement, what is Rational attenuation
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?
regardign vaccines - what is a live recombient vaccine
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.
regarding vaccines - what are Virus-like particles.
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).
regarding vacciens - what is Nucleic acid immunization: Prime-boost.
Inject DNA encoding the antigen under a strong promoter. Boost with a live virus vector expressing the same antigen.
look over table of viruses at the bottom of handout
good
fat
mamba
