6 Prevention and Treatment of Viral Disease Flashcards

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1
Q

*Q: What is prophylaxis?

A

A: preventing disease before the aetiologic agent is acquired, by vaccination or giving drug before infection

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2
Q

*Q: What is therapy?

A

A: treating the disease after the host has been infected

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3
Q

Q: What do vaccines try and do?

A

A: replace the first infection with a vaccine to generate antibody production without having pathological effects

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4
Q

Q: What can the presence of antibodies in the serum show? used for?

A

A: used for diagnosis as it shows that there was an infection at one point

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5
Q

Q: Give 2 examples of successful virus vaccination?

A

A: polio, smallpox

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6
Q

*Q: Give 2 reasons why smallbox was successfully vaccinated against.

A

A: no animal reservoir

easily see who has smallpox allowing you to work out who they’ve come into contact with

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7
Q

*Q: Name 4 types of viral vaccines. Which was used against smallpox?

A

A: -live attenuated eg small pox

  • inactivated
  • purified subunit
  • cloning
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8
Q

*Q: Describe live attenuated viral vaccines. Examples? (8)

A

A: natural virus with its genome inside the capsid which has had its virulence reduced so it only produces a mild infection and kick starts the immune response

  • adenovirus
  • influenza
  • measles
  • mumps
  • polio
  • rubella
  • smallpox
  • varicella
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9
Q

*Q: Describe inactivated viral vaccines. Problem? solution? Examples? (4)

A

A: -take the parental virus and treat it with chemicals and heat to destroy the genome so it is no longer infectious
-> injected into a person, the viral proteins will still be recognised and an immune response will be triggered

Getting an immune response from this vaccine is more difficult so you may need to add adjuvants

  • hepatitis A
  • polio
  • rabies
  • encephalitis
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10
Q

Q: Describe purified subunit viral vaccines. Example?

A

A: Original parental genome has been taken and treated with proteases to chop it into little pieces

These are subunits of the virus which contains antigens that can trigger an immune response

-influenza

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11
Q

Q: Describe ‘cloning’ viral vaccines. Options? (3) Examples? (2)

A

A: -Parts of the original viral genome are cloned inside bacteria

  • can put the DNA into virus-like particles (e.g. HPV vaccine) = Virus-like particle vaccine
  • may just inject viral DNA into people = DNA vaccine
  • may make a new virus which doesn’t make people ill but has a segment of virulent material from the original virus
  • hepatitis B
  • human papillomavirus
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12
Q

Q: How do you make live viral vaccines? (5 steps) Theory?

A

A: attenuation

  1. Isolate pathogenic virus from patient
  2. Grow in human cells
  3. Take cultured virus and infect monkey cells
  4. Gradually the genome of the virus will adapt to the monkey cells and it will become a monkey virus
  5. The virus will no longer grow well in human cells

Take a virus and pass it through the wrong cell/wrong species - you will make the virus evolve so it is no longer virulent to humans

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13
Q

*Q: Pros and cons of live vaccines? (3,2)

A

A: -rapid broad, long lived immunity

  • dose sparing
  • cellular immunity
  • requires attenuation
  • may revert
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14
Q

*Q: Pros and cons of inactivated vaccines?

A

A: -safe
-can be made from wild type viruses

  • frequent boosting required
  • high doses needed
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15
Q

*Q: Name 2 viruses for which both live and inactivated vaccines are available.

A

A: influenza, poliovirus

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16
Q

Q: What are the 2 options for influenza vaccines? consists of? Who’s given it? (2) Updates?

A

A: Inactivated vaccine or the subunit vaccine consists only of the spike proteins (HA)

people are risk - e.g. over 65, asthmatics, diabetes, CVD and healthcare workers

vaccines must be updated regularly become influenza evolves fast

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17
Q

Q: What’s the new strategy of influenza vaccination for children? (3)

A

A: Live Attenuated Influenza Vaccine

Cold Adapted - can replicate at 32 degrees (nose) but not at 37 degrees

Given as a nasal spray

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18
Q

Q: What are the 2 options for poliovirus vaccines? Describe both including downside (2,2). End game?

A

A: SALK inactivated vaccine

  • Preparation of virus which has been treated so it can no longer replicate
  • Isn’t a particularly good vaccine - need a large dose

SABINE live attenuated vaccine

  • better
  • If this vaccine was given to people who are immunosuppressed they get a PERSISTING INFECTION - they are reservoirs of live polio virus

must stop using Sabine and switch to Salk for the end game

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19
Q

Q: How do you make recombinant attenuated virus vaccines? (3) Example?

