Treatment of Viruses

Question 1

how does virus replicate?

Answer 1

Varies with each virus but here are the main steps:

Attachment
Entry
Uncoating
mRNA made
Protein synthesis
Virion assembly
Release

Question 2

what do the following do with rna ?

Reverse transcriptase

Integrase

Protease

RNA polymerase

Answer 2

Reverse transcriptase – turns +ssRNA into DNA

Integrase – integrates viral DNA with host genome

Protease – help create viral building blocks

RNA polymerase – forms mRNA before going to ribosome

Question 3

how does viral evasion of host defence occur?

Answer 3

Latency: Dormancy that reactivates when host is immunocompromised e.g. HIV, Herpes
Phagocyte evasion:Prevention of phagosome and lysosome fusione.g. HIV
Antigenic shift and drift: Genetic shuffling and random mutation makes immune system naïve again
Hiding: Within cells: HSV, VZV, malaria

Question 4

basic ways can prevent viral infection?

Answer 4

• hand hygeine
• *- cover cough
• environmental cleaning:**1:10 bleach solution. EPA registered disinfectant
• PPE

Question 5

how do viral vaccines work? (basic)

Answer 5

viral vaccines: induced a immune repsonse agaisnt viruses in the vaccinated people - helps immune system tofight off future infections. gives immune memory:

• *immune memory:**
• rapid increase in response
• response is faster

Question 6

what does % of individuals needing to be immunised to acheive herd immunity depend on?

Answer 6

• effectiveness of vaccine
• characterisitcs of disease

herd immunity creates barriers that protects susceptible people

Question 7

what is herd immunity?

Answer 7

Indirect protection of susceptible individuals from infectious disease when certain percentage of population (normally 95%) has become immune to the disease

Question 8

what is herd immunity threshold?

R_o ​= ?
1/ Ro = ?
R_o < 1 ?
R_o > 1 ?

1-1/R_o ?

Answer 8

R_o = av. number of new transmissions per case over infectious period in sus or non vaccinated pop
1/ Ro = proportion of the population sus. to virus (aka epidemic threshold)
R_o < 1 infection dies out
R_o > 1 infection will spread
R_o = 1 infection stable

proportion of pop. that needs to be vaccinated to eliminate virus: 1-1/R_o

Question 9

how do you work out what proportion of population needs to be vaccinated?

Answer 9

1 - Goal Ro / Current Ro

(goal Ro is 1)

e.g. measles has Ro of 18. so to work out pop that needs to be vaccinated:

1-1/18

= 1 - 0.06

= 94%

Question 10

if proportion of susceptible individuals is recuded to below X, the diease can be eradicated. what is X?

Answer 10

1/Ro

Question 11

what are different ways can make viral vaccines?

Answer 11

• live attenuated virus (virus is weakend by chemicals or heat inactivation
• recombinant sub-unit viral protein: part of o.g. virus presented to immune
• recombinat bacterial vector (take genes of virus and put in bacteria)
• virus-like particles (look like viruses but dont have pathogen inside, just immunogenic regions required)
• DNA (inject viral DNA into muscle)
• *- recombinant viral vector:** (put spike protein into non infectious viral vector, e.g. cold )
• **synthetic peptides
• whole inactivated virus**

Question 12

how do inactiavted vaccines work?

e.g.?

how long does immunity last?

Answer 12

• destroy infectivity but keep the ability to induce immune response (keeps antigenicity)
• e.g. poliovirus, influenza
• immunity is often brief: requires boosting

Question 13

how do live attenuated vaccines work? e.g.?

who cant we give to?

Answer 13

Live vaccines use a weakened (or attenuated) form of the germ that causes a disease.

• long response
• replication competent but dont cause disease.
• e.g. measles, oral polio
• **cant use in immunodeficient patients
• risk of reversion**

Question 14

subunit vaccines / virus like particles?

e.g. ?

Answer 14

• break up virus into fragments (like its protein, sugar, or capsid)
• resemble structure of the virus
• **no genetic information: safe
• **cost-effective
• e.g. HPV and HBV

Question 15

dna vaccine?

Answer 15

no approved vaccines yet!

• naked DNA
• does not replicate in viral host
• go into muscle or skin
• long lasting
• dry powder (dont need to fridge)

Question 16

how can antivirals target viruses?

Answer 16

Targets viral replication process:

• Reverse transcriptase: RNA to DNA

• Integrase: integration of viral genetic material into host genome
• Protease: cleave precursor proteins

Question 17

what % of pop. needs to be vaccinated for measles?

Answer 17

95%

Question 18

why are there so few antivirals?

Answer 18

• the virus life cycle is tied to host cell: difficult to target virus alone
• viruses are difficult to grow
• most virus infections are short lived
• *- compound must block virus replication compelely otherwise the virus will mutate and become resistant**

Question 19

what is herpesvirus?

how work?

Answer 19

• dsDNA viruses
• stays latent in body after infection:
• *- chickepon infection:** virus goes into dorsal root ganglia and stays latent and can reemrge later in life as shingles

Question 20

which antivirals do we use for chickenpox and herpes? whats the mechnaism of action?

Answer 20

• *acyclovir**:
• reduces symptoms but doesnt cure
• mimics one of the 4 bases for DNA (but misses OH group): **terminates DNA sythesis
• **prodrug mechanism:
• has to be activated by HSV enzyme thymdine kinase to add P
• cellular kinases add 2nd and 3rd P
• chain termiantes
• can get resistance
• need to treat IC patients

Question 21

how do HIV ARV works?

Answer 21

drugs: HAART (highly active ART)

Uses a variety of inhibitors in from different classes of anti-viral drugs to reduce the viral load.

• Entry inhibitors
• Reverse transcriptase inhibitors (NRTI, NNRTI)
• Integrase inhibitors
• Protease inhibitors
• Fusion inhibitors

Question 22

hiv lifecyle?

Answer 22

The seven stages of the HIV life cycle are: 1) binding, 2) fusion, 3) reverse transcription, 4) integration, 5) replication, 6) assembly, and 7) budding.

Binding and fusion (attachment)

• HIV attaches to a T-helper cell. It then fuses to it and releases its genetic information into the cell.*
• The types of drugs that stop this stage of the lifecycle are called fusion or entry inhibitor drugs – because they stop HIV from entering the cell.*

Reverse transcription (conversion) and integration

• Once inside the T-helper cell, HIV converts its genetic material into HIV DNA, a process called reverse transcription. The new HIV DNA then enters the nucleus of the host cell and takes control of it.*
• The types of drugs that stop this stage of the lifecycle are called NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors) and integrase inhibitor drugs.*

Transcription and translation (replication)

The infected T-helper cell then produces HIV proteins that are used to produce more HIV particles inside the cell.

Assembly, budding and maturation

• The new HIV is put together and then released from the T-helper cell into the bloodstream to infect other cells; and so the process begins again.*
• The type of drugs that stop this stage of the lifecycle are called protease inhibitor (PI) drugs.*

Question 23

what is HIV mutation like? why important?

Answer 23

mutates rapidly! use specific targeting of combination therapy: makes it hard for virus to mutate to all of the stages of viral life cycle

Question 24

what are the different types of viral mutations that occur?

Answer 24

Antigenic shift: combination of different viral RNA in the host cell to produce a new variant

Antigenic drift: accumulation of random mutations during viral replication