A

A: Pathogenic virus genome typically consists of receptor-binding gene, virulence gene and capsid protein genes

You can either mutate the virulence gene or delete the virulence gene

You then get a virus which is IMMUNOGENIC but NOT VIRULENT

rotavirus vaccine

20
Q

Q: What is the rotavirus vaccine an example of? Used for? reason?

A

A: live attenuated rotavirus reassortant vaccine

only given to babies <15 weeks -> Early use of the vaccine in the US showed that it can cause intussusception (bowel blockage) in older babies (>3 months)

21
Q

Q: What is shingles? Affects mainly? Even after rash has gone, what can happen? Vaccine? similar to? Available to?

A

A: -Painful rash resulting from reactivation of varicella zoster virus infection

  • More common and serious in elderly as their immune system wanes
  • pain could remain as Post Herpetic Neuralgia (PHN)
  • live attenuated
  • similar but distinct from the chicken pox vaccine given to children in some countries
  • Shingles vaccine introduced in September 2013 but only available to people 70-79 years
22
Q

Q: What was used in the Thai Trial RV-144 to test HIV vaccine? Method? After primary immunisation? Efficiency?

A

A: -Canary pox virus (affects canaries) vector used

  • Fragments of HIV antigens inserted into vector
  • After primary immunisation, recipients received a booster consisting of gp120

38% efficacy - better than anything before

23
Q

Q: Antiviral treatment option? (2) Alternative?

A

A: isn’t a general/broad acting drug like antibiotics that can be given for viruses
-Nearest alternative = Interferons

Alternatively - you treat symptomatically

24
Q

Q: How do interferons work in terms of antiviral treatmement? Problem? (2)

A

A: switch on a natural antiviral response

  • Problem with Interferons: switches on everything including inflammation and fever
  • By giving interferons -> you would suppress the virus but you would make the patient feel even worse
25
Q

Q: Why is it difficult to target bacteria? What do antiviral drugs tend to target? how?

A

A: Viruses don’t have as many distinctive features as bacteria which we can target
-There isn’t very much that is UNIQUE to a virus

VIRAL ENZYMES - often by acting as SUBSTATE ANALOGUES

26
Q

Q: What are nucleoside analogues? How do they work?

A

A: Best antiviral that we have

Viruses have to replicate their genome at some point - hence they have to add nucleotides or nucleosides to their growing RNA chain -> nucleoside analogues work via chain termination as they look like normal bases but have a little bit missing

27
Q

Q: How do nucleoside analogues cause chain termination?

A

A: The modified nucleosides are incorporated into the DNA

Lack of a 3’ hydroxyl group (the part which the next nucleotide usually attaches onto) means that the chain terminates and a phosphodiester bond isn’t formed

28
Q

*Q: What is acyclovir? Why is it good? Similar to? How do you administer? What can act on it and how?

A

A: Very good antiviral -> specific to virus infected cells (has a higher affinity for Viral DNA polymerase than host DNA polymerase)

looks like guanosine but is completely missing the bottom half of the ring

administer it as the pro-drug

can only be phosphorylated by virus encoded enzyme - THYMIDINE KINASE

29
Q

Q: What are the 2 strategies to inhibit influenza?

A

A: Inhibition of M2 Channel

Neuraminidase

30
Q

Q: In terms of influenza, how do you activate the M2 channel? Function? (4) What happens if blocked? (2) What can block them?

A

A: Low pH inside the endosome activates the M2 channel

Activation and opening of M2 channel on virus capsid allows protons to move into the virus and undo the bonds holding the capsid together -> allows uncoating of the virus and the release of its contents into the host cell cytoplasm

If M2 is blocked, the virus will remain locked in its own shell and wont gain access to the host cell’s genetic machinery

ADAMANTANES

31
Q

Q: Give 2 examples of adamantanes. What are they? Function? Downside? Current situation?

A

A: Amantadine and Rimantadine

Cyclic amines - by-products of petrol refinement

It is the right shape to fit in the M2 channel and get wedged in there so it stops protons from flowing through the M2 channel

HOWEVER, a single point mutation in the virus genome will mean that amantadine and rimantadine no longer fit in the M2 channel

Now, all strains of human influenza are amantadine resistant

32
Q

Q: What produces neuraminidase? How can inhibiting it stop the spread of infection? (5)

A

A: influenza virus

  • Virus enters the cell by binding to sialic acid
  • During infection and replication, the host cell gradually dies
  • New viruses leave the cell and want to move onto new healthier cells
  • So, virus produces neuraminidase which moves to the cell surface and destroys sialic acid so the original cell is less likely to get infected by the daughter viruses
  • IF WE INHIBIT NEURAMINIDASE - the enzymes will latch back down to the old cell and will not spread so the infection will be contained within the patient
33
Q

Q: Name 2 neueaminidase inhibitors. Method?

A

A: -Zanamivir (Relenza)
-Oseltamivir (Tamiflu)

sits in the neuraminidase binding pocket and acts as an inhibitor

34
Q

Q: List the possible targets for HIV treatment in the HIV life cycle. (5)

A

A: -NRTI (Nucleoside Reverse Transcriptase Inhibitor)

  • NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitor)
  • Integrase Inhibitor
  • Entry Inhibitor
  • Protease Inhibitor
35
Q

*Q: Name 2 examples of NRTI.

Name 2 examples of NNRTI. Method?

Name 1 integrase inhibitor.

Name 2 entry inhibitors. Include what each one does.

Name 1 protease inhibitor. (taken with)

A

A: HIV treatment:

Nucleoside Reverse Transcriptase Inhibitor

  • Zidovudine
  • Stavudine

Non-nucleoside Reverse Transcriptase Inhibitor
-Efavirenz
-Viramune
Binds enzymes but not at the active site

Raltegravir

HIV treatment
Maraviroc - blocks gp120 - CXCR4 interaction
Enfuvirtide - binds gp41 - prevents membrane fusion

Atazanavir (taken with Ritonavir)

36
Q

Q: What is HCV? What is NS3-4A?

A

A: hepatotropic flavivirus

virally encoded protease that processes the polyprotein

37
Q

Q: How did we used to treat hepatitis C? 2 first generation examples. Results?

A

A: protease inhibitors

First generation protease inhibitors were telaprivir and boceprivir

  • monotherapy results in rapid resistance
  • successfully with interferon and ribavirin
38
Q

Q: Name 2 new hepatitis C targets. How have these structures been solved?

A

A: -NS5B is the viral polymerase that replicates the RNA genome
-NS5A is the phosphoprotein required by the virus for replication

using crystallography allowing rational based drug design for Directly Acting Antivirals (DAA)

39
Q

Q: What does new hepatitis C therapy combine? (3)

A

A: Protease Inhibitor - asunaprevir

NS5A inhibitor - daclastivir

With or without: IFN and RBVN

40
Q

Q: What is Sustained Virological Response (SVR)?

A

A: not only are the patients feeling better, their viral load is going down

41
Q

Q: In the UK we currently vaccinate against the following viruses:

  1. rotavirus, poliovirus MMR, influenza
  2. rotavirus, poliovirus, MMR, chicken pox
  3. miningitis, rotavirus, MMR, yellow fever
  4. poliovirus, smallpox, rotavirus, MMR, influenza
A

A: 1. rotavirus, poliovirus MMR, influenza

42
Q

Q: All of the vaccines we currently give people in the UK to protect against viruses are:

  1. live attenuated viral vaccines
  2. given to children
  3. available for purchase in supermarkets as well as through the GP
  4. given as injections to the arm
A

A: none

43
Q

Q: Which of the following antiviral drugs are virus pairs are wrongly paired?

  1. herpes simplex virus and acyclovir (zovirax)
  2. HIV and zidovudine (NRTI)
  3. influenza and oseltamivir (tamiflu)
  4. hepatitis C and amantadine
A

A: 4. hepatitis C and amantadine

44
Q

Q: To treat HIV a combination of different drugs known as HAART (highly active antiviral therapy) is used because:

  1. it makes more money for the primary pharmaceutical industry
  2. it avoids breaching patents when giving drugs in Africa
  3. the reverse transcriptase of the virus is so error prone that virus resistance to a single drug emerges rapidly
  4. side effects of the directly acting antivirals are so severe that patients require that other drugs are given to alleviate the adverse effects
A

A: 3. the reverse transcriptase of the virus is so error prone that virus resistance to a single drug emerges rapidly

45
Q

Q: Why is it difficult to develop drugs which selectively act against viral infections?

A

A: because they’re intracellular obligate parasites = difficult to combat with chemotherapeutic agents

-> difficult to target a stage of the replication cycle that doesn’t involve host function